JPS60335B2 - Production method for new organic compounds - Google Patents

Description

[Detailed description of the invention]

This invention relates to a method for producing a novel aryloxy fatty acid and its alkyl ester. In particular, this invention relates to halocyclopropyl-substituted phenoxyalkanoic acids and lower alkyl esters thereof. The compounds of this invention have the general formula: (wherein R is day or C, ~6 alkyl group;
are respectively C, ~3 alkyl groups; Q is day, a halogen atom, or a C, ~3 alkyl group; RI is day, C, ~3
an alkyl group or a phenyl group; R2 and R2' are each a day or a halogen atom, and at least one is a halogen atom; R3 is a day, a C, ~3 alkyl group, or a phenyl group; R3' is a day, or a C, ~3 alkyl group; and n is an integer 0. )have. Further included within the scope of this invention are pharmacologically acceptable basic salts of the compounds in the above formula where R is day.
In the above definition, the alkyl group may be linear or branched, and the halogen atoms include four types of halogen atoms, F, CI, and B.
It means both r and 1. Preferred pharmacologically acceptable salts include sodium salts, calcium salts, magnesium salts, ammonium salts, and low toxicity organic amine salts (eg, jetanolamine salts and N-methylglucamine salts). The compound of formula 1 is obtained by converting the compound of formula
2' is as defined above. ); if desired, hydrolyze the product compound in which R is a lower alkyl group to produce a compound in which R is day; and if desired, the product compound in which R is day; It can be produced by a process consisting of converting it into its basic salt. The above equations are given in the following figure which illustrates the individual reaction equations involved in the general method described above. Skin (R is a lower alkyl group) K (R is a lower alkyl group) 1 (R is a lower alkyl group) X (R is a lower alkyl group) In the above method, the formula (In the formula, R3, R3', and Q are as defined above.) The alkanoyl-substituted phenol of chloroform, ketone A-CO-A' (wherein A and A' are as defined above), and an alkali A compound in which R is a hydrogen atom is esterified with a lower alkanol, or a compound in which R is a hydrogen atom is esterified with a mixture of a metal hydroxide and a metal hydroxide. (
In the formula, A and A' are as defined above, and R is C, a central lower alkyl group. ). In the manner described above, a compound in which R is a lower alkyl group in the formula can be obtained. The next step is to convert the alkanoyl-substituted phenoxyalkanoic acid ester of the formula into borohydride, alkali metal hydride, and halogenated RI.
From treatment with Mg (in the formula, RI is a C, ~3 alkyl group, or a phenyl group) or RI-lithium (in the formula, RI is a C, ~3 alkyl group, or a phenyl group). Become. The reaction is carried out in an inert solvent at or below ambient temperature. Alkali metal borohydride (MBH4
, where M is an alkali metal, preferably lithium or sodium. ) to obtain carbinol of the formula melon, where RI is 1 and R is a lower alkyl group. halogenated RIMg,
Alternatively, by reaction with RI-lithium, a carbinol of the formula melon in which RI is a lower alkyl group or a phenyl group and R is a lower alkyl group is obtained. The prepared carbinol of formula X is then dehydrated to produce an alkenyl-substituted phenoxyalkanoic acid ester of formula X. This dehydration reaction converts carbinol of formula K into P-toluenesulfonic acid, P-toluenesulfonyl chloride, naphthalene-B in an inert solvent.
-sulfonic acid, metasulfonyl chloride-sulfur dioxide, chloromethyl sulfite, boron trifluoride ether key compound by heating with a dehydrating agent. This reaction is conveniently carried out at the reflux temperature of the solvent by taking measures to remove water produced in the reaction. The treatment of an olefinic acid ester of formula manufacture a certain compound.
Biological evaluation has shown that the compounds of this invention have cholesterol-lowering and triglyceride-lowering effects and are therefore useful for treating atherosclerotic symptoms caused by increased serum cholesterol and triglyceride levels. It has been shown that Both effects were measured by orally administering the compound of this invention to rats [Tumer et al., Soa elbow. J. Cljn. Buddha d. Invest Sasa atbn921
0 (1949): Armld et al., J. of A
ratioeroSC1eroSBResearch71
11-115 (1967)]. Male rats were fasted for 5 hours and dosed with the compounds of this invention through the gastric tube, then the rats were divided into two groups and 1
The flock is fed a normal diet, and the other sheep are fed a fat diet. Continue this diet for 5 days. Blood was collected by cardiac puncture on the fifth day. Serum samples are analyzed to determine the amount of cholesterol and triglycerides, and the values are recorded as the amount per 100 ml of serum. The effect of the compound of this invention is evaluated by the ED33 value, which is the dose that causes a decrease in serum cholesterol level or serum triglyceride level in 33% of the rats used. The compounds of this invention have a cholesterol-lowering effect of 15 to 15% in rats fed a normal diet.
It was found to have an ED33 value of 2-250 p/k9 regarding triglyceride lowering effect of 250 females/k9. In rats fed a fat diet, these ED33
The value was even lower. Data for individual compounds are as follows. Lipid-lowering activity (tested in rats for 5 days) *Commercial product: Ethyl 2-(p-chlorophenoxy)-2-methylpropionate The structure of the compounds of this invention was determined by synthesis, elemental analysis, infrared spectra and N. M. R. Determined by spectrum. The following examples are intended to illustrate, but not limit, the invention. Note that production examples using other methods are also described as reference examples.
Method A Reference Example 1 'a) p-Isoprobenylanisole P-toxyacetophenone (150 molar, 1.0 mol)
A solution of methyllithium (1.0 mol) in ether (1.66 mol) cooled in an ice bath was added dropwise to a solution of methyllithium (22 ml, 1.0 mol) in ether (1.66 mol). The reaction mixture was heated at 0° C. for 30 minutes, at room temperature for 30 minutes, and at reflux for 1 hour. To this refluxing mixture was added methyllithium twice in each corner for 30 minutes, 0.1 mole each. The resulting reaction mixture was added to an aqueous ammonium chloride solution, and the resulting aqueous layer was separated and extracted with ether. The extracted ether solutions were combined, washed with aqueous sodium bisulfite, dried over anhydrous sodium sulfate, and concentrated in vacuo. Distill the residue to P-
Isoprobenylanisole was obtained. bp75-81℃(
1.2 Yanagi) Yield 120.4% {b} p-(2,2-dichloro-1-methylcyclopropyl)anisole potassium tert-butoxide (228 mol, 2.04 mol) was kept at -40 qo. P-isoprobenylanisole (1
Chloroform (750 evenings) - Bentane (35 evenings)
The solution was added dropwise over 2.5 hours. The reaction mixture was heated at -40°C for 1 hour, then the cooling was removed and heating continued for 3 hours. The resulting reaction mixture was quenched in ice water, the layers were separated, and the aqueous layer was extracted with pentane. The pentane solutions were combined, washed with water, dried over anhydrous sodium sulfate, and concentrated in vacuo to give P as an oil.
