JPH0570631B2 - - Google Patents

Description

[Detailed description of the invention]

a Industrial Application Field The present invention is an intermediate useful in the manufacture of pharmaceutical products.
The present invention relates to (S)-hydroxy-5-methylnon-1-enes and a method for producing the same. More specifically, the present invention relates to 3(S)-hydroxy-5(S), which is an optically active compound useful as a synthetic intermediate for prostaglandins.
Or, it relates to (R)-methylnon-1-enes and their production method. b Prior art 3(S)-hydroxy-1-iodo-5(S)-methylnon-1-ene and 3(S)-hydroxy-
1-Iodo-5(R)-methylnon-1-ene is described in JP-A-58-32834. Tokukai Akira
According to Publication No. 58-32834, the compound is optically active binaphthol as shown in Flowsheet-1.

Using an asymmetric reducing agent obtained from [Chemical formula], 5-methyl-1
-iodo-non-1-en-3-one. On the other hand, it is also possible to obtain the compound by resolution from the dl form, for example, JHFried (J.Am.Chem
According to the method of -Soc., 94, 7827 (1972) et al., the salt of alcohol hemiphthalate and (-)-α-methylbenzylamine is separated by fractional recrystallization, but the yield is low. Low (10-15%). The above 3(S)-hydroxy-5-methylnon-1-enes contain two asymmetric carbon atoms, and as far as the inventors know, there is no known method for splitting such chain alcohols. It hasn't been done yet. Furthermore, JP-A-54-130556 describes an optical resolution method using compounds represented by the following formulas 1 and 2, and Pestic.Sci, 11, 188 (1980)
The following formulas 1, 2, 3,
4, an optical resolution method using
Chem. Ber. 115, 1591 (1982) describes an optical resolution method using a compound of formula 5 below as a resolution method for CRNoe.

【formula】 【formula】

【formula】

【formula】

[Formula] The above-mentioned literature describes optical resolution methods for several types of alcohols using these compounds, but there is no mention of the aforementioned 3-hydroxy-5-methylnon-1-enes. do not have. c. Purpose of the Invention The present inventors paid attention to the above-mentioned points and determined that 3(S)-hydroxy-5(S) or (R)-
As a result of intensive research on methods for obtaining methylnon-1-enes, the present invention was achieved by discovering that a novel splitting method can achieve this objective. Therefore, an object of the present invention is to provide 3(S)-hydroxy-5(S)- or 5(R)-methylnon-1-enes useful as synthetic intermediates for prostaglandins. d Structure and effects of the invention According to the present invention, the following formula [I]

[Formula, X represents a halogen atom, Y represents an oxygen atom or two hydrogen atoms, and A represents a carbon number of 3 to 15]
represents a hydrocarbon having 3-membered rings or bicyclo[2,2,1] rings. It is further provided that the hydrocarbon chain A contains one or more chiral atoms or that the ether component is otherwise capable of exhibiting chirality due to the asymmetric configuration of the entire molecule. ] 3-hydroxy-5-methyl nona-
3(S), 5(S) form, 3(S), 5 of 1-enes
(R) body, 3(R), 5(S) body, 3(R), 5(R)
3-hydroxy-5-methylnon-1-enes, or any mixture thereof. Among these, considering that it is used as an intermediate for prostaglandins, 3(S),
5(S), 3(S), and 5(R) forms are preferred. X represents a halogen atom, and examples thereof include fluorine, chlorine, bromine, and iodine, with iodine being preferred, especially considering its use as an intermediate for synthesizing prostaglandins. In addition, in the above formula [I], the following formula containing A

[Formula] [Here, A and Y are the same as defined above]
is preferably (1R,4R,5S)-6,6-dimethyl-2-oxo-3-oxabicyclo[3,1,
0] Hex-4-yloxy group, (1S, 4S, 5R)
-6,6-dimethyl-2-oxo-3-oxabicyclo[3,1,0]hex-4-yloxy group, (3R,3aR,4S,7R,7aR)-1-oxo-
3a,4,7,7a-tetrahydro-4,7-methano-(3H)-isobenzofuran-3-yloxy group, (3S,3aS,4R,7S,7aR)-1-oxo-
3a,4,7,7a-tetrahydro-4,7-methano-(3H)-isobenzofuran-3-yloxy group, [2S-(2α,3aα,4α,7α,7aα)]-2,3
，
3a,4,5,6,7,7a-octahydro-7,
Examples include 8,8-trimethyl-4,7-methanobenzofuran-2-yloxy group. Therefore, the 3-hydroxy-5-methylnon-1-enes of the present invention have the following formula []

