JPS61100577A - Production of aminofuranone - Google Patents

Abstract

PURPOSE:A readily available nitrile such as 2-acetoxy-2-methylpropanenitrile is used as a starting material and treated with a base to enable high-efficiency production of the titled compound which is used as a starting material for hypotensor or plant growth retarder. CONSTITUTION:A ketone is converted into a cyanohydrin, the product is acylated or a ketone is allowed to react with a cyanated trimethylsilyl in the presence of a catalyst to form a cyanohydrin trimethylsilyl ether. Then, the product is allowed to react with acetic anhydride in the presence of a catalyst to give a compound of formula I (R<1>, R<2> are alkyl, aryl, R<1> and R<2> incorporate to form alkylene or polymethylene; R<3> is H, halogen, alkyl, acyl, aryl, arylthio, arylsulfinyl). The product is treated with a base such as diisopropylamine or triethylamine to give an aminofuran of formula II such as 4-amino-5,5- dimethyl-2(5H)furanone.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention is based on the general formula (wherein 81 and kLz are alkyl M or an aryl group and 6p, and Ru 1 and Ru 2 together can form a Si, Purkyle 7 group, or a polymethylene group) 03 is a hydrogen atom, a halogen atom, a lower alkyl group, an acyl group, an aryl group,
It is an arylthio group or an arylsulfinyl group. ) relates to a method for producing aminofuranone.

By reacting the aminofuranone represented by the general formula σ) obtained by the present invention with incyanate,
It is known that this urinary cord spindle is useful as a medicine that has monohypertensive effect (see Japanese Patent Application Laid-open No. 139056/1982), and is also known to be useful as a drug with antihypertensive effect. *It is known to be useful as a growth retardant or a withering agent (see I! #Ensho 50-148352).

Conventionally, the method for producing aminofuranone represented by the above general formula (2) involves reacting a tetronic acid spinner with dorazine, followed by catalytic hydrogenation. Synthesis f: A method of reduction is known (see JP-A-52-139056); however, this method is difficult to synthesize tetronic acid.
6 cannot be produced in good yield and is difficult to put into practical use. The present inventors have conducted intensive studies on the method for producing amino 7-quinone, and as a result, have found an efficient method and have produced the BAt-producer of the present invention.

The present MA has the general formula (in the formula, R1 and R2 are an alkyl group or an aryl group, and R2 and R2 together can form an alkylene group or a polymethylene group. The aminofuranone gold represented by the above-mentioned general formula (2) is produced by treating a compound (such as an alkyl group, an acyl group, an aryl group, an arylthio group, or an arylsulfinyl group) with a base.

The compound represented by the general formula 〇 in this Q-mei is obtained by (1) converting the ketone into a cyanohydrin and then acylating it, or
(2) After reacting the ketone with trimethylsilyl cyanide in the presence of a catalyst to obtain cyanohydrin trimethylcryl ether (alphakvans et al., J
, (Jrg+Chew+3L 914(1984
)) by reacting acetic anhydride in the presence of a catalyst (kL G
anem at al, + J, Org, Cbe
m-* 39s3728 (see (1,974))) is a compound that can be easily produced.

As R3 of the compound represented by the above general formula (1), water gg
It can be tuffed with a tuff, a Hagen atom, a lower alkyl group, an acyl group, an aryl group, an arylthio group, or an arylsulfinyl group.

In addition, R1 and R8 are an alkyl group, an alkylene group, or Bm
Full medium or polymethylene i in which l and 82 are combined
I can list t. Specifically, specific compounds represented by the general formula (1) include 2-acetoxy-2-methylpropanenitrile, 2-acetoxy-2-methylbutanenitrile, 2-acetoxy-2,2-pentamethyleneacetonitrile, and 2-acetoxy-2-ethylbutanenitrile. , 2-7 setoxy 2-methyl nona 7 products tolyl, 2
-A7Toxy 2,3-dimethylbutane Tolyl, 2-
A7-toxy 2-diphenylatonitrile, 2-acetoxy-2-ethyl-3-methylbutane tolyle, 2
-acetoxy-2-methylundecanenitrile, 2-a7toxS/-2-methyl-3-phenylpropanenitrile, 2-acetoxy-2-benzyrubutane trile,
2-Tolyl in acetate, 2-Ethyl undecyl, 2-
Acetoxy 2-methyl nitrile, 2-acetoxy-2,3-methylpentanenitrile, 2-acetoxy-2,3,3-)limethylbutane trile, 2-acetoxy-2-methyl octabutanenitrile, 2-acetoxy -2-methyloctanenitrile, 2-acetoxy-2
-Cyclohexylpropane nitrile, 2-7 setoxy 2-methyl nona 7 products tolyle, 2-7 setoxy 2-phenylpropane product tolyle, 2-acetoxy-2-7 enylpta/nitrile, 2-acetoxy-2-[β-naphthyl]propane Nitrile, 2-acetoxy-2-(6-medoxy7-2-tphthyl)propanenitrile, 2-/thi-2-propionylox7propanenitrile, 2-pentamedelene-2-propionyloxyacetonitrile,
2-chloroacetoxy-2-methylpropanenitrile,
2-promoacetoxy7-2-methylpropane product tolyl,
2-/thi-2-phenylacetoxypropanenitrile, 2-/loloa-7toxy-2,2-pentamethyleneacetonitrile, 2-bromoacetoxy-2,2-pentamethyleneacetonitrile, 2-methyl-2-(phenylteoa7toxy) (in) propanenitrile, 2-methyl-2-(
7g Nilsulfinyl acetoxin furopanenitrile,
2-(acetoacetoxy)-2-methylgropanenitrile, 2-7-7-pentamethylene acetonitrile, 2-aceto-1,7-2,2-tetramethylene acetonitrile, etc. can be removed.

In the present invention, the compound represented by the general formula 〇 in is treated with a base. Examples of bases that can be used include alkali metal salts of @2-hydranamine such as diinoprobylamine and hexamethyldisilazane; Alkaline earth metal salts, tertiary amines such as triethylamine, diimpropylethylamine, diethylaniline, pyridine, λ6-lutidine, 4-dimethylaminopyridine, alkali metal or alkaline earth metal hydrides and t-butylene Alcolades such as 7caritum can be exemplified.

The present invention can be carried out using ether systems such as tetrahydrofuran, diethyl ether, metheral, dimethoxyethane, etc., which do not directly participate in the reflux 6.

Processing temperature! tri-sac ~ 80C range and progresses to a circular beak. When using sodium hydride, ritetamamide, etc. as a base, the desired reaction mixture can be treated with a neutralizing agent. You can turn things into silver. Examples of neutralizing agents that can be used include aqueous solutions of ammonium chloride, methylamine hydrochloride, pyridine Shiozaka salt, and carboxylates such as hexaacids and globionic acids. The neutralization temperature is Nf! from the temperature of the above cyclization reaction. It is an era name within the range of .

