JPH1087645A - Production of beta-aminoester - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a β-aminoester which is useful in the synthesis of amino acids and aminosaccharide derivatives by reaction of an optically active N- slufinylimine with a metal ester-enolate. SOLUTION: A compound of formula II (R is a 1-4C alkyl) is obtained by allowing a metal enolate to react with a compound of formula I in a solvent, for example, THF at -100 deg.C - room temperature. The metal enolate is, for example, lithium enolate or potassium enolate. Lithium enolate is prepared by allowing lithium diisopropylamide to react with t-butyl acetate in THF at -78 deg.C. The kinds of metal in the enolates, additives, reaction solvents are properly selected to enable high-yield production of both diastereomers of the corresponding β-aminoester in high selectivity. The functional groups in the obtained β-aminoester is properly changed to enable the formation of synthetic intermediates of homoserine, a useful amino acid and mannonojirimycin derivative, an amino acid.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing 3- (Np-toluenesulfinyl) amino-3- (2-furyl) propionic acid ester (sometimes referred to as β-amino ester). This compound is a useful synthetic intermediate in natural product synthesis.

[0002]

BACKGROUND ART In asymmetric synthesis, generally only one diastereomer can be obtained from one asymmetric source, but it is very useful if two diastereomers can be obtained from one asymmetric source. In the reduction reaction of the optically active β-ketosulfoxide and the addition reaction of the present optically active α-sulfinyl ester enolate with the imine, diastereomers of the S-isomer and R-isomer can be prepared by appropriately selecting the metal species. Can be divided.

[0003]

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[0004]

SUMMARY OF THE INVENTION An object of the present invention is to provide a method for producing a β-amino ester which is a synthetic intermediate useful in the synthesis of natural products.

[0005]

That is, the present invention provides a method of formula (1)

[0006]

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Wherein the compound of the formula (2) is reacted with a metal enolate.

[0008]

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(Wherein R represents a C _1-4 alkyl group).

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION In the present invention, C _1-4 alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, and the like.
A t-butyl group can be exemplified, but a t-butyl group is preferred. Hereinafter, the case of a t-butyl group will be described. Examples of the reaction solvent include ethers such as diethyl ether and THF. The reaction temperature is from -100 ° C to room temperature. Among metal enolates, lithium enolate is
It was prepared by allowing lithium diisopropylamide (hereinafter abbreviated as LDA) to act on t-butyl acetate in THF at -78 ° C. In addition, potassium enolate is prepared by reacting potassium hexamethyldisilazide (hereinafter abbreviated as KHMDS), and other metal enolates are prepared by preparing lithium enolate and then adding various metal species to perform metal exchange. After that, it was used for the reaction. Metals (in the present invention, represented as Met) include Li,
K, AlEt ₂ , Ti (O ⁱ Pr) _{3 and the} like are exemplified. In any case, after completion of the reaction, the desired product can be obtained by performing ordinary post-treatment. Diastereomer ratios were determined by high performance liquid chromatography. The structures of other compounds were determined from IR, NMR, and the like.

[0011]

Next, the present invention will be described in more detail with reference to examples and reference examples, but the present invention is not limited thereto.

Reference Example 1 Synthesis of (S)-(+)-2-Np-toluenesulfinyliminomethylfuran

[0013]