Mono(2,2-dichloro-1-methylcyclopyl)anisole was obtained. Yield 190 evening {c) p-(2・2-
Dichloro-1-methylcyclopropyl)phenol boron tribromide (6.1 min, 0.0242 mol) in methylene dichloride (25 mol)

[) solution was cooled in an ice bath, P1(2
・2-dichloro-1-methylcyclopropyl)anisole (6.1 nights, 0.0264 mol) in methylene dichloride (
No. 25') was added dropwise to the concentrated Azusa solution. The reaction mixture was rinsed at 0° C. for 1 hour, then the ice was removed and the mixture was heated for an additional hour. The resulting reaction mixture was quenched with ice water and the layers were separated. Extract the aqueous layer with methylene dichloride, combine the methylene dichloride solution, wash with water,
It was then washed with dilute sodium hydroxide solution. At this point, P-(2,2-dichloro-1-methylcyclopropyl)
The sodium salt of phenol was isolated and collected by filtration.
The roasted mugwort was combined with the first water layer and made acidic with concentrated hydrochloric acid. The resulting acidic solution was extracted with ether, and the ethereal solution was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was recrystallized from carbon tetrachloride to obtain P-(2,2-dichloro-1-methylcyclopropyl)phenol. mp125~1
2 is ○ [d) 2-[P-(2,2-dichloro-1-methylcyclopropyl)phenoxy]-12-methylpropionic acid [in formula 1, A, A', and RI are CH3, R, R3
, R3', and Q are days, R2 and R2' are CI, and n is an integer 0] Chloroform (5.4
P-(2,2-dichloro-11-methylcyclopropyl)phenol (9.1 mm) and sodium hydroxide (7.2 mm) were dissolved in acetone (200 mm) by pressing the rope at the reflux point. and added dropwise to the mixture. After the addition was complete, the mixture was heated at reflux for 3 hours and then cooled in an ice bath. The resulting solid sodium salt was collected by filtration, washed with cold acetone, and dissolved in water. The resulting aqueous solution was acidified with concentrated hydrochloric acid, the resulting acidic mixture was extracted with ether, the ethereal solution was dried over anhydrous sodium sulfate, and concentrated in vacuo. The residual oil was crystallized by trituration with hexane and recrystallized from hexane to give 2-[P-(2,2-dichloro-1-methylcyclopropyl)phenoxy]-12-methylpropion as a pale cream solid. Obtained acid. mpl08~11r0 Yield: 8.5 pm In the above method, use equimolar amounts of iodoform or chlordiazomethane instead of chloroform, and each
-[P-(2,2-diiodo-1-methylcyclopropyl)phenoxy]-2-methylpropionic acid (A in formula 1)
, A', and RI are CH3, R, R3, R3', and Q are days, R2, and R2' are 1, and n is an integer 0.
P-positioning compound. ) or 2-[P-(2-chloro-1-methylcyclopropyl)phenoxy]-2-methylpropionic acid (formula 1
where A, A', and RI are CH3, R, R2', R3,
R3' and Q are days, R2 is CI, and n is an integer 0
P-positioning compound. ) was obtained. Reference Example 2 (a) Sodium P-(2,21-difluoro-1-methylcyclopropyl)anisolechlordifluoroacetate (
It was dried in vacuum at 5,000 °C on the evening of 91.5 before use. ) A warm solution of diglyme (175 birds) was added to the reflux solution of diglyme (500') of P-isoprobenylanisole (74 days) containing traces of trinitrobenzene and 4-tert-butylpyrocatechol as stabilizers. A total of 9 drops were added. The reaction mixture was stirred at reflux for 5 minutes, then cooled and filtered to obtain sodium chloride. Wash this sodium chloride with a little diglyme and then with pentane, mix the washings and furnace liquor with the water, and add 3 parts with bentane.
Extracted twice. The obtained pentane solution was mixed with 10% potassium hydroxide.
Aqueous solution, then washed with water, dried over anhydrous sodium sulfate, and concentrated in vacuo to give 96.5 kg of P-(2,2-difluoro-1-methylcyclopropyl)anisole as a straw-colored oil. [b- P-(2,2-difluoro-1-methylcyclopropyl)phenol was mixed with P-(2,2-difluoro-1-methylcyclopropyl)anisole at 9.9 p.m. by the method of {c' in Reference Example 1.
The same boron tribromide was dissolved in 200% ethylene dichloride to obtain a pinkish oil (90%) which solidified on standing. (c} 2-[P-(2,2-difluoro-1-methylcyclopropyl)phenoxy]-12-methylpropionic acid [in formula 1, A, A', and RI are CH
3, a P-positioning compound in which R, R3, R3', and Q are days, R2 and R2' are F, and n is an integer 0. ] by the method of {d} in Reference Example 1, P-( at 9.0 evening)
2,2-difluoro-1-methylcyclopropyl)phenol, 10.9% sodium hydroxide, and 8.1%
It was prepared by putting chloroform in 200ml of acetone. The product was recrystallized from hexane to give 2-[p-(2,2-difluoro-1-methylcyclopropyl)phenoxy]-2-methylpropionic acid as a pale cream solid at 8.5 min. Ta. mpllo~11rC Reference Example 3 {a) P-(2,2-dibromo-1-methylcyclopyl)anisole potassium t-poxide (Shiyu, 0.
75 mol) was cooled in a dry ice bath.
mol) of p-isoprobenylanisole and 480 mole(1
．． 9 mol) of promoform in 1350 ml of pentane was added dropwise to the mixture over 2 hours. The first 9G kettle was dropped at -40℃, and the next 30 minutes were at -10℃.
It was dropped at midnight. The resulting reaction mixture was concentrated at -10 qo for 1 hour, then the cooling rack was removed and the concentration continued for 3 hours. The mixture was quenched in ice water, the layers were separated, and the organic layer was washed with water, dried over anhydrous sodium sulfate, and concentrated in vacuo to give 99.5 mg of P-(2,2-dibromo) as a reddish-brown oil. monomethylcyclopropyl)anisole was obtained.
'b-p-(2,2-dibromo-1-methylcyclopropyl)phenol by the method of 'c) of Reference Example 1,
Prepared from 10 ml of p-(2,2-dibrom-1-methylcyclopropyl)anisole, 7.5 ml of boron tribromide, and 100 ml of methylene dichloride. 6 ml of p-(2,2-dibromo-1-methylcyclopropyl)phenol was obtained as an off-white solid.
[c'2-[p-2,2-dibromo-1-methylcyclopropyl)phenoxy]12-methylpropionic acid (in formula 1, A, A', and RI are CH3, R, R3, R3'
and Q is day, R2 and R2' are Br, and n is an integer 0
A P-positioning compound. ), by the method of {d} of Reference Example 1, P on 11.7 evening
-(2,2-dibromo-1-methylcyclopropyl)phenol, 15.2 hours of sodium hydroxide, 11.3 hours of chloroform, and 250 minutes of acetone. Recrystallized from ether-hexane as a pale cream-colored solid at 10.2 min.
-Methylpropionic acid was obtained. mp130-131.5
Reference Example 4 (a' p-(2,2-dichloro-3,3-dimethylcyclopropyl)anisole was converted into p-(2,2-dimethyl vinyl) anisole, 102 potassium t-phthoxide, 180
of chloroform, and 1800' of pentane. The product was recrystallized from hexane as colorless needles of P-
(2,2-dichloro-3,3-dimethylcyclopropyl)anisole was obtained. mp54.5-570{b) p-(2,2-dichloro-3,3-dimethyl.cyclopropyl)phenol was converted to 6 by the method of {c- in Reference Example 1.