[In the formula, X is the same as defined above. ] 3-hydroxy-5-methyl nona-
1-enes and the following formula []

[In the formula, A and Y are the same as defined above,
R represents a hydrogen atom or a lower alkyl group, or

[Formula] [wherein A and Y are the same as defined above. ] and form a dimer. ] It is produced by reacting a compound represented by the following in the presence of an acid or by a dehydration method. 3-Hydroxy-5-methylnon-1-ene, which is the raw material compound used here, is produced by the method shown in Flow Sheet 2 below, as also described in JP-A-58-32834. Ru. Flow sheet 2

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[Formula] This raw material compound can be separated into two by having asymmetric carbon atoms at the 3rd and 5th positions. That is, 3(S), 5(R) body, 3(R), 5
(S) mixture and 3(R), 5(R), 3
It may be separated into a mixture of (S) and 5(S) bodies, and this separated mixture may be used for reaction. Acids used to react these compounds include acidic compounds such as hydrochloric acid, sulfuric acid, hypochlorous acid, strongly acidic ion exchange resins, para-toluenesulfonic acid, methanesulfonic acid, camphorsulfonic acid, and boron trifluoride. or its pyridine salt, among which p-toluenesulfonic acid and its pyridine salt are particularly preferred. As the dehydration method, an azeotropic gradient method or a dehydrating agent is used. Examples of the dehydrating agent include magnesium sulfate,
Preferred examples include molecular sieves and activated anhydrous calcium sulfate, but are not limited to these. The amount of acid used is 0.01 to 1 equivalent, particularly preferably 0.1 to 0.3 equivalent, relative to 3-hydroxy-5-methylnon-1-ene. In addition, the amount of the resolving agent represented by the above formula [] is based on 3-hydroxy-5-methylnon-1-enes.
The amount is from 0.3 equivalents to 3 equivalents, particularly preferably from 0.6 equivalents to 1.3 equivalents. As a solvent for the reaction, common organic solvents such as ether, tetrahydrofuran, acetone, chloroform, dichloromethane, dichloroethane, benzene, toluene, xylene, petroleum ether, and hexane are used. Particularly when using an azeotropic gradient method, benzene and toluene are preferred. The reaction temperature is from 0°C to 150°C, preferably from room temperature to 90°C. The reaction time varies depending on the catalyst used and reaction temperature, but is usually 5 minutes to 120 minutes.
time, preferably from 2 hours to 10 hours. Thus, 3-hydroxy-5 of the above formula [I]
-Methylnon-1-enes are obtained. After the completion of the reaction, to obtain the target compound, a diastereomer derived from the asymmetric carbon atom to which the hydroxyl group at the 5-position of the 3-hydroxy-5-methylnon-1-ene skeleton is bonded, that is, a diastereomer of the following formula [I -a]

[In the formula, X, A, and Y are the same as defined above. ] and the following formula [I-b]

It is possible to separate the compounds represented by: Specifically, silica gel chromatography, alumina chromatography, dry chromatography, liquid chromatography, thin layer chromatography, etc. are preferably used as such a separation method. By such a separation method, the compound represented by the above formula [I-a] and the compound represented by the above formula [I-b], which can be derived from natural prostaglandins, can be easily obtained. However, the above formula [I-
The compound represented by a] is reacted in the presence of a neutral or acidic agent, water or alcohol, and separated and purified as necessary to form the following formula [']