Furthermore, among the aminofluorones represented by the general formula (2) in stI, those in which Bs is an acetyl group can be synthesized in one step from the precursor, cyanohydrin, without isolating the starting materials used in the present invention. Oru (Example 17)
.

Hereinafter, a detailed explanation will be given based on Examples and Reference Examples.〇Reference Example 1 Acetone cyanohydrin 1.7 g (20 mmol)
Dissolve ft Jikzono Kuritan at 20 dVc, add acetic anhydride 4, Od (70 mmol), and PilJ gin 3. under water cooling with OW.
21 Lt (40 mmoj) was added and stirred for 2 days at Yuuon. The reaction mixture was washed 3 times with 20 au of 31 hydrochloric acid, washed once with saturated saline for 9 nights, and dried with dichloromene Nt baric anhydride magnez 9 mm. The solvent was then electrolytically removed under reduced pressure, and then 1.213 g (yield: 450%) of the desired 2-7cetoxy-2-methylpropanenitrile was obtained by distillation under reduced pressure.

bp-70~75G/9Tory-”H-NMR (CDCIs): 1j 1.76 (
$-6H) t2.09' (s, 31()・IR(neat): 2260,1?60,1470.
1420°1390.1370,1355,1275°123Ll+ 1190-1140--'.

MS: m/z (relative intensity) + t2B CM”+b
2L112 (4), 84 (7), 68 (5
6).

ti7 (23), 61 (23), 52 (11
).

44 (10) f 43 (100) t 42 (13)
, 41 (84), 39 (23).

27(11)・Reference Example 2 Isoglobil methyl ketone o, 8sg (10mmo
l) 'i-c line benzene 1 u, 0ILtf'c common understanding, 7 am conversion under water cooling, trimedel 7 k 1.5 aj (
11 mmol), add catalytic zinc iodide (40 yen) with O, let it naturally warm from ice temperature to rim temperature, stir for 2 hours, and add 30 yen of water to the 90 yen reaction solution. In addition, the mixture was extracted with benzene, dried over benzene mt-anhydrous gnesium, and the solvent was distilled off under reduced pressure. To the crude product t and 5.0% of acetic anhydride, anhydrous iron chloride (I [[) (408F)) as a catalyst was added under water cooling, and the mixture was stirred at the same temperature for 1 hour. Add 30 d of dichloromethane to the reaction solution and add 30 d of dichloromethane to the reaction solution.
-, the dichloromethane layer 1 was dried with anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure, and the desired 2-7 heptene-2,3-dimethylbutanenitrile o, 77 g (yield: 50 g) was obtained.

b9135-140C/26-29g.

”) l-NMK (CDCI, ): J 1.08
Oh! Hi1.13 (2d.

Each J = 5.4Hz 6) ri e 1.6 B
(s, 3M), 2.1)8 (s, 3)i),
2.08~mu16 (m, lH).

IR(neat): 3000,2250.1755.
1470°1370.1235cm-'.

jdl: m7g (relative intensity) e 156 (M
+-1,2).

113 (29), 112 (5n, 96(
12), 95 (28), 80 (8) #71 (
88), FuO (17), 69 (18).

6B (22) # 55 (12)-53 (13)-4
3 (100), 41 (46), 39 (21).

Example 3 0.85 g (5 mmol) of nonyl methyl ketone and 5.0 dKl of dry benzene were dissolved, 7 ko of trimethyl cyanide and 8 td (6 mmol) were added under water cooling, and then 11 L of catalyst powder was added (20 JIP). - Add 3 parts of water (14t7
1G, extract benzene and remove benzene layer from anhydrous 9! After drying over magnesium chloride, the solvent was removed under reduced pressure. 3. The treated crude product was mixed with acetic anhydride. Dichloromethane 30°C was added to the catalyst anhydrous iron chloride (ILL) (20 Misaki) under water cooling, and the reaction mixture was naturally heated to a storm temperature and stirred overnight.
Add ajt, add Chaos hydrogen carbonate) Wash with 30 d of lime water bath solution, dry with anhydrous magnesium acid, 1#*'kv
Then, 0.95 g (yield: 79%) of the desired 2-acetoxy-2-methylundecanenitrile was obtained by distillation under reduced pressure.

b9 88-90 CI 0.15 Torr.

"H-NMH-(CDCl2): do, 82-0.9
5 (m-3H).

1.28 (brs, 14)i)t L72 (it
3)i), 1.76~LO3(-2H), λ07(s
e 3'L)・IR(neat): 2925.2855.2230,
1750°1?10,1460e 1370e i230a++-'.

MS: m/z (relative intensity) #240 m”+
1s O, 6) 1197 C3) e 196 (5),
180 (2).

171 (3), i70 (3), 154 (3)
.

150 (6), 136 (8), 127 (2)
.

112 (5), 110 (5), 109 (11),
95 (18n, 86 (9), 83(
16) e 71 (13) + 69 (12) −
68 (12), 58 (14), 57 (13λ5
5 (19), 43 (100), 42 (9).

Reference Example 4 1.2 g (10 mmol) of acetophenone was mixed with 10.0 acJKgN of dry benzene, and diluted with 4.5 d (11 mmol) of trimethyl 7-phosphate under water cooling.
Zinc iodine (20 aF) was added to the mixture, the temperature was naturally raised from ice temperature to base temperature, and the mixture was stirred overnight. Add 30 dt of water to the reaction solution, perform a benzene layer, and remove the benzene layer with anhydrous g! The obtained crude product was dissolved in 5.0 μl of acetic anhydride, and under water cooling, anhydrous iron chloride (CIII) (100 q) was added as a catalyst. The water temperature was returned to trap temperature and stirred overnight. Add 301 Lt of dichloromethane and 301 Lj of cell 5FIJ sodium hydrogen suboxide water seedling solution to the reaction solution, perform an extraction operation, separate the dichloromethane layer, and dry the organic layer with anhydrous magnesium sulfate.
After that, the #1 solvent is distilled off under reduced pressure, and the mixture is transported to the desired destination.
2-7 Setoxy 2-phenylpropane product Tolyl 1.7
O bp 56-58C10,15 Torr was obtained (yield: 90 g).

"ti-NMR (C1) CI, ): δ2.00 (so
3H), 2.13(8,38), 7.33-7.
58 (rrb 5)1)-IR(neat): 30
75,3050,3010.2950°1?90.14
95.1445,1370°1220am-'.