It was prepared from 5.8 hours of P-(2,2-dichloro-3,3-dimethylcyclopropyl)anisole and 37.5 hours of boron tribromide. Recrystallization from a benzene-hexane solution yielded 23.5 ml of p-(2,2-dichloro-3,3-dimethylcyclopropyl)phenol. mplll~1
11.5℃ (c} 2-[p-(2,2-dichlor-3
13-dimethylcyclopropyl)phenoxy]12-methylpropionic acid (A, A', R3, and R3 in formula 1)
P-positioning compound where ' is CH3, R, R1, and Q are days, R2 and R2' are CI, and n is an integer 0. ) on the evening of 30.3 using the method of 'd) in Reference Example 1.
-(2,2-dichloro-3,3-dimethylcyclopropyl)phenol, 31.2 Sodium hydroxide, 23
．． Prepared from 2 hours of chloroform and 1000 minutes of acetone. The product was obtained as an oil. Reference Example 5 {a) P-(2,2-difluoro-3,3-dimethylcyclopropyl)anisole was converted to P-(2,2-dimethylvinyl) at 19.66 days by the method of {a- in Reference Example 2. It was prepared by adding anisole and 100% sodium chlordifluoroacetate to 700M diglyme. The product was distilled at 81-8〆○ (0.1 Yanagi) to 72.0
P-(2,2-difluoro-3,3-dimethylcyclopropyl)anisole was obtained. {bi P-(2・2
-difluoro-3,3-dimethylcyclopropyl)phenol was mixed with P-(2,2-difluoro-3,3-dimethylcyclopropyl)anisole for 31.8 days and P-(2,2-difluoro-3,3-dimethylcyclopropyl)anisole for 25 days by the method 'c-' of Reference Example 1. It was produced from boron tribromide. The product was used as it was in the next reaction without purification. (c) 2-[P-(2,2-difluoro-3,3-dimethylcyclopropyl)phenoxy]12-methylpropionic acid (in formula 1, A, A', R3, and R3' are CH
3, a P-positioning compound in which R, R1, and Q are days, R2, and R2' are F, and n is an integer 0; ), by the method 'd} of Reference Example 1, P of 3.96 evening
-(2,2-difluoro-3,3-dimethylcyclopropyl)phenol, 4.80 ml of sodium hydroxide, 3
．． It was manufactured from Madarayu's chloroform and 150 pieces of acetone. The product was obtained as an oil. Reference example 6 [a) p-(1,2-dimethylvinyl)anisole 15
A mixture of 0 ml of 2-(P-methoxyphenyl)-12-butanol and 360 m' of acetic anhydride was heated at reflux for 2.5 hours. The solvent was distilled off and the residue was fractionated. 11400 (10
From the last fraction obtained above, P-(1.
2-dimethylvinyl)anisole (mainly cis isomer) was obtained. (b) p-(2,2-dichloro-1,3-dimethylcyclopyl)anisole by method 'b' of Reference Example 1.
Prepared from 64.6 hours of P-(1,2-dimethylvinyl)anisole, 101 hours of potassium t-butoxide, 258 hours of chloroform, and 1800 hours of pentane. The product was distilled at 90-90 (0.07-0.0 molar) and P-(2.2-zik.ru 1.3) of 79.1 tem.
-dimethylcyclopropyl)anisole (80% cis isomer) was obtained. 'clp-(2,2-dichloro-1,
3-dimethylcyclopropyl)phenol, Reference Example 1
By the method of 'c', 79.1 days of p-(2,2-dichloro-1,3-dimethylcyclopropyl)anisole '46.9 days of boron tribromide, and 520 days' of dichloride. The product was recrystallized from a benzene-hexane solution to give 43.7 min of P-(2,2-dichloro-1) as colorless needles.
-3-dimethylcyclopropyl)phenol (cis isomer) was obtained. mp79-820 (d} 21 [p-(2
・2-dichloro-1,3-dimethylcyclopropyl)phenoxy]-2-methylpropionic acid (A, A' in formula 1)
, R1, and R3 are CH3, R, R3', and Q are days, R2 and R2' are CI, and n is the integer 0. ) was prepared by the method 'd} of Reference Example 1, P-(2,2-dichloro-1,3-dimethylcyclopropyl)phenol for 39.1 hours, sodium hydroxide for 40.6 hours, and 30.6 hours for sodium hydroxide.
Prepared from 2 hours of chloroform and 1275 hours of acetone. The product precipitated as a sodium salt (mp
200-20200) to form a free acid, recrystallized from an aqueous ethanol solution to obtain 21 [p-(2
・2-dichloro-1,3-dimethylcyclopropylene)
Phenoxy]-2-methylpropionic acid (methyl at the 1st position and methyl at the 3rd position are in cis position) was obtained. mp13
3.5-134-50○ Reference Example 7 {a} 0-(2,2-dichlorocyclopropyl)anisole was converted into 0-vinylanisole for 40.2 days by the method of {b) of Reference Example 1. , 84 μm of potassium t-topoxide, and 214 μm of chloroform were prepared in 1500 μm of pentane. Distill the product at 80-8500 (0.1 skin) to 7.9
0-(2.2-dichloropropyl)anisole was obtained for 4 hours. (b'0-(2,2-dichlorocyclopropyl)
Phenol was produced by the method of {c) in Reference Example 1 from 01(2,2-dichlorocyclopyl)anisole for 7.8 hours and boron tribromide for 5.3 hours. 7.1 hours of the oil obtained was used as such in the next reaction. {c'2-[0-(2,2-dichlorocyclopropyl)phenoxy]ethyl-2-methylpropionate (Formula 1
So A and A' are CH3, R is C2 day 5, R1, R3, R3
', and an ortho-positioning compound where Q is day, R2 and R2' are CI, and n is an integer 0. ) to 6.6 by the method (a} of Example 2, which will be described later).
0-(2,2-dichlorocyclopropyl)phenol, 12.7% Q-ethyl fromisobutyrate, and 1
3.5 ml of anhydrous potassium carbonate was added to 30 ml of dimethylformamide. The product was heated to ~100°C (0.
4.05) as a very pale yellow oil.
78 2-[0-(2,2-dichlorocyclopropyl)phenoxy]-12-methylp. Ethyl pionate was obtained. Reference Example 8 'a) P-(2,2-difluorocyclopropyl)anisole was prepared by the method of 'a-' in Reference Example 2, and 129 days of P-pynylanisole and 170 days of sodium chlordifluoroacetate were mixed with 1500 times of P-(2,2-difluorocyclopropyl)anisole. It was manufactured in a diglyme. P-(2,2-difluorocyclopropyl)anisole was obtained as a yellow oil. [b) P1 (2・2
-difluorocyclopropyl)phenol, Reference Example 1
Produced by the method of [c) from 120 ml of p-(2,2-difluorocyclopropyl)anisole and 81 ml of boron tribromide, and the obtained oily product 72 ml was used as it is in the next reaction. did. [c) 2-[P-(2,2-difluorocyclopropyl)phenoxy]-2-methylpropionic acid (A in formula 1)
and A' are C ratios, R, R1, R3, R3', and Q are 1
1. A P-positioning compound in which R2 and R2' are F, and n is an integer 0. ), P- at 25.5 evenings by the method of {d' in Reference Example 1
(2,2-difluorocyclopropyl)phenol, 3
Prepared from 6.0 ml of sodium mercury, 26.8 ml of chloroform, and 1100 ml of acetone. The product was recrystallized from a benzene-hexane mixture to give 2-[P-2.2-difluorocyclopropyl)phenoxy]-2-methylpropionic acid as cream-colored needles. mp97-99q0 Reference Example 9 (a-p-(2,2-dichlorocyclopropylmethyl)anisole 81.5 days p-(2-probenyl)anisole and 80.9 days p-(2-probenyl)anisole (C6 A mixture of 5HgCC12Br) in 200' of benzene was heated at reflux for 5.5 hours.The product was isolated and distilled to remove residual starting material and 120'
Chromatographed on 0.0 mL silica gel, eluting with bentane and then 1-4% ether in pentane. 28 hours of p-(2,2-dichlorocyclopropylmethyl)anisole was obtained as a yellow oil. (b-p
Mono(2,2-dichlorocyclopropylmethyl)phenol was added to p(2,2-dichloropropylmethyl)phenol for 28 days by the method of {c' in Reference Example 1.