[In the formula, X is a halogen atom, 〓 represents an asymmetric center, and represents the R form, the S form, or any mixture thereof. ] Optically active 3(S)-hydroxy-5 represented by
-Methylnon-1-enes are obtained. The reaction can be carried out in a neutral state, but an acidic agent may also be used. Preferred examples of the acid agent include acidic compounds such as hydrochloric acid, sulfuric acid, hypochlorous acid, para-toluenesulfonic acid, camphorsulfonic acid, and their pyridine salts, with para-toluenesulfonic acid and its pyridine salts being particularly preferred. The reaction is carried out in the presence of water or alcohol, and the alcohol is preferably methanol or ethanol. The solvent for the reaction is preferably water-soluble, such as dioxane, tetrahydrofuran, acetone, methanol, ethanol, ethylene glycol, DMSO.
etc. can be mentioned preferably. Although X is a halogen atom, iodine is preferable, especially considering its use as an intermediate for synthesizing prostaglandins. The reaction temperature is from 0°C to 150°C, preferably from room temperature to 90°C. The reaction time varies depending on whether it is neutral or the acid agent used and the reaction temperature, but is usually 5 minutes to 120 hours.
Preferably it is from 2 hours to 10 hours. After the reaction, it is isolated and purified by column chromatography after normal post-treatment, but when the raw material compound used is one of the above formula [] in which the asymmetric carbon at the 5-position is optically active, 3(S)-hydroxy-5(S)- or -5(R)-methylnona-1-
Enes are obtained, but when the asymmetric carbon at the 5-position is not optically active as a raw material compound, 3(S)-hydroxy-5-methylnona-1- is obtained after the reaction.
Since enes are obtained, it is necessary to separate the stereoisomer at the 5-position. For such separation, column chromatography, ie, silica gel chromatography, alumina column chromatography, dry column chromatography, liquid chromatography, thin layer chromatography, etc., is usually preferably used. Such separation leads to 3(S)-hydroxy-1- which can lead to natural prostaglandins.
iodo-5(S)-methylnon-1-ene and 3
(S)-Hydroxy-1-iodo-5(R)-methylnon-1-ene is obtained. As shown in Flow Sheet-3 below, the water and oxygen of such a compound are protected by a silyl group, and then used for the reaction. Flow sheet-3

[ka]

[ka]

[ka]

[ka]

[ka]

[Chemical formula] Thus, the 3(S)-hydroxy-5 of the present invention
(S) or (R)-methylnon-1-enes can be converted into optically active prostaglandins. The above-mentioned prostaglandins are useful as pharmaceuticals that act on smooth muscle, blood pressure, lipid metabolism, platelet aggregation, etc. Therefore, 3(S)-hydroxy-5(S) or ( R)-Methylnon-1-enes are useful compounds. Hereinafter, the present invention will be explained in more detail with reference to Examples. Reference example 1

[Chemical formula] 1-iodo-5-methylnon-1-ene-3-
Dissolve 8.4 g (30 mmol) of sodium borohydride in 30 ml of ethanol and add 570 mg of sodium borohydride at 0°C.
(15 mmol) was added to a 10 ml ethanol solution. 45
After stirring for several minutes, the solvent was distilled off, saturated ammonium chloride water was added, extraction was performed with ethyl acetate, and the mixture was dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure,
Column chromatography (silica gel, solvent;
Separation and purification was performed using n-hexane/ethyl acetate = 19/1) to obtain 3(S)-hydroxy-1-iodo-
5(R)-Methylnon-1-ene and 3(R)-hydroxy-1-iodo-5(S)-methylnon-1-
4 g (47%) and 3(S)-hydroxy-1-
iodo-5(S)-methylnon-1-ene and 3
3.8 g (45% ) was obtained. NMR (δppm in CDCl ₃ ) (same spectrum) 6.55 (1H, dd, J=14Hz, 5Hz), 6.2 (1H, d,
J=14Hz), 4.1 (1H, m), 1.2~1.6 (7H, m),
0.85 (3H.d, J=6Hz), 0.8 (3H, m) IR (cm ^-1 , neat) (same spectrum) 3350, 2950, 2900, 1610, 1460, 1380, 1170,
950 Example 1

[Chemical formula] 3(S)-hydroxy-1 obtained in Reference Example-1
-iodo-5(R)-methylnon-1-ene and 3
208 mg (0.74 mmol) of a mixture of (R)-hydroxy-1-iodo-5(S)-methylnon-1-ene and (1R,4R,5S)-6,6-dimethyl-4-hydroxy-3-oxabicyclo [3.1.0] Dissolve 115 mg (0.81 mmol) of hexan-2-one in 30 ml of benzene, add 40 mg (0.16 mmol) of PPTS (pyridinium para-toluenesulfonate), and heat the mixture to reflux. The reaction is allowed to proceed for 6 hours while removing the produced water using an azeotropic system. After the reaction, ethyl acetate is added, PPTS is removed by washing with water, and after drying, the solvent is distilled off.
Column chromatography (silica gel, solvent;
(S)- with benzene/ethyl acetate = 20/1)
3-[(1R,4R,5S)-6,6-dimethyl-2-
Oxo-3-oxabicyclo[3.1.0]hexan-4-yloxy]-1-iodo-5(R)-methylnon-1-ene (less polar; TLC (silica gel), Rf=0.58, solvent benzene/ethyl acetate =
10/1) 130 mg (43%) and (R)-3-[(1R,
4R,5S)-6,6-dimethyl-2-oxo-3-
Oxabicyclo[3.1.0]hexan-4-yloxy]-1-iodo-5(S)-methylnona-1-
En (more polar; TLC (silica gel), Rf=
0.50, solvent benzene/ethyl acetate = 10/1) 125
mg (42%).