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Under a argon atmosphere, 5 ml of anhydrous THF (hereinafter, the reaction solvent used was an anhydrous one) was placed in a 100 ml two-necked eggplant-shaped flask dried under reduced pressure, and cooled to 0 ° C. 3.23 ml of hexamethyldisilazane (15.3 mmol
l) was added and stirred for 5 minutes, and then 10.6 ml (15.3 mmol) of a 1.44 N, n-butyllithium hexane solution was slowly added dropwise. After stirring at room temperature for 30 minutes, (S)
-(-)-Menthyl sulfinate 3 g (10.2 mmol
l) 15 ml of a THF solution was slowly added dropwise. The reaction was carried out while gradually raising the temperature to 0 ° C., the ice bath was removed, and the mixture was stirred at room temperature for 2 hours. After cooling to 0 ° C., 1.27 ml (15.3 mmol) of the just distilled furfural were added, followed by cesium fluoride quickly. After the temperature was gradually raised to room temperature, the mixture was stirred for 5 hours. After cooling in an ice bath and stopping the reaction with a phosphate buffer solution, the mixture was extracted with ethyl acetate. After drying over anhydrous sodium sulfate, it is concentrated on a rotary evaporator,
A crude product was obtained. Purification was performed by silica gel column chromatography (developing solvent, hexane: ether = 1: 1) conditioned with a 5% triethylamine hexane solution, and yellow-white crystals of (S)-(+)-2-
Np-toluenesulfinyliminomethylfuran was obtained. Yield 2.11 g (9.0 mmol), 89% yield Rf 0.4 (hexane: ether = 1: 2) ¹ H-NMR (270 MHz, CDCl ₃ ) δ 2.40 (s, 3
H), 6.47 (dd, 1H, J = 2.0,2.0Hz), 6.98 (d, 1H, J = 4.0Hz), 7.23
(d, 2H, J = 8.2Hz), 7.57 (d, 1H, J = 2.0Hz), 7.58 (d, 2H, J = 8.2H
z) IR (neat) 1610, 1540, 1470, 790, 550 cm ^-1 [α] _D ²³ +81.6 (c 0.93, CHCl ₃ )

Example 1 3- (Np-toluenesulfinyl) amino-3-
Synthesis of t-butyl (2-furyl) propionate

[0016]

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In a 30 ml two-necked eggplant-shaped flask dried under reduced pressure, a solution of 23.6 mg (0.23 mmol) of diisopropylamine in 3 ml of THF was added at −78 ° C. under an argon atmosphere.
0.13 ml of 1.74N, n-butyllithium hexane solution
(0.23 mmol), and LDA was prepared and stirred for 15 minutes, and then 26.1 mg (0.23 mg) of t-butyl acetate was added thereto.
(mmol) of a THF solution was slowly added dropwise to prepare a lithium enolate. After stirring at −78 ° C. for 30 minutes, 35 mg (0.15 mmol) of (S)-(−)-2-Np-toluenesulfinyliminomethylfuran
3 ml of a THF solution was slowly added dropwise, and the reaction was carried out while gradually raising the temperature to room temperature. After stirring for 12 hours,
The reaction was stopped using a phosphate buffer solution. After extraction with ethyl acetate, the extract was dried over anhydrous sodium sulfate. afterwards,
The mixture was concentrated on a rotary evaporator and purified by silica gel thin-layer chromatography (developing solvent, hexane: ether = 1: 1) pretreated with a phosphate buffer, to give 3- (Np-toluenesulfinyl) amino as a yellow oil. −
There was obtained t-butyl 3- (2-furyl) propionate. Yield 12.4 mg, Yield 24% Rf 0.2 (hexane: ether = 1: 2) 3S: 3R = 16: 84 R form ¹ H-NMR (270 MHz, CDCl ₃ ) δ 1.37 (s, 9
H), 2.39 (s, 3H), 2.98 (ddd, J = 6.0,9.9,2.6Hz, 2H), 4.86 (d
d, J = 6.1,7.6Hz, 1H), 4.99 (d, J = 7.6Hz, 1H), 6.33 (d, J = 1.7H
z, 2H), 7.25-7.39 (m, 3H), 7.59 (d, J = 2.0Hz, 2H) IR (neat) 3175,2975,1730,1360,1170,1060,81
0,740 cm ^-1 S-form ¹ H-NMR (270 MHz, CDCl ₃ ) δ 1.41 (s, 9
H), 2.39 (s, 3H), 2.93 (d, J = 3.5Hz, 2H), 4.67 (dd, J = 5.9,8.3
Hz, 1H), 5.14 (d, J = 8.6Hz, 1H), 6.17 (d, J = 3.3Hz, 1H), 6.26
(dd, J = 1.8,1.3Hz, 1H), 7.26-7.31 (m, 2H)

Example 2 3- (Np-toluenesulfinyl) amino-3-
Synthesis of t-butyl (2-furyl) propionate

[0019]