・2-dichlorocyclopropylmethyl)anisole and 2
It was prepared from 0.0 ml of boron tribromide. The product was recrystallized from a benzene-cyclohexane mixture to give 17.3 hours of p-(2,2-dichlorocyclopropylmethyl)phenol as a beige solid. mp
57-6〆0{c'2-[p-(2,2-dichloropropylmethyl)phenoxy]-2-methylpropionate ethyl (Formula 1, A and A' are CH3, R is C2, R1 ,
A P-positioning compound in which R3, R3', and Q are days, R2 and R2' are CI, and n is an integer 1. ) will be described later in reference example 2.
It was prepared from 17.8 hours of p-(2,2-dichlorocyclopropylmethyl)phenol, 56 hours of ethyl Q-bromiisobutyrate, and 51.3 hours of potassium carbonate according to the method of {a--. 21 of 20.6 evening as a yellow oily substance [
Ethyl p-(2,2-dichlorocyclopropylmethyl)phenoxy-12-methylpropionate was obtained. 'd-2-[p-(2,2-dichlorocyclopropylmethyl)phenoxy]12-methylpropionic acid (in formula 1, A and A' are CH3, R, R1, R3, R3', and Q is p-positional compound where R2 and A2' are CI and n is an integer 1.) Ethyl 2-[p-(2,2-dichlorocyclopropylmethyl)phenoxy]-2-methylpropionate, 25 A mixture of 10% aqueous sodium hydroxide solution and 25% ethanol was heated at room temperature for 3 hours. The resulting reaction mixture was acidified and the resulting product was collected and recrystallized twice from hexane. and 10.0 evening 21 [
p-(2,2-dichlorocyclopropylmethyl)phenoxy]-2-methylpropionic acid was obtained. mp78~8
000 Reference Example 10 [a} 1,1-dichloro-2,3-dihydro-5-methoxyIH-cyclobropa[a]naphthalene (compound in which RI and R3' are days, R2 and R2' are CI, and the lower alkyl group is C&) ), 6-methoxy-3,4-dihydronaphthalene of 48 days, potassium t-butoxide of 84 days, and 227 days of
It was prepared by adding chloroform and 1,350 ml of pentane. 76 hours of product was obtained as a reddish-brown oil. [b)1・
1-dichloro-2,3-dihydro-IH-cyclopropa[a]-5-naphthol was converted to 1,1-dichloro-2,3-dihydro-5-methoxyIH-cyclopropyl on the evening of 24.4 by the method 'c-' of Reference Example 1. [a] Manufactured from naphthalene and 25.0 g of boron tribromide. The obtained reddish-brown oil of 21.4 hours was used as it was in the next reaction. 'c) 2-(1,1-dichloro-2,3-dihydroIH-cyclopropa[a]-5naphthyloxy)-2-propionic acid (in formula 1, A and A' are CH3, R,
R1 and R3' are days, R2 and R2' are CI, Q and R
3 together form a CH2C ratio, and n is an integer 0), according to [d} of Reference Example 1, 21.
1,1-dichloro-2,3-dihydro-IH-cyclopropa[a]-5-naphthol at 49, sodium hydroxide at 22.4, chloroform at 16.1, and 35
0' of acetone. Recrystallization from cyclohexane gave 2-(1,1-dichloro-2,3-dihydroIH-cyclopropa[a]-5-naphthyloxy)-2-propionic acid as an olive-gray powder. mpl04-106.60 Example 1 (
a} 2-(p-propionylphenoxy)-2-methylpropionic acid was converted into 3 by the method of [d-] of Reference Example 1.
It was prepared from 74 g of p-hydroxypropionphenone, 60 g of sodium hydroxide, 39 g of chloroform, and 7 g of acetone. 321 ml of 2-(p-propionylphenoxy)-2-methylpropionic acid was obtained. (bl 2-(p-propionylphenoxy)-2-methylpropionate 118 hours of 2-(p-propionylphenoxy)-2-methylpropionic acid, 48 hours of methanol, 3.5 hours of concentration) A mixture of sulfuric acid and 150 parts of ethylene dichloride was heated at reflux for 2 hours. The reaction mixture was cooled, the layers were separated, and the organic layer was washed with water, sodium bicarbonate solution, and water. , dried over anhydrous sodium sulfate, and concentrated in vacuo.
Distilled at 70 (0.08 ribs) to 21 (p) of 114.5 evenings.
-propionylphenoxy)-2-methylpropionate was obtained. mp47-490C{c} 2-[p-(1-hydroxypropyl)phenoxy]--2-methylpropionate methyl sodium borohydride (10.
0.279 mol) was kept at 5°C in an ice bath for 6 nights, 11
4.5 mol (0.4 mol) of methyl 2-(p-propionylphenoxy)-2-methylpropionate was added to a solution obtained by dissolving 500 ml of methanol. After the exothermic reaction slowed down, the ice rack was removed and the reaction mixture was allowed to stand at room temperature for 1 hour. The solvent was removed in vacuo and the residue was partitioned between ether and water containing slightly more acetic acid than needed to acidify the resulting aqueous layer. The ether layer was separated, washed with sodium bicarbonate solution, dried over anhydrous sodium sulfate, and concentrated in vacuo. 113 days of methyl 2-[p-(1-hydroxypropyl)phenoxy]-12-methylpropionate was obtained as a pale straw-colored oil. {d-2-[p-(1-probenyl)phenoxy]
-Methyl 2-methylpropionate 113 hours of 2-[p-(1-hydroxypropyl)phenoxy]-2-methylpropionate and 1.5 hours of p-thrynesulfonic acid were added to 1000' of toluene. The solution obtained by dissolving
Heated at reflux for 1 hour under a moisture trap. The reaction mixture was cooled, washed with aqueous sodium bicarbonate, dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was distilled at 95 to 10,000 (0.05 to 0.08 degrees) to obtain methyl 21[p-(1-probenyl)phenoxy]-2-methylpropionate of 33 days. n valley =
1.5281[e] 2-[p-(2,2-dichloro-
3-methylcyclopropyl)phenoxy]methyl-2-methylpropionate (A, A', R, and R8 in formula 1)
are CH3, R1, R3', and Q are days, R2 and R2'
is CI and n is an integer 0) by the method of {b} of Reference Example 1 to methyl 2-[p-(1-probenyl)phenoxy]-12-methylbropionate for 37.5 days. , 45 parts of potassium t-phthoxide, and 120 parts of chloroform in 750 parts of pentane. The product was chromatographed twice on a silica gel (2k9) column and the column was eluted with a mixture of pentane-ether (3:1) to remove 2-[p-(2,2-dichloro-3- Methylcyclopropyl)phenoxy]-2-methylpropionate was obtained. h valley=1-5252 Example 2 'a' 2-(4-acetyl-2-chlorophenoxy)
-204 ethyl 2-methylpropionate (1.2 mol) of 3-chloro-4-hydroxyacetophenone, 49
A solution consisting of 7 mols (3.6 moles) of potassium carbonate and 1140 mols of dimethylformamide was heated at 80 ml under a sieve. Then ethyl 2-from-2-methylpropionate (
230 minutes) was added over 5 minutes and the reaction mixture was heated for 1 hour. Add ethyl 2-bromo-2-methylpropionate for 230 minutes, stir for 1 hour, add ethyl 2-bromo-2-methylpropionate for 1 hour, and finally add ethyl 2-bromo-2-methylpropionate. I worshiped the insect time. After filtration, the filtrate was washed with ether, and the ether washings and dimethylformamide solution were combined and concentrated in vacuo. Partition the residue between a dilute solution of sodium chloride and ether, and add the ether solution to a 10% solution of sodium hydroxide and 10% sodium chloride.