[Formula] (less polar part); NMR (δppm in CDCl ₃ ) 0.7-1.0 (6H, m), 1.1 (6H, s), 1.0-1.8
(9H, m), 2.0 (2H, s), 4.2 (1H, m), 5.1
(1H, s), 6.4 (2H, m) IR (cm ^-1 , neat) 2950, 2900, 1780, 1600, 1460, 1380, 1350,
1280

[Formula] (more polar part); NMR (δppm in CDCl ₃ ) 0.7-1.0 (6H, m), 1.1 (6H, s), 1.0-1.8
(9H, m), 2.0 (2H, s), 4.15 (1H, m), 5.15
(1H, s) IR (cm ^-1 , neat) 2950, 2900, 1780, 1600, 1460, 1380, 1350,
1280 Example 2

[Chemical formula] 3(S)-hydroxy-1 obtained in Reference Example-1
-iodo-5(S)-methylnon-1-ene and 3
1 g (3.5 mmol) of a mixture of (R)-hydroxy-1-iodo-5(R)-methylnon-1-ene and (1R,4R,5S)-6,6-dimethyl-4-hydroxy-3-oxabicyclo [3.1.0]Hexane-
2-one 560 mg (3.9 mmol) and PPTS 200 mg
Example 1 from a 100ml benzene solution of (0.8mmol)
Similarly, (S)-3-[(1R, 4R, 5S)-6,
6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexan-4-yloxy]-1-iodo-5(S)-methylnon-1-ene (less
polar; TLC (silica gel), Rf=0.58, solvent benzene/ethyl acetate=10/1) 600 mg (42%) and (R)-3-[(1R,4R,5S)-6,6-dimethyl-2- Oxo-3-oxabicyclo [3.1.0]
hexane-4-yloxy]-1-iodo-5
(R)-Methylnon-1-ene (more polar;
TLC (silica gel), Rf=0.50, solvent benzene/
585 mg (41%) of ethyl acetate (10/1) was obtained.

[Formula] (less polar part); mp.56-58 ℃ NMR (δppm in CDCl ₃ ) 0.7-1.0 (6H, m), 1.1 (6H, s), 1.0-1.7
(9H, m), 2.0 (2H, s), 4.2 (1H, m), 5.15
(1H, s), 6.4 (2H, m) IR (cm ^-1 , KBr) 2950, 2900, 1770, 1600, 1460, 1400, 1380,
1350, 1280

[Formula] (more polar part); mp.51-56 ℃ NMR (δppm in CDCl ₃ ) 0.8-1.0 (6H, m), 1.1 (6H, s), 1.0-1.8
(9H, m), 2.0 (2H, s), 4.15 (1H, m), 5.2
(1H, s), 6.45 (2H, m) IR (cm ^-1 , KBr) 2950, 2900, 1765, 1610, 1460, 1400, 1380,
1340, 1280, 1240 Example 3

[Chemical formula] 3(S)-hydroxy-1 obtained in Reference Example-1
-iodo-5(R)-methylnon-1-ene and 3
A mixture of 2801 mg (1 mmol) of (R)-hydroxy-1-iodo-5(S)-methylnon-1-ene and (1S,4S,5R)-6,6-dimethyl-4-hydroxy-3-oxabicyclo[ 3.1.0] Hexan-2-one 156 mg (1.1 mmol) and PPTS 50 mg
(0.2 mmol) in 20 ml of benzene solution,
Similarly to 1, (S)-3-[(1S, 4S, 5R)-
6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexan-4-yloxy]-1-
iodo-5(R)-methylnon-1-ene (more
polar; TLC (silica gel) Rf = 0.50, solvent benzene/ethyl acetate = 10/1) 185 mg (45%) and (R)-3-[(1S,4S,5R)-6,6-dimethyl-2-oxo -3-Oxabicyclo [3.1.0]
hexane-4-yloxy]-1-iodo-5
(S)-Methylnon-1-ene (less polar; TLC
(Silica gel) Rf=0.58, solvent benzene/ethyl acetate=10/1) 173 mg (43%) was obtained.