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In a 500 ml three-necked eggplant-shaped flask dried under reduced pressure, 60 g of an ether solution of 926 mg (9.15 mmol) of diisopropylamine was added at -78 ° C. under an argon atmosphere.
l, 2.07N, n-butyllithium hexane solution 4.42
ml (9.15 mmol) was added to prepare LDA. 1
After stirring for 5 minutes, 1045 mg of t-butyl acetate (9.0
mmol) in 60 ml of an ether solution to make lithium enolate, and after stirring for 15 minutes, 9.15 ml of a 1 M titanium chloride triisopropoxide hexane solution (9.15 m
mol) was added to perform metal conversion. After stirring for 30 minutes, 60 ml of an ether solution of 700 mg (3.0 mmol) of (S)-(-)-2-N-p-toluenesulfinyliminomethylfuran was slowly added dropwise, and the temperature was kept constant at -78 ° C. The reaction was maintained. After stirring for 2 hours, -78
The reaction was stopped at 0 ° C. with a phosphate buffer solution. After filtration through celite, the mixture was extracted with ethyl acetate and dried over anhydrous sodium sulfate. After concentration using a rotary evaporator, the residue was purified by flash chromatography on silica gel (developing solvent, hexane: ether = 1: 1) pretreated with a 5% solution of tolethylamine in hexane to give 3- (N-p-
There was obtained t-butyl toluenesulfinyl) amino-3- (2-furyl) propionate. Yield 1.03 mg, Yield 98% 3S: 3R = 1>: 99 Rf, ¹ H-NMR, IR The same as in Example 1.

Example 3 3- (Np-toluenesulfinyl) amino-3-
Synthesis of t-butyl (2-furyl) propionate

[0022]

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In the same manner as in Example 1, LDA was prepared from 46.3 mg (0.46 mmol) of diisopropylamine and 0.27 ml (0.46 mmol) of a 1.72 N, n-butyllithium hexane solution, and t-butyl acetate was prepared. 0.3mg (0.45
(mmol) in a THF solution (3 ml) to give lithium enolate. After stirring for 15 minutes, 0.48 ml (0.46 mmol) of 0.96 M diethylaluminum chloride was added, and the mixture was stirred for 30 minutes to perform metal exchange. At −78 ° C., 35 mg (0.15 mmol) of (S)-(−)-2-N-p-toluenesulfinyliminomethylfuran in THF
3 ml of the solution was slowly dropped, and the reaction was carried out while gradually raising the temperature to 0 ° C. After 4 hours, the reaction was stopped at 0 ° C. using a phosphate buffer solution. Thereafter, the same operation as in Example 1 was performed, and 3- (Np-toluenesulfinyl) amino-3
There was obtained t-butyl-(2-furyl) propionate. Yield: 17.0 mg (0.046 mmol), Yield: 31% 3S: 3R = 6: 94 Rf, ¹ H-NMR, IR are the same as in Example 1.

Example 4 3- (Np-toluenesulfinyl) amino-3-
Synthesis of t-butyl (2-furyl) propionate

[0025]

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In a 30 ml two-necked eggplant-shaped flask dried under reduced pressure, 3 ml of THF was placed at -78 ° C. under an argon atmosphere, and 0.92 ml of a 0.5 M KHMDS toluene solution (0.4 ml) was added.
6 mmol) and stirred for 15 minutes. Acetic acid there
-Butyl solution 52.3 mg (0.45 mmol) in THF solution 3
ml was added to obtain potassium enolate. Thereafter, 800 mg (4.5 mmol) of hexamethylphosphoric acid triamide was added, and the mixture was stirred for 30 minutes. Thereafter, the mixture was cooled to -100 ° C, and 35 mg (0.15 mmol) of (S)-(−)-2-Np-toluenesulfinyliminomethylfuran was dissolved in T
3 ml of an HF solution was slowly added dropwise, and the reaction was maintained at -100 ° C. to carry out the reaction. After 5 minutes, the reaction was stopped at -100 ° C with a phosphate buffer solution. Thereafter, the same operation as in Example 1 was performed, and 3- (Np-toluenesulfinyl) amino-
There was obtained t-butyl 3- (2-furyl) propionate. Yield 46.1 mg (0.13 mmol), Yield 88% 3S: 3R = 84: 16 Rf, ¹ H-NMR, IR The same as in Example 1.

Next, other examples including the above embodiment are shown in Table 1.
Shown in

[0028]

[Table 1]

Next, the reaction steps for the synthesis of (R) -homoserine, which are related to Reference Examples 2 to 4, will be described.