% solution, dried over anhydrous sodium sulfate, and concentrated in vacuo. The retentate was distilled at 146q0 (above 0.02) and 176.
5 evening 21 (4-acetyl-2-chlorophenoxy)-
Ethyl 2-methylpropionate was obtained. (b} 2-(
Ethyl (4-acetyl-2-chlorophenoxy)-2-methylpropionate, 15'
A mixture containing 35% aqueous sodium hydroxide, 25% 95% ethanol, and 100% water was stirred for 15 minutes. The mixture was then acidified with hydrochloric acid, cooled, and the resulting solid product was collected and recrystallized from aqueous ethanol.
．． 35 minutes of 2-(4-acetyl-2-chlorophenoxy)-2-methylpropionic acid was obtained. mp123-12
500(c} 2-[4-(1-hydroxyethyl)-
Ethyl 2-chlorophenoxy]-2-methylpropionate was added to ethyl 2-chlorophenoxy]-2-methylpropionate by the method [c} of Example 1.
Prepared from ethyl (4-acetyl-2-chlorophenoxy)-2-methylpropionate and 1.9 hours of sodium borohydride. 30.0 evening -2-[4-(1-hydroxyethyl)-
Ethyl 2-chlorophenoxy]-2-methylpropionate was obtained. (d) 2-(4-pinyl-2-chlorophenoxy)-
Ethyl 2-methylpropionate was converted to 2-[4-(1-hydroxyethyl)-2-chlorophenoxy]-2-methylpropionic acid by the method of {d} in Example 1 at 28.6 days. 15 ethyl and trace amounts of p-toluenesulfonic acid
Produced in 0.0' toluene. The product was distilled from 110 to 114 q○ (0.05 square meters) to yield 12.96 ml of ethyl 2-(4-vinyl-2-chlorophenoxy)-2-methylpropionate. (e}
Ethyl 2-[2-chloro-4-(212-dichlorocyclopropyl)phenoxy]-2-methylpropionate (in formula 1, A and A' are CH3, R is C25, R1, R3
, and R3' is day, Q is 2-CI, and R2 and R2' are C
I, and a P-positioning compound in which n is an integer 0) was prepared using ethyl 2-(4-vinyl-2-chlorophenoxy)-12-methylpropionate for 26.8 days and ethyl 2-methylpropionate for 28 days by the method of {b- in Reference Example 1. of potassium t-butoxide, and 50 of [
It was prepared by putting 500 ml of chloroform into 500 ml of pentane. The product was distilled from 135 to 1370 (0. female side) and 19
．． Shoyu's ethyl 2-[2-chloro-4-(2,2-dichlorocyclopropyl)phenoxy]-12-methylpropionate was obtained. 'f) 2-[2-chlor-4-(2.2
-dichlorocyclopropyl)phenoxy]-2-methylpropionate (Formula 1, A and A' are CH3, R is C
2 days 5, R1, R3, and R3' are days, Q is 21 CI
, R2 and R2' are CI, and n is an integer 0) was converted into 2-(4-vinyl-2-chlorophenoxy)-2-methylpropion by the method of [b) of Reference Example 1] on 26.8 pm. It was prepared by placing ethyl acid, 28 g of potassium t-butoxide, and 50 g of chloroform in 500 g of pentane. The product was distilled at 135-13700 (0.08 side) to obtain ethyl 2-[2-chloro-4-(2,2-dichlorocyclopropyl)phenoxy]-12-methylpropionate on 19.22 pm. . Example 3 Ethyl 2-[2-chloro-4-(2,2-difluorocyclopropyl)phenoxy]-2-methylpropionate (in formula 1, A and A' are CH3, R is C2, R1, R3
, and R3' is day, Q is 2-CI, and R2 and R2' are F
, and a P-positioning compound where n is an integer 0) in Reference Example 2
It was produced by the method of (a) by adding ethyl 21(4-vinyl-2-chlorophenoxy)-12-methylpropionate of 40.3 days and sodium chlorodifluoroacetate of 32.9 days to 190M diglyme. The product was distilled over 112 to 114 q○ (0.01 ribs) to yield ethyl 2-[2-chloro-4-(212-difluorocyclopropyl)phenoxy]-2-methylpropionate of 26.39 mL. Example 4 [a] 2-(3-acetylphe/xy)-2-methylp. Ethyl pionate was added to 17
7-m-Hyderoxyacetophenone, 632-2-
Prepared from ethyl from-2-methylpropionate, 537 g of anhydrous potassium carbonate, and 1200 g of dimethylformamide. The product is 121-128.5 CO
(0.04 hours) to obtain ethyl 2-(3-acetylphenoxy)-2-methylpropionate of 227.3 hours. [b) Ethyl 2-[3-(1-hydroxyethyl)phenoxy]-2-methylpropionate in Example 1
By the method of 'c-', ethyl 2-(3-acetylphenoxy)-12-methylpropionate and 9.4
Prepared from sodium borohydride of 500 ml. 125.6 hours of ethyl 2-[3-(1-hydroxyethyl)phenoxy]-12-methylpropionate was obtained as an oil. {c) Ethyl 2-(3-vinylphenoxy)-2-methylpropionate by the method 'd} of Example 1,
It was prepared by adding 125.6 minutes of ethyl 2-[3-(1-hydroxyethyl)phenoxy]-12-methylpropionate and 4.5 hours of p-toluenesulfonic acid to 1500 degrees of toluene. 115.9 hours of ethyl 2-(3-vinylphenoxy)-2-methylpropionate was obtained as an oil. {d)2
-[m-(2,2-dichlorocyclopropyl)phenoxy]-2-methylpropionic acid (in formula 1, A and A' are CH
3, R, R1, R3, R3', and Q are days, R2 and R
2' is CI and n is an integer 0) by the method of [b} of Reference Example 1, 21 (
Prepared from ethyl 3-vinylphenoxy)-2-methylpropionate, 42.0 kg of potassium t-butoxide, 10.7 kg of chloroform, and 750 kg of pentane. Distill the product at 123-12500 (0.08 skin),
It was chromatographed on a ShiIJ Kagel (500 column) column. The column was eluted with pentane and a pentane-ether mixture, and the resulting purified ethyl 2-[m-(2,2-dichlorocyclopropyl)phenoxy]-2-methylpropionate was dissolved in 100% 95% ethanol. It was hydrolyzed with 35% sodium hydroxide solution for 1 hour. After 2 minutes at room temperature, the reaction mixture was diluted and made acidic, and the acidic solution was extracted with ether. The resulting ether solution was concentrated in vacuo, and the residue was crystallized from hexane at 8.77 p.m.
