JPH0617342B2 - Method for producing optically active β-amino alcohol - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention has the general formula (III) The method for producing an optically active β-amino alcohol represented by, more specifically, an optically active β-amino alcohol which can be easily produced from an acid addition salt of an optically active α-amino acid halide by a two-step simple reaction operation. Manufacturing method.

Optically active β-amino alcohol, for example (1R, 2S) -2-
Amino-4-methyl-1-phenylpentan-1-ol is an intermediate that can be induced in medicine and agriculture (Japanese Patent Application No. 59-203623) and (1R, 2S) -2-amino-1. , 2-
Diphenylethan-1-ol is useful as an optical resolving agent. Further, (1R, 2S) -2-amino-1-phenylpropane- which is an optically active β-amino alcohol.
1-ol (l-norephedrine) is useful by itself as a sympathomimetic agent.

This l-norephedrine protects the amino group of (1) an optically active amino acid with a protecting group [hereinafter, this may be abbreviated as "N-protection". ], (2) N-protected optically active amino acid as N-protected optically active amino acid halide,
(3) N-protected optically active amino acid halide and benzene are converted into N-protected optically active α-aminoketone by Friedel-Crafts reaction, and (4) this N-protected optically active α-aminoketone is reduced to give N-protected optically active. It can be produced by using β-amino alcohol and (5) removing the protecting group.

A phthalyl group [A. M. Beckett et al., Tetrahedron, 21 , 1489 (1965); AMBecke
tt, et al., Tetrahedron, 21 , 1489 (1965)], ethoxycarbonyl group [tee. F. Buckley III et al., Journal of the American Chemical Society, 10
3, 6157 (1981); TFBuchley III et al, J. Am. Chem. So
c., 103, 6157 (1981)] and the like are known.

However, the above-mentioned method for producing 1-norephedrine has the following problems.

It is not industrially advantageous since it requires a step of introducing a protecting group into the amino group of the optically active amino acid and a step of removing the protecting group from the amino group after reduction of the N-protected α-aminoketone.

However, when the protecting group is a trifluoroacetyl group, the protecting group can be eliminated simultaneously with the reduction of the carbonyl group.

However, no matter what protecting group, the stereoselectivity (erythro / threoselectivity) in the reduction of the carbonyl group is poor, and β-aminoalcohol with high optical purity cannot be produced.

Therefore, the above method requires a step of separating diastereomers.

Since the known method for producing 1-norephedrine has the above-mentioned problems, the method for producing (1R,
Other optically active β-amino alcohols such as (2S) -2-amino-4-methyl-1-phenylpentan-1-ol and (1S, 2R) -2-amino-1,2-diphenylethane-1-ol Even if it is applied to the manufacturing method, the above problems still exist.

Therefore, the object of the present invention is to solve the problems in the conventional methods described above, to introduce no special protection, and
It is an object of the present invention to provide an efficient method capable of producing an optically active β-aminoalcohol with high selectivity to an erythro body by a simple two-step synthetic operation from an acid addition salt of an amino acid halide.

That is, the present invention has the general formula (In the formula, X represents a halogen atom, R ¹ represents an alkyl group or a phenyl group, R ² represents a hydrogen atom or a lower alkyl group, or R ¹ and R ² jointly adjoin adjacent carbon atoms. Represents a five-membered ring formed together with a nitrogen atom, * represents an asymmetric carbon, and benzene is reacted with the compound represented by the general formula (In the formula, R ¹ , R ² , X and * are the same as those described above.), And the compound is then reduced with sodium borohydride. (In the formula, R ¹ , R ² and * are the same as the above.) The method for producing an optically active β-aminoalcohol.

The acid addition salt of the optically active α-amino acid halide represented by the general formula (I) can be prepared by a known method [K. Dee. Coppler et al., Journal of the American Chemicals
Society, 78, 6199 (1956), KDKopple et al, J.Am.Ch
em.Soc., 78 , 6199 (1956)] or according to this known method.

The optically active α-amino acid used as a raw material may be either L-form or D-form.

Here, as R ¹ in the general formula (I), specifically, a methyl group, an ethyl group, a propyl group, an isopropyl group,
Butyl group, isobutyl group, t-butyl group, pentyl group,
Hexyl, heptyl, octyl, etc. have 1 carbon atom
8 alkyl group, and a phenyl group, wherein specifically, a hydrogen atom as R ² or the R ¹ Similarly the lower alkyl group and the like and, furthermore, the R ¹ and R ²
And a carbon atom and a nitrogen atom adjacent to them jointly form a five-membered ring. Among these, preferable R ¹ is a lower alkyl group having 1 to 4 carbon atoms and a phenyl group, R ² is a hydrogen atom, and further, R ¹ and R ² are carbon atoms adjacent to them. And a nitrogen atom together form a five-membered ring.

As the halogen atom X in the general formula (I), a chlorine atom and a bromine atom are preferable, and a chlorine atom is particularly preferable.

The acid addition salt of the α-amino acid halide represented by the general formula (I) is prepared by a known method or according to this known method without isolation and purification, and the following reaction mixture is used as it is. It can also be used in the Friedel-Crafts reaction.