[0030]

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Reference Example 2 3- (Np-toluenesulfinyl) amino-3-
Synthesis of (2-furyl) -1-propanol 82.0 mg of lithium aluminum hydride (2.
16 mmol), cooled to 0 ° C., and THF 15 ml
Was added. After stirring for 10 minutes, 3% obtained in Example 2 was obtained.
-(Np-toluenesulfinyl) amino-3- (2
-Furyl) 625.5 mg of t-butyl propionate (1.8
15 ml of a THF solution (0 mmol,> 98% de) was slowly added dropwise, and the reaction was maintained at 0 ° C. while keeping the temperature constant. After stirring for 1 hour, at 0 ° C saturated aqueous sodium sulfate solution 0.6 ml
The reaction was stopped with. After filtration through celite, concentration using a rotary evaporator, and silica gel flash chromatography pretreated with a 5% solution of toluene in hexane (developing solvent, hexane: ethyl acetate =
1: 2) to give 3- (Np-toluenesulfinyl) amino-3- (2-furyl) -1-propanol. Yield 472 mg (1.69 mmol), Yield 94% Rf 0.3 (hexane: ethyl acetate = 1: 3) ¹ H-NMR (270 MHz, CDCl ₃ ) δ 1.92-2.1
5 (m, 2H), 2.35 (s, 3H), 3.59-3.68 (m, 2H), 3.95 (s, 1H), 4.70
(dd, J = 6.4,7.3Hz, 1H), 5.27 (d, J = 6.6Hz, 1H), 6.27-6.32
(m, 2H), 7.20 (d, J = 8.1Hz, 2H), 7.36 (d, J = 1.0Hz, 1H), 7.49
(d, J = 8.1Hz, 2H) IR (CHCl ₃ ) 3200, 2850, 1920, 1660, 1350, 9
70, 900, 540cm ^-1

Reference Example 3 Synthesis of 3-Amino-3- (2-furyl) -1-propanol 3-amino-3- (2-furyl) -1-propanol obtained in Reference Example 1 was placed in a 30 ml two-necked eggplant type flask.
(Np-toluenesulfinyl) amino-3- (2-
335.4 mg of furyl) -1-propanol (1.20 mm
ol), 5 ml of methanol was added, and the mixture was cooled to 0 ° C. After stirring for 10 minutes, 273.7 m of trifluoroacetic acid
g (2.40 mmol) was added thereto, and the mixture was kept at 0 ° C. and reacted. After stirring for 4 hours, methanol and trifluoroacetic acid were distilled off using a rotary evaporator and a vacuum pump. Hexane and water are added thereto, and the organic layer and the aqueous layer are separated.
9-10 and extracted with ethyl acetate. Then, it dried with anhydrous sodium sulfate and concentrated using the rotary evaporator. Silica gel thin layer chromatography pretreated with a phosphate buffer solution (developing solvent, methanol:
Purification with ethyl acetate = 1: 5) gave 3-amino-3- (2-furyl) -1-propanol as a colorless oil. Yield 136.6 mg (0.97 mmol), 81% Rf 0.2 (methanol: ethyl acetate = 1: 5) ¹ H-NMR (270 MHz, CDCl ₃ ) δ 1.85-2.0
4 (m, 2H), 3.27 (b, 3H), 3.85 (t, J = 5.3Hz, 2H), 4.14 (dd, J = 5.
1,3.3Hz, 1H), 6.12 (d, J = 3.3Hz, 1H), 6.31 (dd, J = 2.0,1.3H
z, 1H), 7.34 (dd, J = 0.7,1.0Hz, 1H)

REFERENCE EXAMPLE 4 Synthesis of homoserine The 3-serine obtained in Reference Example 3 was placed in a 30 ml two-necked eggplant type flask.
Amino-3- (2-furyl) -1-propanol 73.6
mg (0.52 mmol), 5 ml of methanol was added, and the mixture was cooled to -75 ° C and stirred. The reaction was performed while blowing ozone generated by an ozone generator into the apparatus. T
Following the progress of the reaction by LC check, 45 minutes later, T
When the raw material was exhausted by the LC check, the blowing of ozone was stopped, and argon was blown for 5 minutes to raise the temperature to room temperature. Thereafter, 3 ml of dimethyl sulfide was added, and the mixture was stirred for 3 hours, and methanol and dimethyl sulfide were distilled off using a rotary evaporator and a vacuum pump. Hexane and water were added thereto, and the organic layer and the aqueous layer were separated. The aqueous layer was concentrated using a rotary evaporator, and ion-exchange resin (Dewex50x2-100 (H ⁺ ))
Was used to obtain homoserine. Yield 18.8 mg (0.16 mmol), Yield 30% ¹ H-NMR (270 MHz, D ₂ O) δ 1.88-2.07 (m,
2H), 3.70-3.83 (m, 3H) [α] _D ²³ +8.8 (c 0.36, H ₂ O)

Next, the reaction steps relating to the conversion of mannonojirimycin to the derivative of Reference Examples 5 to 8 will be described.