MS: m/x (relative 9irK), 1s9
(M”, 1), 147 (74L 146 (14)
, 130 (43) p105 (18L 103 (
28), 77-(28), 51 (17), 43
(100)-Reference Example 5
mmol l)', benzene 7.5JltKN, under water cooling, trimethylsilyl cyanide Q, 74i! j (5
, 5 mmol) Next, 4 capes of zinc iodide were added, and the temperature was allowed to rise naturally from the ice temperature to the mold temperature, and the mixture was stirred for 3 hours. 20 d of benzene and 30 d of water were added to the reaction solution and an extraction operation was carried out, and benzene h111i was fractionated, KA was carried out with anhydrous magnesium sulfate, and the benzene was removed under reduced pressure. Add anhydrous vinegar to the resulting crude product! lil! 10.6 m, add anhydrous iron chloride (m) (20 ar) under water cooling, and
The mixture was stirred for 15 minutes at 90°C, cooled on ice, and dichloromethane was added at 30°C.
I got m with j. The dichloromethane layer was diluted with saturated brine, dried over magnesium, and evaporated under reduced pressure. The resulting crude I! Thin t-curicaglu thin layer chromatography developing solvent hexane-#Ethyl Saka 4:
l] and ff& to the desired 2-77toxy-2-(
6-Medicucina 7chirun-propane nitrile 0.82g
(yield 492%) t-obtained.

”267-68.5C (dec,).

'H-f'1R414 (CDC1m): δL
O? (s, 3)i), 2.14 (so 3M)
, 3.92 (s, 31), 7.11 (st
1 to 'L), 7.23 (s, 18),
7.42 and 7.52 (λd+ J = LB H!
+1)L), 7.71 (S, 1)1), 7.
80 (s.

1)i)? , 96 (d, J=1.5Hz, 1)
1)-IIL(KBr): 3120.3075.30
50.3020゜2950.2855.2250,17
55゜1630.16101 1510,1490゜1
470.1450.1393, 1380°1350*
1270- 1230 (sh) 1120sh 10g5
．． 1035.960°890.870.801 knee 1°MS: m/z (relative intensity), 270 (M
”+l#5).

2690, 29), 227 (25).

226 (9), 211 (18) l 210 (Zo
o), 167 (12), 166 (9).

43 (23).

Reference example 6 Penzyl methyl ketone 0.67 g (5 mmol
) @Dissolve 10.0 mK of dry Ben 9F and cool with water to dissolve trimethylsilyl cyanide 0.73 al (6 mmo I
), add Oite catalyst heron zinc iodide (20 capes),
Allow the temperature to rise naturally from the ice temperature to the mold temperature, add 20 ILtt of recovered water, remove the benzene, dry the benzene over anhydrous magnesium sulfate, and remove the bath under reduced pressure. The crude product '4IJ obtained by 5.
0 m, anhydrous iron chloride (Ill.
) (20q) Extract the dichloromethane 30aj and a saturated sodium bicarbonate water bath [30ILt] to the solution, which was heated to room temperature and stirred overnight. Reduce the pressure of the dry ice solvent with Gnesicum to ``1 mfL,! The concentrated product was fractionated by silica gel thin layer chromatography ('NK opening solvent: xane-ethyl acetate 10:1) to obtain the desired 2-benzylpropanetrile, 0.49 g (yield). AA 49
Whisper) 1- Got it.

bp 140-150C/1-1.5 Torr.

Rf value 0.15-0.24 (gi(J,, hexane-
Acetic acid fs,,10:1)・”H-NMkL (C1)C1,N;J
1.68 (s, 3M), 2.06 (S・3
Fin, 3.17 and 3,29 (ABquartet
e J=13.5Hz+2H)-7,32(brs,
5) i).

IR(neat) 2 3100. 3060. 2
970. 2275°1760,15001 1455
．． 1375°1265.123G, 1150.1070
゜1020on-'.

MS: m/z (relative method &:) + 204 (M++
1.2).

143 (49), 116 (13), 115 (11)
, 91 (7G), 77 (4), 65 (10), 43
(100)Φ Reference Example 7 Diethyl ketone 0.86 g (l Om+no 1
) f dry benzene 10. tliljKfllM and diluted with 77-trimethylsilicate/k 1.5aj (l
1 mmol), then the biliary rooster's yokuka sub-sample (20'
P) t-Added and stirred from ice temperature to -5 with base. 30 JIjt of water was added to the reaction solution, and benzene extraction was performed. The benzene was removed by drying with anhydrous magnesium, and the solvent was removed under reduced pressure. The obtained crude product was dissolved in anhydrous vinegar [4, Oaj, and anhydrous iron chloride (1 ([) (100
Misaki) was added, and the mixture was stirred for 3 hours in an ice-cold bowl. Add 301 liters of dichloromethane to the reaction solution and 30 d and t of saturated ash-based sodium hydroxide solution to extract F! :I operation, separate the chloromethane layer and dry it with anhydrous m*magne 7cum.
The solvent was removed under reduced pressure, and the residue was distilled under atmospheric pressure to obtain the desired 2-ethylbutanenitrile in 2-acetate.
96 g (61% yield) t-obtained 90 bp 95-96 CI 20 Torr.

"H-NMR (CDCI,): J 1.05
(t, J x6.9) 1g.

6H), 2.04 ((Le J =6.9)it
, 4H).

2.09 (so 3M)・-IR (neat): 3000+ 2950.2245
．． 1750°1460.1370.1230tan-1°M
S: m/z (relative method 1, 156 (M++
1*5).

126 (15) I 113 (9), 112 (11
), 96 (26), 95 (89).

94 (13), 87 (17), 80 (42)
.

69 (28), 68 (61), 67 (67)
.

61 (19), 57 (63), 55 (20).

54 (12), 53 (2B), 52 (10)
.

44 (24) B 43 (100), 42 (17) I
41 (4)) s 39 (34).

Reference Example 8 Cyclohexanonecyanocytophosphorine L88g (15mm
o 1) in dichloromethane 20J17, and anhydrous vinegar m 3. Od (52 mmo 1),
riVztepyridine 2,. 4ILt (30 mmol) was added, the temperature was naturally raised from OC to *S, and the mixture was stirred overnight. 1OILt of dichloromethane was added to the reaction solution, and 20d of 5-hydrochloric acid was added.
After washing with water three times and further washing with saturated saline, the methylene chloride layer was separated and dried over anhydrous magnesium sulfate.

Hermitage T - Distill the residue under reduced pressure to make it into a large size.
2-pentamethylene acetonitrile 0.90 g (yield 36%) t-obtained 90 bp 12
0C/13 'i''or'r.

mp 4g, 5~49C-'l1-1-Nru(C1)CI-: a 1.15~
1.95 Cm, 8)i).

110Cs, 3H), 2.18-44z (m.

2H).

I) L (KBr): 35G0, 2950.2g75,
2250°175011450.1365.1285°1260, 1230. 1165. 101060c
'.

Ms = m7g (relative strength), 16B (M
++1.0.8).

124 (10), 108 (11), 107 (8G)
, 106 (21), 92 (20) C81 (23) -
80 (39) * 79 (16) C67 (16L 61
(18), 55 (11).

54 (14), 53 (11)e 43 (100)
, 42 (10), 41 (40).

39 (22), 2? (17).