1[m-(2,2-dichlorocyclopropyl)phenoxy]-2-methylpropionic acid was obtained. mp84-86
00 Example 5 (a'2-(p-acetylphenoxy)-2-methylpropionic acid was converted to 545 by the method [d} of Reference Example 1).
It was prepared by placing 960 g of p-hydroxyacetophenone, 960 g of sodium hydroxide, and 715 g of chloroform in 11 g of acetone. The product was recrystallized from carbon tetrachloride and then isopropyl acetate to give 2-(p-acetylphenoxy)-12-methylpropionic acid as a pale cream solid. mpl
08-110qo'b} Ethyl 2-[p-(1-hydroxyethyl)phenoxy]-2-methylpropionate was purified by the method of 'c} of Example 1 at 141 o'clock 21 (
Prepared from p-acetylphenoxy)-12-methylpropionic acid and 10.7 grams of sodium borohydride. 140 ml of ethyl 2-[p-(1-hydroxyethyl)phenoxy]-2-methylpropionate was obtained as a pale yellow liquid. {c) Ethyl 2-(p-vinylphenoxy)-2-methylpropionate 116 2-[4-(
A mixture of ethyl 1-hydroxyethyl)phenoxy-2-methylbropionate and 92 molar p-toluenesulfonyl chloride in a 500-ship pyridine was heated at the reflux point to
The mixture was heated for 1 hour, maintained at room temperature for about 1 hour, and then heated again at reflux for 6 hours. The reaction mixture was poured into ice water and extracted with hexane. The resulting hexane solution was washed successively with dilute sulfuric acid, 10% potassium bicarbonate, water, and then saturated sodium chloride solution;
It was then dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was distilled at 104 to 11 ro (0.03 to 0.08 side) to obtain ethyl 2-(p-vinylphenoxy)-2-methylpropionate of 60 min. (d) 21 [p1 (
Ethyl 2,2-dipromecyclopropyl)phenoxy]-2-methylpropionate was converted to 21(p-vinylphenoxy)- on 23.4 evening by the method of {b} of Reference Example 1.
It was prepared from ethyl 2-methylpropionate, 39.2 hours of potassium t-poxide, and 1 hour of bromoform. The product was isolated and hydrolyzed but not further purified. 'e} Ethyl 2-[p-(2,2-dibromocyclopropyl)phenoxy]-2-methylpropionate was hydrolyzed with sodium hydroxide in aqueous ethanol at room temperature for 5 hours. The acid moiety was isolated and recrystallized from aqueous ethanol and then benzene-hexane to give 2-[p-(2.2
-dibromocyclopropyl)phenoxy]-2-methylpropionic acid (in formula 1, A and A' are CH3, R, R1, R
3, R3', and Q are days, R2 and R2' are Br, and n is an integer 0. A p-positioning compound was obtained. mp129~1
3ro Example 6 (a} 2-[p-(2-chloro-2-fluorocyclopropyl)phenoxy]ethyl 2-methylpropionate 13.6% 2-(4-vinylphenoxy)-2-methyl A mixture of ethyl propionate and 33% phenyldichlorofluoromethylmercury (C6 ratio M or CI2F) in 120% benzene was refluxed for 4 hours. The reaction mixture was left at room temperature for 2 hours. The remaining solution was mixed with pentane, filtered in an oven, and concentrated in vacuo to give 2-[p-(2-chloro-2-fluorocyclopropyl)] as an orange oil. Phenoxy]-2-
Ethyl methylpropionate was obtained, which was hydrolyzed as follows. {b) 2-[p-(2-chloro-2-fluorocyclopropyl)phenoxy]-2-methylpropionic acid (in formula 1, A and A' are CH3, R, R1, R3, R3
', and Q is day, R2 is CI, R2' is F, and n
is an integer 0), and its ethyl ester, ethyl 2-[p-(2-chloro-2-fluorocyclopropyl)phenoxy]-2-methylpropionate, is hydrated in an aqueous solution of sodium hydroxide in ethanol. Manufactured by disassembly. 2-[p-(2-chloro-2
-fluorocyclopropyl)phenoxy]-2-methylpropionic acid was obtained. mp97-1020 Example 7 {a) 2-(p-phenylacetylphenoxy)-2-
Ethyl methylpropionate was converted into p-phenylacetylphenol,
Prepared from 230 mg of ethyl 2-methylpropionate and 228 mg of potassium carbonate. Obtained the objective of 70 evenings. mplll0-113qo(b) 2-ethyl [p-(1-hydroxy-2-phenethyl)phenoxy]-2-methylpropionate with 101 ethyl 2-(p-phenylacetylphenoxy)-2-methylpropionate and 11
．． It was prepared from sodium borohydride of 4 ml to give 97.8 ml as a yellow oil. {c) 2-[D-(2-phenylvinyl)phenoxy]
Ethyl -2-methylpropionate was mixed with ethyl 2-[p-(1-hydroxy-2-phenethyl)phenoxy]-2-methylpropionate for 94.5 evenings and ethyl 2-methylpropionate for 1.3 evenings according to the method 'd' of Example 1. was prepared by adding p-toluenesulfonic acid to toluene. The product was recrystallized from 95% ethanol to obtain 53.5% of the desired product. mp55-6500 [d) 2-[p-(
2,2-dichloro-3-phenylsic. 25% of ethyl 2-methylpropionate and 39% of phenyldichlorofluoromethylmercury were added to 100% of benzene. The resulting mixture was heated under gentle reflux for 3 hours. Add 5 phenyldichlorofluoromethylmercury, 3
Heated at reflux for more than an hour. The resulting reaction mixture was heated at room temperature for 2
The mixture was kept for a day, then filtered, and the furnace liquid was evaporated in vacuo. The residue was poured into haxane, filtered, and concentrated in vacuo to give ethyl 2-[p-(212-diq.3-phenylcyclopropyl)phenoxy]-2-methylpropionate at 34.2 pm. Obtained as an oil. This oil was hydrolyzed but not purified. [e} 2-[p-(2,2-dichloro-3-phenylcyclopropyl)phenoxy]-2-methylpropionic acid (in formula 1, A and A' are CH3, R
, R1, R3', and Q are days, R3 is C6 days 5, R2
, R2′ is CI, and n is an integer 0), ethyl 2-[p-(2,2-dichloro-3-phenylcyclopropyl)phenoxy]-2-methylpropionate is dissolved in sodium hydroxide. It was produced by hydrolysis with an aqueous ethanol solution. The product was chromatographed twice on a silica gel column, eluting with benzane-ether (1:1), and the product was recrystallized from hexane-benzene (2:1) for 15 min.