[Formula] (less polar part); NMR (δppm in CDCl ₃ ) 0.7-1.0 (6H, m), 1.1 (6H, s), 1.0-1.8
(9H, m), 2.0 (2H, s), 4.15 (1H, m), 5.15
(1H, s), 6.4 (2H, m) IR (cm ^-1 , neat) 2950, 2900, 1780, 1600, 1460, 1380, 1350,
1280

[Formula] (less polar part); NMR (δppm in CDCl ₃ ) 0.7-1.0 (6H, m), 1.1 (6H, s), 1.0-1.8
(9H, m), 2.0 (2H, s), 4.2 (1H, m), 5.1
(1H, s), 6.4 (2H, m) IR (cm ^-1 , neat) 2950, 2900, 1780, 1600, 1460, 1380, 1350,
1280, Example 4

[ka]

[Chemical formula] 3(S)-hydroxy-1-iodo-5(R)-methylnon-1-ene and 3(R)-hydroxy-1
228 mg (0.8 mmol) of a mixture of -iodo-5(S)-methylnon-1-ene and [2R,2R'-(2α,
2′α, 3aα, 3a′α, 4α, 4′α, 7α, 7′α, 7aα,
7a′α)]-2,2′-oxybis(2,3,3a,4,
5,6,7,7a-octahydro7,8,8-trimethyl-4,7-methanobenzofuran (MBF
-O-MBF) 116 mg (0.31 mmol) in 10 ml
Dissolve in dry ether, add 1g of molecular sieve (4Å), and add 10mg of p-toluenesulfonic acid.
(0.06 mmol) and stirred at room temperature for 1 hour.
After the reaction, the solvent was distilled off and the O-MBF-
3(R)-Hydroxy-1-iodo-5(S)-methylnon-1-ene 121 mg (43%) (TLC; Rf=
0.6, solvent n-hexane/ether = 19/1 silica gel) and O-MBF-3(S)-hydroxy-1-iodo-5(R)-methylnon-1-ene93
mg (33%) (TLC; Rf = 0.5, solvent n-hexane/ether = 19/1 silica gel).

[Formula] (less polar part); NMR (δppm in CDCl ₃ ) 0.7-1.0 (6H, m), 0.85 (3H, s), 0.9 (3H,
s), 0.95 (3H, s), 1.0~1.9 (16H, m), 2.65~
3.2 (1H, m), 4.2 (2H, m), 5.3 (1H, s), 6.3
(2H, m) IR (cm ^-1 , neat) 2950, 2900, 1600, 1450, 1370, 1170, 1090,
1070, 1040, 990, 950

[Formula] (more polar part); NMR (δppm in CDCl ₃ ) 0.7-1.0 (6H, m), 0.85 (3H, s), 0.9 (3H,
s), 0.95 (3H, s), 1.0~1.9 (16H, m), 2.6~
3.1 (1H, m), 4.1 (2H, m), 4.2 (1H, m), 5.35
(1H, m), 6.25 (1H, dJ=15Hz), 6.6 (1H, dd,
J=15Hz, 5Hz) IR (cm ^-1 , neat) 2970, 2950, 2900, 1610, 1460, 1390, 1370,
1320, 1210, 1180, 1100, 1080, 1040, 1010,
1000,960 Example 5

3(S)-hydroxy-1-iodo-5(S)-methylnon-1-ene and 3(R)-hydroxy-1
-Iodo-5(R)-methylnon-1-ene mixture 157 mg (0.56 mmol) and MBF-O-MBF96
mg (0.26 mmol) in 10 ml dry ether,
Add 1 g of molecular sieve (4 Å), add 10 mg (0.06 mmol) of p-toluenesulfonic acid, and stir at room temperature for 1 hour. The solvent was distilled off, and the O-MBF-3(R)-hydroxy-
1-Iodo-5(R)-methylnon-1-ene 85 mg
(43%) (TLC; Rf = 0.6, solvent n-hexane/ether = 19/1 silica gel) and O-MBF-
3(S)-hydroxy-1-iodo-5(S)-methylnon-1-ene 67 mg (34%) (TLC; Rf=0.5,
A solvent (n-hexane/ether = 19/1 silica gel) was obtained.