Reference example 9 Acetone cyanohydrin OJ$5g (10mmo)
Massed anhydrous gropion dissolved in 10 μm of methylene and cooled with water.
, 56 g (12 mmol), followed by 1.5 g (12 mmol) of pyridine.
0aj (12 mmol) f was added, the temperature was allowed to rise naturally under ice temperature, and the mixture was stirred overnight. Add 20% methane to the reaction solution.
After washing with 130ml of 59f salt 3 times, washing with saturated saline solution, preparative fractionation with erczmethane HiIt, and anhydrous magnesium 4A acid solution. 2-Mefk for the purpose of distilling off the medium under reduced pressure and then distilling it under reduced pressure
-2-f Robionylpropane 2)! j le 0. s+g
(yield: 45 cm).

bP　　　　C70,5'I'orr.

”)i-NMR(CI)C1)) :δL15 (tt
Jx7.5) 1s.

3H), 1.74 (so 6)i), 2.34
(q.

J-7,5Hz, 2H)-I)L(neat): 3000. 2950-
2250. 1775°147G, 1420,139
0,1370°1355e 1225.1190.11
40 Bi・W3: m/z (relative ankylosis), 14
2 (M”+1.0.3).

75 (s), ss (46>, 57 (100)
C43 (9), 41 (36), 29 (43).

Reference Example 10 +1 0.85 g (10 mmol) of acetone cyanohydrin was dissolved in 10 k+1 methylene chloride, and 1122.1 g (12 mmol) of anhydrous monochloro vinegar was added under water cooling. 1.0aj (12 mmol) l of HiIJ-sin was added, and the mixture was stirred for 4 days while allowing the temperature to rise naturally from ice temperature to base temperature. Add 220 ml of dichloromethane to the reaction solution, wash 3 times with 30 ml of 5-dihydrochloric acid, wash once with 30 ml of saturated brine, and further wash 3 times with 30 ml of saturated igneous sodium hydrogen bath, and then separate the 7 layers of dichloromethane. ◎ The 7R' machine layer was reduced with anhydrous acid magnesium, and the solvent t
The remaining L that was removed by m8Ew is distilled under reduced pressure, and the target is
Served with 1.3 g (yield 81) of 2-eIcI a7toxytoquine-2 propanenitrile 〇bp 70-71
C70,5 Torr.

”)i-NMk (CL)C13): J L80
(s, 6HL 4.04(so 2)i).

L (neat): 3025-2975* 2250
s 1770t1750 (ah), 1470.141
0-1390.1370.1320.1290°123
011185.1135 pieces - 1°MS: m/z (
Relative strong K), 162 (M++1t O,5)+
161 CM”= 0.23,14g (0,6)+1
46 (1,8), 79 (15), 77 (47
).

6B (100)* 23 (6), 21
(17).

43 (35)# 42 (10), 41 (80)
.

39(12).

Reference example 11 Acetone cyanohydrin 1.0 g (IL7 mmol
) was dissolved in 30 dK of methylene chloride, and phenykf was dissolved under ice-cooling.
t7-kfk chloride 2.4g (12.8mmol)
, followed by triethylamine 1.73 aj (12,9
mm0 l) 'l was added, and the mixture was stirred for 3 hours with ice-warmed base solution. Reaction solution t5 [[Sales 30at"t'200, aJapanese food mWater 30dfWash once, and further wash with 30ILt of bound sodium carboxylate water bath solution, and then pour over anhydrous magnesium sulfate to remove the phlegm. The target 2-methyl-
2-phenylthioacetoxypropanenitrile 1.2g
(Yield 443 cm) was obtained.

bp 15 (1-160c10.7-0.8 1'o
rr*5H-NMfL (CDCI, ): δ1.65 (
45e3.58 to s-6 (s-2H) *7.17
~7.47 (%5B).

1R (neat): 3075e 3G20.2950
．． 2340°1740915B5.1470,1435
゜1390.1370,1265,1225゜12G0
,1115.1025.9753-5M8: m/x
(Relative Q[31237(M"+21' 2n.

236 CM++le 5)t 235 QA”+
32) e 168(10), 123 (ZGo).

109 (13) = 77 (12) - 65 (1G) δ
51 (12), 45 (41), 41 (1G).

Reference Example 12 200IIg (0,8
5 mmol) 1 to 5. OII
Nisol 11k, water cooling metachloroperbenzoin 12190
Misaki (0,811 mm OL, purity 80%) was added, and the temperature rose noticeably from the ice temperature to the straw temperature.-Stirred at night.Reaction-a
, add 201 Lt of nitrogen chloromethane, wash with 10% aqueous sodium thiocarbonate solution, and wash 3 times with 201 Lt of rc-compatible sodium bicarbonate aqueous solution, dry the organic layer with anhydrous magnesium sulfate, and remove solvent f: From the residue obtained, silica gel thin layer Chromadog 2 Fee (
The target 2-methyl-2-phenylsulleylacetoxypropanenitrile 165 cape (yield I477) was obtained by using a developing solvent (hexane-ethyl 1:1). ◎ l value 0.20-0.30 (dtU, hexane-
Vinegar ether 1:l) ') i-NMR (CDCI, ): δ1.65 (s,
3M) -L71(s, 3)1), 3.81 and 3.71(ABquartete Jxl 3.5)l
ie2)1)* 7.45~7.80 (m, 5)1
).

IR(neat): 3500.3075.3.010
．． 295G.

2350.1745.1475.1445°1390-
1370e 1270, 1230*12G0* 115
0* 1115e 1G9G-1050= 97551
−”.

M8: m/g (relative method 1, 253 CM
”+2.1).

252 (M++1$3), 251 (M”, 20)
184 (2'), 167 (3), 126 (13)
125 (100), 97 (22), 77 (27),
51 (20), 41 (11).

Reference Example 13 Acetone cyanotriy 0.85g (10mmol
) was dissolved in dichloromethane 20ajVcfII and cooled on ice.
Phenylacetyl chloride 1.8 g (I L7mmo
l), then 1.6 ml of triethylamine (11
, 5 mmol l) t7) After allowing the temperature to rise naturally to Q00 and stirring overnight in an Oka-Atsai, the reaction mixture was poured into 3 OIL of a saturated Namizuki sodium bath solution with ice, extracted with dichloromethane, and diluted with dichloromethane. Organic pigeons are dried and iced with 9ml of Anhydrous Ranjaku Natori.
Paper-pressure distillation is carried out from the residue left after removing the debris under reduced pressure.
The desired product, 0.64 g (yield: 32 g), of 2-methyl-2-phenyla-7propanenitrile was obtained.

bp 145-150C10,8 Torr.

')i -NM)L (CDL:l S) : a 1
．． 40 (s, 6H), 3.62 (ss 2)iL
7.28 (broads, 5H)-IR(nea
t): 3075.3050.3010.2950°2325, 1750.1605.1500°1470.
1455,1390.1370゜1350t 1255
, 1225, 112S book 970, 730.700 pieces.