1-[p-(2,2-dichloro-3-phenylcyclopropyl)phenoxy]-2-methylpropionic acid was obtained.
mp129-13 Example 8 (a) 2-(p-acetylphenoxy)-2-methylpropionate, 2-(p-acetylphenoxy)-2-methylpropionic acid [ Example 5, [a
'] with 96 methanol and 7' concentrated sulfuric acid.
It was produced by esterification by heating in chloroform of 0.00'. The product was isolated and distilled at 11400 (0.06 side) to yield the desired product at 206.6 mm. mp62~6yo{b
} 2-[p-(1,2-dimethylvinyl)phenoxy]-2-methylpropionate methyl sodium hydride (
On the evening of 15.1, 0.36 mol of 57% dispersion in oil was placed in a 2-k flask, and the oil was removed by rinsing three times with benzane. Anhydrous dimethyl sulfoxide (Z of 240) was added and the flask was capped and filled with nitrogen. The mixture was heated to 75-800C for 48 minutes and then cooled in an ice bath. 133.2 A solution of ethyltriphenylphosphonium bromide in 720 m of dimethyl sulfoxide is then added, the resulting mixture is stirred for 15 minutes, and then 7 m
The mixture was treated with a solution of 0.8 mol (0.30 mol) of methyl 2-(p-acetylphenoxy)-12-methylpropionate dissolved in 120 ml of dimethyl sulfoxide. The resulting reaction mixture was heated at room temperature for 3 hours and then poured into water. The organic layer was separated, washed with water and a saturated solution of sodium chloride, dried over anhydrous sodium sulfate, and dissolved as an oil (mixture of geometric isomers) at 81.8 min.
-Methyl 2-dimethylvinyl)phenoxy]-2-methylpropionate was obtained. (c} 21(p1(2・2−
Dichloro-1,3-dimethylcyclop. phenoxy]1-2-methylpropionic acid (A, A', R1 in formula 1)
, and R3 is CH3, R, R3', and Q is day, R
2 and R2' are CI, and n is an integer 0, a P-positioning compound)
By the method of 'b) of Reference Example 1, on 24.8 evening 21 [
Methyl p-(1,2-dimethylpinyl)phenoxy-2-methylpropionate, 28% potassium t-butoxide, and 50% potassium t-butoxide. Produced by adding roform to 500 volumes of pentane. The produced methyl ester was hydrolyzed with a 95% methanol solution of sodium hydroxide in a conventional manner. The obtained acid portion was recrystallized from a benzene-hexane mixture to obtain the desired product (mixture of geometric isomers) in 12.5 days. mpl38-14530 Example 9 2-[p-(2,2-dibromo-1,3-dimethylcyclopropyl)phenoxy]-2-methylpropionic acid (
In formula 1, A, A', R1, and R3 are C, R, R3'
, and a P-positioning compound in which Q is skin, R2 and R2' are Br, and n is an integer 0) was prepared by the method of [b} of Reference Example 1 to 21 [p-(1. 2-dimethylvinyl)phenoxy]methyl-2-methylpropionate, 3
5 ml of potassium t-ptoxide and 152 ml of bromoform were prepared in 500 ml of pentane. The produced methyl ester was hydrolyzed with a 95% ethanol solution of sodium hydroxide in a conventional manner, and the acid product was isolated and recrystallized from a benzene-hexane mixture to give the desired product as a light brown rosette crystal on 12.9 pm. I got it. mp141
~142.5°C (decomposition) Example 10'a) Ethyl 2-(p-benzoylphenoxy)-12-methylpropionate was converted to 198% p-hydroxybenzophenone by the method of Example 2. , 490 ml of 2-methylpropionate, and 485 ml of potassium carbonate. The neutral portion was isolated, and the resulting beige solid of 208% was recrystallized from a benzene-hexane mixture to give 21% of 180% (
Ethyl p-benzoylphenoxy)-2-methylpropionate was obtained. mp82-85q0'b} 21 [p-
Ethyl (1-phenylvinyl)phenoxy]-2-methylpropionate was prepared by the method of Example 8 'b-.
1.2 ethyl (p-benzoylphenoxy)-12-methylpropionate, 42.8 evening methyltriphenylphosphonium bromide, and 5.05 evening sodium hydride in dimethyl sulfoxide. It was manufactured by putting it in. 31.6 hours of ethyl 2-[p-(1-phenylpinyl)phenoxy]-2-methylpropionate was obtained as a yellow liquid. [c) 2-[p-(2,2-dichloro-1-phenylcyclopropyl)phenoxy]-2-methylpropionic acid (in formula 1, A and A' are CH3, RI is C5, R
, R3, R3', and Q are days, R2 and R2' are CI,
and P-positioning compound where n is an integer 0), 'b' of Reference Example 1
It was prepared from ethyl 2-[p-(1-phenylvinyl)phenoxy]-12-methylpropionate of 31.6 days, potassium tert-butoxide of 28 days, and chloroform of 50 atoms. The produced ethyl ester was hydrolyzed with sodium hydroxide in 95% ethanol by a conventional method, the acid product was isolated, and recrystallized from a benzene-hexane mixture to obtain the desired product as colorless needles. Ta. mp171~173oo
Example 112-[p-(2,2-dibromo-1-phenylcyclopropyl)phenoxy]12-methylpropionic acid (in formula 1, A and A' are CH3, RI is C6 ratio, R,
A p-positioning compound in which R3, R3', and Q are days, R2 and R2' are Br, and n is an integer 0) is converted into (
By the method of b-, ethyl 2-[p-(1-phenylvinyl)phenoxy]-12-methylpropionate [Example 10, 'b0, 35 min of potassium t-butoxide, and 152 min of potassium t-butoxide] Manufactured from bromoform. The resulting ethyl ester was hydrolyzed with sodium hydroxide in 95% ethanol in a conventional manner and the resulting acid product was isolated and recrystallized several times from a benzene-hexane slurry to give colorless needles as colorless needles. I got my purpose for 5 nights. mp176~
17800 (Gas generation) Example 12 2-[p-(2,2-difluoro-1-phenylcyclopropyl)phenoxy]-2-methylpropionic acid (in formula 1, A and A' are CH3, RI is C6 5, R, R3, R
3', and Q are days, R2 and R2' are F, and n is an integer 0. ) Ethyl phenoxy]-2-methylpropionate [Example 10, t
b}] and 80 hours of sodium chlordifluoroacetate in diglyme. The produced ethyl ester was hydrolyzed with sodium hydroxide in 95% ethanol by a conventional method, and the produced acid product was recrystallized from a benzene-hexane solution to obtain the desired product. mp97-99ko0 Example 13'a
- 2-[p-(1-methylpinyl)phenoxy]-2
-Methyl methylpropionate was prepared by the method of Example 8 [b-] for 52.5 days.
b}], 107 days of methyltriphenylphosphonium bromide, and 12.6 days of sodium hydride were placed in dimethyl sulfoxide. Distill the product at 93-95oC (0.1 kite) 37.