[Formula] (less polar part); NMR (δppm in CDCl ₃ ) 0.7-1.0 (6H, m), 0.85 (3H, s), 0.9 (3H,
s), 0.95 (3H, s), 1.0~1.9 (16H, m), 2.65~
3.2 (1H, m), 4.2 (2H, m), 5.3 (1H, s), 6.3
(2H, m) IR (cm ^-1 , neat) 2970, 2950, 2900, 1600, 1490, 1450, 1390,
1370, 1310, 1270, 1260, 1210, 1180, 1110,
1090, 1070, 1030, 1010, 990, 950

[Formula] (more polar part); NMR (δppm in CDCl ₃ ) 0.7-1.0 (6H, m), 0.85 (3H, s), 0.9 (3H,
s), 0.95 (3H, s), 1.0~1.9 (16H, m), 2.65~
3.2 (1H, m), 4.0 (1H, m), 4.2 (2H, m), 5.35
(1H, s), 6.35 (2H, m) Example 6

[Chemical formula] (S)-3-[(1R, 4R,
5S)-6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexan-4-yloxy]
-1-Iodo-5(R)-methylnon-1-ene
Dissolve 120ml (0.3mmol) in 3ml of dioxane,
Add 3ml of water. p-toluenesulfonic acid 5
mg, heated to 80°C and stirred for 2 hours. After the reaction, the solvent was distilled off under reduced pressure, and the reaction mixture was dissolved in ethyl acetate and washed with saturated sodium hydrogen aqueous solution. By acidifying the aqueous layer with hydrochloric acid and extracting with ethyl acetate, (1R,4R,5S)-6,6-dimethyl-2
40 mg (95%) of -oxo-3-oxabicyclo[3.1.0]hexan-4-ol are recovered. The organic layer was further washed with saturated brine, dried, the solvent was distilled off under reduced pressure, and subjected to silica gel chromatography (solvent: n-hexane/ethyl acetate =
9/1) to obtain 76 mg (90%) of 3(S)-hydroxy-1-iodo-5(R)-methylnon-1-ene. [α] ^23/D −1.64° (C=0.4 MeOH) Example 7

[Chemical formula] (S)-3-[(1R, 4R,
5S)-6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]hexan-4-yloxy]
-1-Iodo-5(S)-methylnon-1-ene
250 ml (0.62 mmol) of 5 ml of dioxane and 5
Dissolve in ml of water and add 10mg of p-toluenesulfonic acid.
Add and heat to 80℃. After stirring for 2 hours, Example-
Similarly to 6, (1R,4R,5S)-6,6-dimethyl-2-oxo-3-oxabicyclo[3.1.0]
81 mg (92%) of hexane-4-ol was recovered and 3
160 mg (95%) of (S)-hydroxy-1-iodo-5(S)-methylnon-1-ene was obtained. [α] ²³ _D −8.95° (C=0.9 MeOH) Example 8

[Formula] O-MBF-3(S)-hydroxy-1-iodo-5(S)-methylnona-1 obtained in Example-5
Dissolve 65 mg (0.14 mmol) of -ene in 2 ml of methanol, add p-toluenesulfonic acid, and stir for 10 hours. After the reaction, ethyl acetate was added, and after washing with saturated sodium bicarbonate water, the solvent was distilled off and 3(S)-hydroxy-1-iodo -5(S)-methylnon-1-ene 36 mg (95%,
Rf=0.36) and O-MBF-methanol 25mg
(85%, Rf=0.9) was obtained. [α] ²² _D +8.9° (C=0.6 MeOH)

Claims (1)