[0035]

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Reference Example 5 Synthesis of t-butyl 3- (N-tosyl) amino-3- (2-furyl) propionate In a 100 ml two-necked eggplant type flask, 3- (Np-toluenesulfinyl) amino-3 was added. 798 mg of t-butyl- (2-furyl) propionate (2.28 mmol,> 98
% De), azeotropic benzene was performed three times, and the atmosphere was replaced with argon. After cooling to -20 ° C, 12 ml of methylene chloride was added. After stirring for 10 minutes, 640 mg (2.97 mmol) of m-chloroperbenzoic acid (hereinafter abbreviated as mCDBA)
13) Slowly drop 13 ml of methylene chloride solution of
The reaction was kept constant at 20 ° C. After stirring for 3 hours, the reaction was stopped using a saturated aqueous sodium hydrogen carbonate solution.
After washing with a saturated aqueous solution of sodium hydrogen carbonate, the mixture was extracted with ether. Then, it was dried with anhydrous sodium sulfate.
After concentration using a rotary evaporator, the residue was purified by flash chromatography on silica gel (developing solvent, hexane: ether = 2: 1) pretreated with a 5% triethylamine hexane solution to give 3- (N-tosyl) amino-3.
There was obtained t-butyl-(2-furyl) propionate. Yield 136.6 mg (0.97 mmol), 81% Rf 0.2 (methanol: ethyl acetate = 1: 5) ¹ H-NMR (270 MHz, CDCl ₃ ) δ 1.25 (s, 9)
H), 2.40 (s, 3H), 2.85 (dd, J = 6.3, 10.2Hz, 1H), 2.97 (dd, J =
5.6,11.2Hz, 1H), 4.79-4.86 (m, 1H), 6.02 (d, J = 3.3Hz, 1H),
6.17 (dd, J = 1.8,1.3Hz, 1H), 7.18 (d, J = 1.0Hz, 1H), 7.23 (d,
J = 1.0Hz, 1H), 7.68 (d, J = 8.2Hz, 2H) IR (neat) 3270,2980,1730,1340,1160,960cm ^-1

Reference Example 6 Synthesis of 3- (N-tosyl) amino-3- (2-furyl) propionic acid In a 30 ml eggplant-shaped flask, 3- (N-tosyl) amino-3- (2-furyl) propionic acid obtained in Reference Example 5 was added.
-Tosyl) amino-3- (2-furyl) propionic acid t
-Butyl 182.5 mg (0.50 mmol) and 10
% Ethanol solution of sodium hydroxide, and
Stirred for hours. After completion of the reaction, the mixture was adjusted to pH 3-4 with 2N hydrochloric acid and extracted with ethyl acetate. Thereafter, the extract was dried over anhydrous sodium sulfate, concentrated using a rotary evaporator, and purified by silica gel thin-layer chromatography (developing solvent, hexane: ethyl acetate: acetic acid = 90: 45: 1) to give 3-yellow crystals as pale yellow crystals. (N-tosyl) amino-3
-(2-Furyl) propionic acid was obtained. Yield 136.6 mg (0.97 mmol), 81% Rf 0.2 (hexane: ethyl acetate = 1: 4) ¹ H-NMR (270 MHz, CDCl ₃ ) δ 2.40 (s, 3)
H), 2.86 (dd, J = 6.3,10.6Hz, 1H), 2.96 (dd, J = 5.6,10.9Hz, 1
H), 4.78-4.86 (m, 1H), 5.81 (d, J = 3.3Hz, 1H), 6.17 (dd, J = 1.
8,1.3Hz, 1H), 7.18 (d, J = 1.3Hz, 1H), 7.23 (d, J = 8.2Hz, 2H),
7.67 (d, J = 8.2Hz, 2H) IR (neat) 2900, 1710, 1460, 1380, 1160, 1070cm
^-1