MS: m7g (relative class K) I 204 cu
++1s 2)+203CM", 14), 119 (4
).

92 (9), 91 (Zoo), 65 (10)
.

41 (9), 39 (7).

Reference example 14 Acetone cyanohydro 70.85g (10mrno
1) Dissolve in 201Lt of t-dichloromethane, add 1.0g (12mmol) of diketene, then 0.94g of pyridine.
(12 mmol) was added under ice-cooling, and the mixture was stirred overnight at 'ki temperature.

Reaction 'FLt - Pour water-cooled 5s salt into 30aj and extract with dichloromethane. After washing the first layer with saturated brine, drying over anhydrous magnesium sulfate and removing pressure under bath 1k.IR residue The desired 2-acetoacetoxy-2-methylpropanenitrile (1.52 g (yield 90%)) was obtained by vacuum distillation. ◎bp 155
~160C/21 Torr.

')l-NMi also (CI)CI, ): J1.
7B (st 5tt) l Otsu 26 (13) 1) e 3
．． 4g Cm9 2) 1)-IR (nearly: 30
15.2950.2250, 1760°1725*
163G-1560-1470゜1410.13701
1365, 1320° 1260.1230, 1135,
1025°99! i, 970cm--MS: m7g (relative intensity), 168 (M
”-1,3).

126 (2), Zoo (z), ss (B).

84 (14), 70 (75), 69 (15)
.

68 (10), 58 (6) e 44 (12).

43 (Zoo), 42 (1B) #41 (16).

Example 1 Hexamethyldisilazane 0.70 aj (3,:4 mmo 1 ) was added to 3.0 a/h of tetrahydro 7 run under ice cooling.
, itebutyl lithium (177M THF eruption liquid) 1.
4JIj was added and stirred at OC for 30 minutes. In this solution, 2-acetoxy-2-methylpropanenitrile 127'f (LOmmol)C1F obtained in Reference Example 1 was added.
) to 9:.

Dorofuran 3.0aj@Liquid '1-76c was dripped in a few minutes. After stirring at -76C for 2 hours, anti-Lk was stopped by adding 1.0 dt of an aqueous ammonium chloride solution.

From the reaction mixture, the low boiling point substance IX was distilled off under reduced pressure, and the IA residue was purified by silica gel thin layer chromatography (ex: IM bath mixture chloromethane-methanol 10:1) for 111 minutes to obtain the desired product, 4- Amino-5,5-dimethyl-2
(5) 1) 104 q of white crystals of 72N, (82% aggregation) were obtained.
1:1) 2 Jl, 4tl (s, 6M), 4
．． 48 Cs, IH).

6-57 (br+, +S, -e 2H) ・IRCf
CBr): 3400. 3350 (sh
), 3220°3000.17201 1680.
166G.

1615.1600eM--M8: m/z (relative intensity), 128 (1
1”+1.6) t127 Kuninaka, 53), 112 (Z
oo).

70 (42), 66 (11), 59 (123
Calculated values for °C, H, NO: e, 56.68;
Lua, 13;N, 1LO2chi・芙拾：(,56,55;1-1.7.14;N,
10-90 Example 2 Diinoprobylamine 0.08 aj (5,7810-'mol) at 78C in 3.0 aj of tetrahydrofuran
, OV > butyl lithium (1,78MT layer solution) 0.
3m was added and stirred for 30 minutes at -7BC. In this solution, 2-methylpropanenitrile 50'I (0.44 mmol) obtained in Reference Example 1 was added.
of tetrahydrofuran 1. The mixture was slowly cooled down with OIL GT-78G, and further stirred at -78C for 3 hours. Add a self-phase ammonium chloride water bath to the reaction solution g1.
After adding Odt to stop the reaction, the low melting point material t'' was removed under reduced pressure and the resulting residue was formed into a thin layer of silica gel.
1) ll! &, target, 4-amino-5,5
-dimethyl-2(51-1)-7 white crystals with 4 horns 30
A cape (yield >60%) was obtained, which showed the same spectral data as that obtained in Example 1.

5A Example 3 0.18 J (3 Mrt, 0 bath solution) of ethylmagnesium bromide in 5.0 atj of tetrahydrofuran under water cooling, followed by 0.15 d (1 mmo i) of diinoprobylamine.
The mixture was added at t-t and stirred at the same 1M degree for 1 hour. In this bath solution, 2-acetoxy-2-methylpropanenitrile 5
0q (0.4 mmol) of tetrahydrofuran LOIL
The mixture was slowly added dropwise to the TFI solution at -78C, and further stirred at -78C to -72C for 4 hours. B1. Saturated ammonium chloride water fEIwL1. After the reaction was stopped by adding QLt, the residue obtained by distilling off the low point product under reduced pressure was separated using silica gel thin 1 Chromadog 2F (developing solvent: CI methane-methanol 10:1). The white line Le 12 Misaki was obtained. This product showed the same spectral data as that obtained in Example 1. 3 mmol), butyl lithium 9A (L7MTHF solution) 1,4 Jljl
and stirred for 1 hour at 5C to IOC. In this solution, 2-acetoquiter 2゜3-dimethyl, luputanenitrile 155'F (LOmraol) obtained in Reference Example 2 was added.
A solution of 3.0 Jlj of tetrahydrofuran was slowly added dropwise at -76C. After stirring at -76C for 36F,
Saturated ammonium chloride dilim water e*g3. The reaction was stopped with oILt. The reaction mixture and the residue obtained by distilling off the low boiling point substances under reduced pressure were separated into silica gel thin layer chromatogram 2 filler (developing solvent: dichloromethane-methanol 10:1J). White crystals of 4-amino-5-improvil-5-methyl-2(5H)-Funono (96 mPC yield, 462%) were obtained.

m9 171-172C'- 1) 1-NMR (CDCI, -DM80-d@10:
1): δ0.82 and 1.05(λd, J=6.6
Hz, 6M)* 1.42 (so 3H)s 1
．． 89 and 1.90 (2Q, J = 6.6)iz
e lH”)e 4.54 (sll)1)-6,23
(brute 2H).

IR (KBr): 33B0.3205.3000+
1730, (1su, 1700, 1665.1610゜1590.1 e 80.141S meeting 1290゜1230 kiichi 1゜MS: m/z (relative intensity) e 156 CM
”+tt 2L155 (M”, 8), 113 (11
).

112 (too)e To (23), 43 (35), 41 (12).

C,)l,sNo! Calculated value for 2es1. s+t;
) 1.8.44; 8, 9.03%・Sho T: 61.90; Rus, s rs; Average 8.97
blood.