[Claims] 1 The following formula [I] [Formula] [In the formula, X represents a halogen atom, Y represents an oxygen atom or two hydrogen atoms, and A has a carbon number of 3 to 15
represents a hydrocarbon having 3-membered rings or bicyclo[2,2,1] rings. It is further provided that the hydrocarbon chain A contains one or more chiral atoms or that the ether component is otherwise capable of exhibiting chirality due to the asymmetric configuration of the entire molecule. ] 3-hydroxy-5-methyl nona-
3(S), 5(S) form, 3(S), 5 of 1-enes
(R) body, 3(R), 5(S) body, 3(R), 5(R)
3-hydroxy-5-methylnon-1-enes, or any mixture thereof. 2. 3-hydroxy- according to claim 1, wherein in the above formula [I], X is an iodine atom
5-methylnon-1-enes. 3 In the above formula [I], the following formula [formula] containing A (where A and Y are the same as defined above)
is [Formula] (1R,4R,5S)-6,6-dimethyl-2-oxo-3-oxabicyclo[3,1,0]hex-4-yloxy group, [Formula] (1S,4S,5R) -6,6-dimethyl-2-oxo-3-oxabicyclo[3,1,0]hexa-
4-yloxy group, [Formula] [2S-(2α, 3aα, 4α, 7α, 7aα)]-2,3,
3a,4,5,6,7,7a-octahydro-7,
3-hydroxy- according to claim 1 or 2, which is any 8,8-trimethyl-4,7-methanobenzofuran-2-yloxy group.
5-methylnon-1-enes. 4 The following formula [] [Formula] [In the formula, X is a halogen atom. ] 3-hydroxy-5-methyl nona-
1-enes and the following formula [] [Formula] [In the formula, Y represents an oxygen atom or two hydrogen atoms, A represents a hydrocarbon having 3 to 15 carbon atoms, and a 3-membered ring or a bicyclo [ 2, 2, 1]
form a ring. It is further provided that the hydrocarbon chain A contains one or more chiral atoms or that the ether component is otherwise capable of exhibiting chirality due to the asymmetric configuration of the entire molecule. R represents a hydrogen atom or a lower alkyl group, or represents a group [formula] [wherein A and Y are the same as defined above] to form a dimer. ] The following formula [I] [Formula] [wherein X, A, and Y are the same as defined above] be. ] 3-hydroxy-5-methyl nona-
Method for producing 1-enes. 5 The following formula [] [Formula] [In the formula, X is the same as defined above. ], the stereochemical combination of carbons at the 3rd and 5th positions is a mixture of 3(S), 5(R) and 3(R), 5(S) or 3(S), 5(S). 5. A method for producing 3-hydroxy-5-methylnon-1-enes according to claim 4, which is carried out using a mixture of 3(R) and 5(R) forms. 6 The compound represented by formula [] is (1R, 4R,
5S)-6,6-dimethyl-4-hydroxy-3-
Oxabicyclo[3,1,0]hexan-2-one or (1S,4S,5R)-6,6-dimethyl-4
-Hydroxy-3-oxabicyclo[3,1,
0] hexane-2-one, or (3R, 3aR, 4S,
7R, 7aS)-3-hydroxy-3a,4,7,7a-
Tetrahydro-4,7-methano-(3H)-isobenzofuran-1-one, or (3S, 3aS, 4R,
7S,7aR)-3-hydroxy-3a,4,7,7a-
Tetrahydro-4,7-methano-(3H)-isobenzofuran-1-one, or [2S-(2α, 3aα,
4α, 7α, 7aα)] −2, 3, 3a, 4, 5, 6, 7,
7a-octahydro-7,8,8-trimethyl-
4,7-methanobenzofuran-2-ol, or [2R, 2′R-(2α, 2′α, 3aα, 3a′α, 4α, 7α,
7′α, 7aα, 7a′α)]-2,2′-oxybis(2,
3,3a,4,5,6,7,7a-octahydro-
7,8,8-trimethyl-4,7-methanobenzofuran) The method for producing 3-hydroxy-5-methylnon-1-enes according to any one of claims 4 to 5 . 7. Claims 4 to 6, wherein the acid is at least one selected from the group consisting of hydrochloric acid and sulfuric acid.
A method for producing 3-hydroxy-5-methylnon-1-enes according to any one of the above items. 8. Any one of claims 4 to 6, wherein the acid is at least one selected from the group consisting of paratoluenesulfonic acid, methanesulfonic acid, camphorsulfonic acid, and pyridine salts thereof. The method for producing the 3-hydroxy-5-methylnon-1-enes described above. 9. 3 according to any one of claims 4 to 6, wherein the dehydration method is carried out using an azeotropic tilt method.
-Production method of hydroxy-5-methylnon-1-enes. 10. The method according to any one of claims 4 to 6, wherein the dehydration method is carried out using at least one member selected from the group consisting of molecular sieves, activated anhydrous calcium sulfate, and anhydrous magnesium sulfate. Method for producing 3-hydroxy-5-methylnon-1-enes.