I got my objective for the 5th night. {b} 2-[p-(2,2-dichloro-1-ethylcyclopropyl)phenoxy]-2
- Methyl propionate (P-positioning compound in formula 1 where A, A', and R are CH3, RI is C2, R3, R3', and Q are day, R2 and R2' are CI, and n is an integer 0) ), using method 'b- of Reference Example 1, on 18.5 evening 2
It was prepared from methyl 1[p-(1-ethylvinyl)phenoxy]-2-methylpropionate, 21 hours of potassium t-butoxide, and 56 hours of chloroform and was obtained as a pale straw-colored oil. bp 131-13300 (0.0 km) Yield 18.5 ta By the above method, 3-methyl-4-hydroxyacetophenone was reacted with ethyl 2-from-2-methylpropionate in the presence of potassium carbonate to produce 2-(2 -methyl-4
-acetylphenoxy)-2-methylpropionate was formed. This was treated with methyltriphenylphosphonium bromide in the presence of sodium hydride to give 2-[2-
Methyl-4-(1-methylvinyl)phenoxy]-2-
Ethyl methylpropionate is produced and this product is
In the presence of Jum t-butoxide. 〇 Ethyl 2-[2-methyl-4-(2,2-dichloro-1-methylcyclopropyl)phenoxy]-2-methylpropionate (formula 1, where A, A', R1, and Q are CH
3, R is C2, 5, R3 and R3' are days, R2 and R2' are CI, and n is an integer 0) Reference example 11 'a-p-(2,2-di) A solution obtained by dissolving 0.248 mol of p-(2,2-dichlorocyclopropyl)aniline in 185 volumes of glacial acetic acid was cooled to about 10 q0, and the fly colony solution was A solution of sodium nitrite (18.9 mm, 0.273 mol) in water (185 mm) was added dropwise to the solution. The formed high-strength slurry was added little by little to a solution of concentrated sulfuric acid (160 ml) in water (320 m') maintained at 100-105 qo. The resulting reaction mixture was heated at 10°C for 10 minutes, then cooled and diluted with water. The resulting product was collected by filtration, dissolved in ether and washed with sodium bicarbonate. The resulting ethereal solution was then extracted with sodium hydroxide solution, which was made acidic and extracted with ether. The obtained ether solution was dried and concentrated in vacuo, and the residue (18 yen) was steam distilled to give 9
A yellow gum-like substance was obtained. This crystallized when triturated with ether. I got my objective on the 8th. mp54.5-5600 (b-2-[p-(2,2-dichlorocyclopropyl)phenoxy]-2-methylpropionic acid (in formula 1, A and A' are CH3, R, R1, R3
, R3' and Q are days, R2 and R2' are CI, and n
(0.0356 mol) of p-(2,2-dichlorocyclopropyl)phenol,
A mixture of 11.2 kg (0.28 mol) of sodium hydroxide, 11 kg of chloroform, and 350 kg of acetone was prepared at 0°C. The cooling rack was removed and the mixture was allowed to stand for 1 minute, then heated on a steam bath to reflux temperature. The resulting reaction mixture was concentrated at reflux for 3 hours and then concentrated in vacuo. Partition the residual gum between dilute hydrochloric acid and ether, separate the ether layer, dry and
Concentrated in vacuo. The residual oil (14 min.) was partitioned between dilute sodium bicarbonate solution and ether. The resulting sodium bicarbonate solution was acidified with concentrated hydrochloric acid and extracted with ether. The resulting solution was dried over anhydrous sodium sulfate and concentrated. The residue (9.5 min., yellow oil) was crystallized twice from hexane to give the desired product as a pale cream solid at 6.0 min. mpl14-11600 reference example 12
Ethyl 2-[p-(2,2-dichlorocyclopropyl)phenoxy]-2-methylpropionate (A, A in formula 1)
', and R is CH3, R1, R3, R3', and Q
is a p-positioning compound where R2 and R2' are CI and n is an integer 0).
2-dichlorocyclopropyl)phenoxy)-12-methylpropionic acid [Reference Example 11, 'b}], 3.33 pm (
A mixture of 0.1038 mol) methanol and 0.5 mol concentrated sulfuric acid in 100 ml methylene dichloride was heated at reflux for 4 hours. The resulting reaction mixture was cooled, washed with water and sodium bicarbonate solution, dried, and concentrated in vacuo. The residue was distilled.
The desired product was obtained as a colorless oil after 8.5 hours. bplly
C (〇, 05 side) By another method, ethyl 2-[p-(2,2-dichlorocyclopropyl)phenoxy]-12-methylpropionate was added to p-(2,2-dichlorocyclopropyl) for 20 days. Propyl) phenol [Reference Example 11, 'a)], 2-from-2-methylpropionate ethyl chloride, and 42 ml potassium carbonate were mixed in 100 ml of acetonitrile. The starting material, ethyl 2-from-2-methylpropionate, was added in two equal parts and a second time was added after heating at reflux for 7 hours. The resulting reaction mixture was heated at reflux for about 3 days, and the product was isolated and converted to 2-[p-(2.2-
Ethyl dichlorocyclopropyl)phenoxy-12-methylpropionate was obtained. This was hydrolyzed in a conventional manner with an ethanol solution of sodium hydroxide to give 2-[p-(2.2
-dichlorocyclopropyl)phenoxy]-2-methylpropionic acid was obtained. In the above alternative method, instead of ethyl 2-from-2-methylpropionate, an equimolar amount of 2
- methyl 2-(n-propyl)acetate, methyl 2-from-2-ethylbutyrate, methyl 2-from-2-methylbutyrate, or methyl 2-from-2,3-dimethylbutyrate, respectively. [p-(2,2-dichlorocyclopropyl)phenoxy]-2-(n-propyl) ethyl cyanate (in formula 1, A and A' are C ratio CH2CH3,
p-positioning compound where R is CH3, R1, R2, R3, and Q is day, R2 and R2' are CI, and n is an integer 0, 2-
[p-(2,2-dichlorocyclopropyl)phenoxy]-methyl 2-ethylbutyrate (in formula 1, A and A' are C2&,
R is CH3, R1, R3, R is and Q is day, R2 and R
2' is CI and n is an integer 0, p-positional compound), 2-[p-(2,2-dichlorocyclopropyl)phenoxy]-2-methylbutyrate (formula 1, A and R are C ratio, A ′
is C2 day 5, R1, R3, R3', and Q is day, R2
and R2′ is CI, and n is an integer 0);
or 2-[p-(2■2-dichlorocyclopropyl)
phenoxy]-2,3-dimethylate (A in formula 1)
and R is CH3, A' is CH(CH3)2, R1, R3
, R3', and Q are days, R2 and R2' are CI, and n is an integer 0.

Claims (1)

[Claims] 1 Formula I: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R is H, or an alkyl group of C_1_ to_6; A
and A' are respectively C_1_-_3 alkyl groups; Q is H
, a halogen atom, or an alkyl group of _1_ to _3; R
^1 is H, an alkyl group of C_1_-_3, or a phenyl group; R^2 and R^2' are each H or a halogen atom, and at least one is a halogen atom; R^3
is H, an alkyl group of C_1_-_3, or a phenyl group; R^3' is H, or an alkyl group of C_1_-_3;
Formula X: ▲Mathematical formulas, chemical formulas, tables, etc.▼ 3
' is as defined above. ) is treated with a medium that generates a carbene of the formula: :CR^2R^2' (wherein R^2 and R^2' are as defined above); optionally, R
is an alkyl group, it is hydrolyzed to produce an acid in which R is H; and, if desired, this acid is converted into its basic salt.