Example 5 Tetrahydrofuran solution (1M solution) of Lidecum bistrimethyl 7lylamide in Tetonohito a7 run 3.0d
．． OaJ was added at 76G, and then 2-acetoxy-2-methyl-cundecanenitrile 1 obtained in reference 3 was added.
A solution of 0.0" F (0.42 mmol) in tetrahydrofuran 3.Od was added dropwise in a t-vp portion. After stirring at -760 to -70 G for 5 hours, 2.0 ml of a saturated aqueous solution of ammonium chloride (9M) was added to react. The reaction mixture was then distilled off under reduced pressure to remove low-boiling substances, and the resulting residue was prepared using silica gel thin-layer chromadog 2-fi (developing solvent: dichloromethane-methanol 10:1) to prepare the desired product. 4-amino-5-methyl-5-n-nonyl-2(5
) 1) - Obtained white crystals of furanone 63q (63 samples) 90mp 104~10'IC-'M-NMRCCDCl, ? DMaO-d・, 20
:1n: δ0.87 (L J-6,0Hz* aH
) + 1.24 (broad, 14HL 1.44
Cap3) 1), 1.67 (m+ 21()
, 4.65 C1゜18) # b-58 (br
u44, 2 to 4n.

IRCKj3r): 3440.3350.3225
．． 2925°2870.1735.1710.16G0
゜Is B Sam-'.

M8: m/x (relative chord lE) + 240 c
hd++t, 3)-239(M9s)e 211 (
6), 154 (11), 140 (12), 127
(21).

113 (59), 112 (Zoo, 8
5 (24), 70 (29), 43 (44).

Calculated value for c,,H,,Nu: g 70.25
;1-1.10.53;N, 5.85%.

Real lIa: (270,05; le 10.19; N,
5.81 Example 5 Tetrahydrofuran 3. In QatK-76G, a solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (1.0 Mm solution) L4jLj, and then a solution of 2-a7toxy-2-tzenylpropane product tolyl tssq (10 mmol) obtained in Reference Example 4 in tetrahydrofuran. 3.
After dropping 0ILt bath coffin with Yuriki 9 and stirring at 90-76C for 3 hours, add 3.0Jlj of saturated ammoecium chloride aqueous solution.
The reaction was stopped by adding t-. The residue obtained by removing low-boiling substances from the reaction mixture under reduced pressure was separated using silica gel thin layer chromatography (dichloromethane-methanol 10:1) to obtain the desired 4-amino- 164 d of white crystals of 5-methyl-5-7enyl-2(5)1)-furanone (yield: 87%) were obtained.

mp 69=71 G-1)1-NjdR(CIX:1,-DMSO-d'
l O: l ) Jl, 90 (io 38) * 4
．． 6B (so IH)e6.31 Cbr, InI
a 2HL 7-30 to 7.48 (Ugo 5H).

IR (KBr): 3400, 3205.1700.
1665 (sh), 1590-1580 (broa
d).

1445# 140shi 1290112B5゜1230 reference 1075-9653-'.

MS: m/z (relative %[) #191 (M
++2# l).

190 (M++1.11)t 189 (M983
), 175 (13), 174 (Zoo)e146
(22) I 121 (33), 112 (30), 1
05 (67), 103 (20).

77 (38) l To (14), 69 (17)
.

6B (14), 51 (20), 43 (72)
.

tx(42)e CIIHIINO!・0.5 f(, Calculated value for U: (:, 66.65; a 6.10; N, 7.07
%-actual value: C166.54; 6.24; approx. 6.
99 Taku Example 6 Tetraζ Dorofuran 3. Add lithium bis(trimethylsilyl)amide O tetrohydride a79n mortar (1.0M# liquid) at 76C to Qaj 0.9d (0.9mmo 1
) Then, the cy 2- in 2-acetate obtained in Reference Example 5
(6-medoxy-2-naphthyl)propanenitrile 10
0'F (0,37 mmol) of nato2hydro2
Kun λ Qad happy liquid T Yurikushi and dripping 90-Flo C 3
#Seki's stirred grade, saturated ammonium chloride aqueous solution LOat
i was added to stop the reaction. Lower boiling point than the reaction mixture
The residue obtained by removing the EEw was separated using a thin layer of silica gel (2 chloromethane-methanol 10:1) and used for the purpose. 4-Amino-5-methyl-5-(6-medokicu-2-naphthyl)-
2(5)1)-72-horned white crystals 95av (yield 95
'1l)t*Omp 206-208G-11-1-NMR (CDC1, -DM80-d'4:
1) JL97 (io 311) e 3.9 G (
Is 3)i) +4.73 (Is 18) e 6
．． 25 (br+-・a &121-1), 7.13
(m, 2l-1)t 7.50 (for 1) 1),
7.68 (so 1) 1), 7.67 (d.

J cod IL1) 1x-IH)-t 7.86 (d-J wealth Liti!, IM).

IRGCBr): 3450, 3350, 3240,
1730 (sh), 1725.1645, 1595°1
4401 1390.1370.127011220e
1200.1165 snow 1140*1020* 9
50cx-”.

M8: m/x (relative! iri-271CM"+2-
2) s27G (M++1.15) # 269 (M”
.

7G) #255 (18), 254 (Zoo).

226 (1G), 201 (10), 185 (40)
, 157 (18) Calculation gL as Cs5HtiNOs-o,zsH,o
2 Q7G, 19; Le 5.71; Nl 5.12 Actual measurement i
[: Q 70.26; Le 5.51; Ordinary 5. O3 Example 7 Lithium bisC trimethylsilyl)amide (1,0M'r) 17f in tetrazeta-dorofuran 3.1l JK-76G
ig) 1.3d (1.3 mmol) Then a tetrazeta-a7 run bath solution of t12-acetoxy-2-penzylpropaneethryl 11 BQ (0.6 mmol) obtained in Reference Example 6 3. Od-t was dripped slowly. After stirring at -760 for 2 hours, the reaction was stopped by adding saturated ammonium chloride solution 2, omtt, and the low boiling point @jX was removed under reduced pressure.The resulting residue was coated with a thin layer of silica gel. The desired 4-amino-5 was separated by chromatography (developing solvent: dichloromethane-methanol 10:1).
-White crystals of benzyl-5-methyl-2(51-1)-furanone 112 cape (yield 95S) t-obtained mp 158-161C- 1) 1-NMR (CDCI, -DMSO-d@10
:1): JL50 (1,3H)-3,37(st
2H).

4.43 (so 1ttL 6.15 (br,,4
゜2) IL 7.20 (broads, s+.

IR(KBr): 3420,3225.1715.
1700°1660~16SO(broad), 160
5゜1590.1450.1415.1300゜125
5.11701970011-'.

M8: m/z (relative strength, 203 CM)
, 6), 112(Zoo) = 91 (7) * 84
(33) #70 (15), 66 (40), 4
3 (19).

C1! H13NO! Calculated value as: c7o, 9z;)
1,6.45; to, 6.89%.

*A14 shift: C, 70, 75; Le 6.36;
N, 6.76%.