Reference Example 7 Synthesis of 4- (2-furyl) -4- (N-tosyl) aminobutan-2-one In a 30 ml two-neck eggplant-shaped flask, 3
25.8 mg (0.08 mmol) of-(N-tosyl) amino-3- (2-furyl) propionic acid was added, and the mixture was azeotroped with benzene. Then, the solvent was distilled off with a vacuum pump and the atmosphere was replaced with argon. 5 ml of diethyl ether was added, and the mixture was cooled to -78 ° C.
(0.42 mmol) was slowly added dropwise. The reaction was carried out while gradually increasing the temperature, and after stirring for 4 hours, the reaction was stopped using distilled water. After extraction with ethyl acetate, the extract was dried over anhydrous sodium sulfate and concentrated using a rotary evaporator. Alumina thin layer chromatography (developing solvent,
Purification with hexane: ethyl acetate = 2: 1) gave 4- (2-
Furyl) -4- (N-tosyl) aminobutan-2-one was obtained. Yield 14.0 mg (0.04 mmol), Yield 54% Rf 0.4 (hexane: ethyl acetate = 1: 1) ¹ H-NMR (270 MHz, CDCl ₃ ) δ 2.10 (s, 3
H), 2.40 (s, 3H), 2.92 (dd, J = 6.3, 11.2Hz, 1H), 3.09 (dd, J =
5.0,12.5Hz.1H), 4.75-4.82 (m, 1H), 5.56 (d, J = 1.2Hz, 1H),
5.96 (d, J = 3.3Hz, 1H), 6.15 (dd, J = 2.0,1.3Hz, 1H), 7.15 (t,
J = 0.9Hz, 1H) .7.23 (d, J = 8.1Hz, 2H), 7.67 (d, J = 8.1Hz, 2H) IR (neat) 3400,1640,1330,1160,810,750cm ^-1

Reference Example 8 Synthesis of dihydropyridinone 4- (2-furyl) -4 was placed in a 10 ml Hertz flask.
13.0 mg of-(N-tosyl) aminobutan-2-one
(0.04 mmol) was added, and the mixture was azeotroped with benzene. Thereafter, the solvent was distilled off with a vacuum pump and the atmosphere was replaced with argon. 1 ml of methylene chloride was added, the mixture was cooled to 0 ° C., and 2.0 mg of mCPBA was added.
(0.09 mmol) of a methylene chloride solution (1 ml) was slowly added dropwise. The reaction was carried out while gradually increasing the temperature, and after stirring for 4 hours, the reaction was stopped using a saturated aqueous solution of sodium hydrogen carbonate. After washing with a saturated aqueous solution of sodium hydrogen carbonate, the mixture was extracted with ether. Thereafter, the extract was dried over anhydrous sodium sulfate and concentrated using a rotary evaporator to obtain dihydropyridinone. Yield (Crude) 17.7 mg, Yield 40% Rf 0.2 (hexane: ethyl acetate = 1: 1) ¹ H-NMR (270 MHz, CDCl ₃ ) δ 2.07 (s, 3)
H), 2.42 (s, 3H), 3.32 (dd, J = 4.6,37.6Hz, 2H), 4.94 (t, J = 4.
6Hz, 1H), 5.95 (d, J = 4.6Hz, 2H), 6.10 (d, J = 9.6Hz, 1H), 6.97
(dd, J = 4.9,5.3Hz, 2H), 7,30 (d, J = 8.3Hz, 2H), 7.60 (d, J = 8.
3Hz, 2H) IR (neat) 2340, 1960, 1690, 1030, 810cm ^-1

[0040]

EFFECTS OF THE INVENTION In the addition reaction of an optically active N-sulfinyl imine with a metal ester enolate, by appropriately selecting the metal species of the enolate, additives and the reaction solvent, both diastereomers of the corresponding β-amino ester can be obtained. The compound could be obtained with high yield and high selectivity. The obtained β-
By converting the functional group of the amino ester, it can be applied to a synthetic intermediate of a derivative of the useful amino acid homoserine and the amino sugar mannojirimycin, which is useful in organic synthesis.

Claims (1)

[Claims] (1) Formula (1) Wherein a metal enolate is reacted with the compound of the formula (2): (Wherein, R represents a C _1-4 alkyl group).