Example 8 Tetrahydrogen fan 2.3. Hexamethyldisilaza 7G, 7d (3,3 mmo 1), Ri l under ice cooling in Oaj.
n butyl lithium (1,78M THF #g) 1.
4ajt- was added and stirred for 1 hour at 5G to 1Oc. In this solution, 2-acetoxy-
2-Ethylbutane product Tolyl 155Iq (1,0rnmo
l) Tetrahydrofuran 3.0 aj solution gt-1-7
It dripped at 6c. After stirring at -760 for 3 hours, 2.0 m of saturated ammonium chloride water bath solution was added to stop the reaction. The boiling point fX was removed from the reaction mixture under reduced pressure, and the desired 4-amino-5.5 -diethyl-2
White crystals of (58)-7lanone 94q (yield 611G)
I got it.

mp 162-164C.

1) 1-NMR (CI) C1, -1) MSO-d'3
: 15 ao, B3 (L J = 7.2Hz, 6H)
*L54~L89 (m+4)i), 4.67
(s, IHL5.94 (br-, s l 2Fl
)・IR(KBr)=3425.3375,320
0.3000゜171511665t 1650.16
05゜1590tan-1゜MS: m/z (relative intensity) + 156 (M
++1# 1) 1155 ctv+, 9), 127
(18), 126 (Zoo) 184 (10), Fu 0 (14).

57 (53), 41 (12) - Cs ” s s NO! K versus f Total N (11
: c, 61-9L a 8-445N19.03%.

5! 811 shift: C, 61, 81; H, 8, 40; N
, 8.95%.

lol Mf19 Tetrahydrof2in 3.0. d, under water cooling, add 0.7 ml (3.3 mmol) of hexamethyldisilazane, and then add 1.4 L of butyllithium (1,77 M THF @ liquid).
t and stirred for 1 hour at 5C to IOC. In this solution, 2-a7toki&-2,2-pentamethyleneacetonitrile 167119 (1,0 mm) obtained in Reference Example 8 was added.
ol) tetrahydrofuran I @ solution was slowly added dropwise at -760°C. : After stirring for an hour,! i! Ammonium chloride aqueous solution 3.04
was added to stop the reaction. Lower boiling point A'4 than the reaction mixture
! The residue obtained by electrolyzing J7jt under reduced pressure was separated using p1 silica gel thin layer chromadog 2fi (developing solvent dichloromethane-methanol 10:1) to obtain the desired 4-amino-5,5-pentamethylene-2 (5H ) Hunon's white i! ! , M crystal 11 BMI (yield: 71 cm) was obtained.

m+)194.5~1915C0'')i-Nlv!R(CDCI, -DMSO-(i
'l: 1): δ1.33-1.93 (% I
Qi(), 4.48 (s.

In) + 6.56 (br=a,,2HL1H,CK
B Ri: 3400, 3200, 2950.2850゜1710.1670.1650+1600cy++-'
.

MS: rn/z (relative Q&) + 168 (
A4 medium +1+5).

167 prison juice, 38), 124 (27).

112 (16), 111 (100), 995
(32), 84 (65),
83 (10).

81 (27), 69 (20), 66
(77n.

55(16).

Calculated value for C, i-1ts NO,: C,64,
651; Bill 7.84; N8.38% *So 111i1L: C, 64, 56; l-1,
7,60; K 8.33% - M Example 10 Tetotsuhyde a7 Tsun 5.0a JlC9 Dissolve the 2-methyl-2+globioloxypropane product tolyl 26 cape (L8 x 10-'mol) obtained in Example 9. , solution t-7
Cool to 8C and add lithium bis(trimethylsilyl)
Amide (1,0MT) iF solution was added dropwise at 0.45 dt. Stir at -78C to -70C for 4 hours. om1
- In addition, the reaction was stopped, and the low-stain content was distilled off under reduced pressure. The residue was subjected to silica gel chromatography (opening solvent: dichloromethane-methanol 10:1
) to obtain the desired 4-amino-3,5,5
-trimethyl-2(5)i)-furanone white crystals 23
mg (yield 89%) 90mp 205-208C- IH-NMR (C1) CI, -f) MSO-d'
3: 1): #1.43 (s, 6)
i), 1.61 (so 3H).

5.69 (br s, 2H)-1 to 4. ,CKk3r): 3400,3230,3
000.2950°1?10.1665.1600.1
475°1430.1345.1215.1195°1
100.1oooc! 11-'.

A4S: m7g (relative 'AK) * 142 (
M++1-16).

141 in Gd, 71), 126 (Zoo).

98 (23)e 70 (16), 56 (19)
.

5s (s2), 54 (15), 43
(3sn.

Metric ftL as CIH,, NOI (M+):
m/z141.0790; Base 11111[:14LO''
! 70゜宷 Example 11 06B Tetrahydrofuran 3. Add 0.7 I*l (3.3 mmol) of hexamethyldisilazane to OILt under ice cooling.
, then butyllithium (1,7M THF solution 1fN)
,) 1.1 jt- was added and stirred at 5C to IOC for 1 hour. In this m solution, 2-chloroacetoxy-2-methylpropanenitrile 162 Misaki (obtained in Reference Ga 10) is added.
1.0 mmol) of a 3.0 aj bath solution of tetrahydrofuran was slowly lowered to rM at -76C. -From 76C-
After stirring at 660°C for 2 hours, a saturated aqueous ammonium solution was prepared.1. The reaction was stopped by adding OrJ.

The reaction mixture is mixed with a low boiling point. -Amino-3-riC! Claw-methyl-2
(5) White crystals of 1)-furanone 26q (yield 16q)
I met you.

mp 170-172C-'H-NMR (CDC 凰, -DMSO-d 1:1):
δ1.48 (s, 6tiL 6.8g (br
,s,.

2H).

IRCKBr): 3450 (sh),
3375. 3220°3000.1720.1s1
o, 1650°1600.1300,12251 11
4011040cym-'.

MS: m/z (relative strong K), 164 (3
), 163 (18), 162 (8), 161 (5
4).

148 (33), 146 (100) 1 118 (3
6), 104 (39), 82 (11).

76 (13), 75 (17n, 70
(24).

6B (21), 43 (60) − C, )(, L; INO, (M+) as calculation 1st shift:
m/z161.0242;
．． 0209夷) 1 Example 13 Water accumulates in 30Lt of Tetra ζ drawer! 3
0I+9(fiil”P50% A k , 0.63
mmOl) f was added. In this suspension, habit example 1
2-methyl-2-phenylthioacetoxypropanenitrile 100'v (0.43 mmol) obtained in 1
Noteto 9 H) 'Roaran 1.0idfI liquid, 711
1M down Yuri〈shi and r4 down 5, then 4 o'clock-Jl
XJ heat-stirred zero reaction mixture, clear gel: 4-layer chromatography (developing medium: hexane-ethyl vinegar 1:1
) to obtain the desired white crystals of 4-amino-5,5-dimethyl-3-phenylthio-2(51-1) furanone 22q (yield 22%).

mP 154.5-156.5C.

'H-NMkL (CDCI 1): d L55
(s, 6)i) , 6.66(br s 12M
)* 7.00~7.33 (m+5l-1)・IR(KBr): 3460.3325.3270,3
200゜17101164011585.14g0゜1
410.1290.1035-740aR-凰.

MS: m/z (relative 5[4j), 237
(M”+2.6).

236 αS+16L 235 (M+t
100), 220 (8), 192 (7) #17
6 (5n, 151 (10), 150 (2B)
)=149 (12)-142(43)s141(1
2) References 132 (10), 121 (24), 114 (
22), 113 (15).

110 (6), 109 (8), 105 (11), 8
6 (14), 77 (16).

68 (15), 65 (10), 51 (19).

45 (11), 43 (65n, 42 (12)
hmm.

39(15)・C1,)i,,NO,d (calculated value for M town: m/
z235.0663; Measurement flit: 23 s,
0646°5! Case 9 14 Nt-1! Tetrahydrofuran 30. In ILt, add 20 jlv of sodium hydride (pure K Ca, 50% + 0.42 m
mol was added. To this suspension, the nato-2hydrofuran λOd bath solution containing 50q (o, 2 mmol) of 2-/deru-2-phenylsulfinyl acetoxy-7propanenitrile prepared in Example 12 was slowly added dropwise under heating. The bales were heated and stirred for an additional 2 hours.

From the reaction solution, the target 4-amino-5°s-di+h-3 was purified using silica gel high-layer chromatography (& opening solvent: dichloromethane-methanol 10:1).
43 colorless crystals of -phenylsulfinyl-2(sH)-79non were obtained (yield: 486≠>1).

mp 137-138C.

1? i-NM (CI)CI, -L)MS(J-d
' 10 : 1) : δ1.41 &XU 1.5
3 (li, 6H)-7゜15 Cbr・s'', 1
)D, 7.33-7.57 (rQe 3HL 7.
57-7.90 (Kame 2H).

7.33-7.90 (br　s　　, 1)i).

1R (KMr): 3350.3200.300
0.1715°1665.1590.1580 (sh
)11480.1460.1410,13fu0°128
0.12251 1200.1160°1080.10
45 (sh), bought 10,250.

MS: m/z (relative '11 Ml1 l 251
CM”+3)t 235(5), 204 (
15), 203 (100n.

188 (32) + 160 (42), 15B (1
1), 126 (9), 125 (7).

117 (14), 11J9 (4), 86 (27)
.

7B (25L?? (17), 68 (18).

SL (18), 43 (23), 39 (10).

01! )l,,Measures for No5S: c, sf,
35; Le 5.21; N, 5.57; S, 12.76%.

"Central dictionary" value: α57.27; Le 5.111 Nt 5.4
8 p &lλ 4%+ Example 15 Sodium hydride 2
Purity of canoe in 0J'FC oil, 0.42mm
ol) 2 obtained in Reference Example 13 was added to the slurry to which 1c was added.
-Methyl-2-phenyla7tylpropanenitrile 10
A solution of 01"P in tetrahydrofuran 5ILt was slowly added to the skin under heating, and the mixture was further heated and stirred for 3 hours. The reaction solution was diluted with a thin layer of silica gel (developing bath: dichloromethane-methanol 10:1) for minutes*.
The desired colorless crystals of 4-amino-5,5-dimethyl-3-phenyl-2(5)1)-furanone (yield: 43-) were obtained.

mp 148-150C.

1) 1-NMR (CDCI, -DMSO-d' 1.
:1):δL57 (1,6H), 6.40 Cb
r.a.

z)i)t 7.15-7.65 (m, 5H).

HL(neat): 3400.3330.3000e
1700°1640.1615.1595,1500
゜1470.1425,1370,1330゜124゜1200.1155.1120゜1010.970.9
20α-1°MS: m/z (relative strong R) + 205 CM”
+2t IL204 (M”+1,15), 203 (
M”.

100), 188 (49), 160 (55) 15B
(IIL 132 (22), 118 (33),
Ii7 (63)t 115 (14n.

91 (14), 89 (24L 7? (6).

43(55)・(-12Hlz N 02 K total 31@: e,
70.92; H, 6.45; N, 6.89%.

Fruit 6111 (il: C, 70, 91; Le 6.49
; N, 6.85%.

Example 16 Sodium hydride 411q (50-pure #t in oil.

0.85 mmol) of tetrahydrofuran 30j+JM
In the suspension, 2-acedo7toxy 2 obtained in Reference Example 14 was added.
-Methylpropane nitrile 100 JIF (0,59
mmol) of tet2hydrofuran 1. The Oml solution was slowly added to the reaction solution under heating, and after heating and stirring for 12 hours, the low boiling point of the reaction solution was distilled off under reduced pressure.The residue was subjected to silica gel column chromatography (developing solvent The desired 3-acetel-4-amino-S, S-&
Colorless crystals of methyl-2(5?l)-furanone 28'+?
I got it. (Yield 28g) mp 188-189G.

"H-NMR (CDCS): J 1.56 (
so 6M), 2.46(s, 3M) + 7
．． 38 (br-s, 1M) 18.82 Cb
rastks, H()-IR(Kf3r): 3
370+ 1710-1650.1540°1360.
1320,1025 leap-1°MS: rn/z (
Relative strength L>, 169 CM+, 11).

ts4 (12)t 112 (8), 87 (67
), 86 (67)l 66 (Zoo).

4B (14), 46 (24)t 43 (19)
.

C,) Calculated value for l', iNO,; C・56.80
; Le 6.55; N, 8.28 Coma d11 value: C, 56,77; Le 6.65; N,
8.02 Example 17 Tetotsuhidokufuran 5. Od ni 7 ton cyanowig 7
A solution in which 10011f (1.2 mmol) was dissolved,
2-ketene 10 g'P C1.3 mmol) under water cooling,
l) I? , triethylamine 0.05 ilj t- was added. After stirring at ice temperature for 1 hour, 0.18 d (1,3 mol) of triethylamine was added, and the mixture was stirred for 6 hours while allowing the temperature to rise naturally from 90 degrees Celsius to cold. From the reaction solution, remove the negative points such as bathing, etc. by reducing the amount of wheat, residue, etc.
Separation was performed for 6 hours using a chromatograph (developing bath: chloromethane-methanol 10:1).
Attended colorless crystal 51Ni'. (Yield 38%). This compound showed the same spectral data as the compound obtained in Chuo7111ga16.

Claims (1)

[Claims] Manufacture of aminofuranone represented by the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ by treating a compound represented by the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ Method (in the formula, R^1
, R^2 is an alkyl or aryl group, and R^1 and R^2 can be taken together to form an alkylene group or a polymethylene group. R^3 is a hydrogen atom, a halogen atom, a lower alkyl group, an acyl group, an aryl group, an arylthio group, or an arylsulfinyl group. ).