The acid addition salt of the optically active α-aminoketone represented by the general formula (II) is the optically active α-aminoketone represented by the general formula (I).
It can be obtained by Friedel-Crafts reaction of an acid addition salt of an amino acid halide with benzene.

As the solvent in the Friedel-Crafts reaction, those commonly used in this type of reaction can be used, benzene as a reaction substrate can also be used as a solvent, and nitromethane, carbon disulfide, etc. can also be used. It can also be used.

As the Lewis acid as the catalyst, for example, one kind of anhydrous aluminum chloride, tin tetrachloride, boron trifluoride, zinc chloride, titanium chloride or the like or a mixture of two or more kinds thereof can be used. Among these Lewis acids, anhydrous aluminum chloride and the like are preferable.

The amount of the Lewis acid used is usually, based on the acid addition salt of the optically active α-amino acid halide represented by the general formula (I),
The amount is 2 to 10 times mol, preferably 2 to 3 times mol.

The reaction temperature in the Friedel-Crafts reaction is 50-100.
At C, the reaction time is 2 to 6 hours.

The reaction product obtained by this Friedel-Crafts reaction can be purified by a conventional method to obtain the acid addition salt of the optically active α-aminoketone represented by the general formula (II).

Then, the acid addition salt of the optically active α-aminoketone represented by the general formula (II) is converted to the α-amino alcohol represented by the general formula (III) by a reduction reaction.

The reaction is alcohols such as methanol and ethanol,
It can be carried out in a solvent such as ethers such as tetrahydrofuran.

The reaction temperature in the reduction reaction is in the range of -5 ° C to + 15 ° C.

The amount of sodium borohydride used is determined by the above general formula (II).
The molar amount is 0.5 to 1 times that of the acid addition salt of the optically active α-aminoketone.

The reaction product containing the optically active β-amino alcohol thus obtained is subjected to usual isolation and purification operations,
The optically active β-amino alcohol represented by the general formula (III) is isolated.

The typical optically active β-amino alcohol obtained by the method of the present invention is listed below.

Compound 1; (1R, 2S) -2-Amino-1-phenylpropan-1-ol (l-norephedrine) Compound 2; (1R, 2S) -2-Amino-3-methyl-1-phenylbutane-1 -Ol compound 3; (1R, 2S) -2-amino-4-methyl-1-phenylpentan-1-ol compound 4; (1S, 2R) -2-amino-1,2-diphenylethane-1-ol Compound 5; (R) -phenyl [(S) -pyrrolidin-2-yl] methanol Compound 6; (1S, 2R) -2-Amino-1-phenylhexan-1-ol Compound 7; (1S, 2R) 2-Amino-1-phenylheptane-1-ol compound 8; (1S, 2R) -2-amino-1-phenyloctane-1-ol compound 9; (1S, 2R) -2-amino-1-phenylnonane -1-ol compound 10; (1S, 2R) -2-amino-1-phenyldecane-1-ol The Shimesuru is part of an optically active β- amino alcohol obtained by the method according to the present invention, it is needless to say the not intended to be limited to the illustrated.

The optically active β-amino alcohol obtained by the method of the present invention is used as a drug such as 1-norephedrine, an optical resolving agent, or an asymmetric synthesis assistant.

Further, the optically active β-amino alcohol has, for example, the following reaction formula: (However, in the reaction formula, *, R ¹ , R ² and X have the same meanings as described above, R ³ and R ⁴ each represent the same or different lower alkyl group, or R ³ and R ⁴ Forms a 5- to 7-membered ring with the adjacent nitrogen atom. N is 2 or 3.), and can be induced to an aminoalcohol derivative (IV) having a glutamate-blocking action or a central nervous system relaxing action. (See Japanese Patent Application No. 59-203623). This amino alcohol derivative (IV) is used not only as a medicine or pesticide, but also for example (Provided that *, R ¹ , R ³ , R ⁴ and n have the same meanings as described above, and Y represents a halogen atom or a trichloromethyloxy group.) And thus have a glutamate blocking action and a central muscle relaxing action. It can be induced to a 1,3-oxazolidin-2-one derivative (V).

According to the present invention, (1) it is possible to omit the step of protecting the amino group of the optically active α-amino acid with a protecting group, and the step of removing the protecting group, as in the prior art, (2) industrially By using sodium borohydride which is an available reducing agent, it is possible to produce an optically active β-amino alcohol with high erythroselectivity of 95% or more, and (3) optically active sodium borohydride. When the carbonyl group in the acid addition salt of an α-aminoketone and an acid is reduced, the acid is neutralized, eliminating the need for a special step of removing the acid from the addition salt. (4) After all, the optically active α-amino acid When used as a raw material, an optically active β-aminoalcohol having a number of excellent advantages such as being capable of producing an optically active β-aminoalcohol with high optical purity in a three-step reaction operation. It is possible to provide a manufacturing method.

(Example 1) Production of (S) -2-aminepropiophenone hydrochloride 14.1 g of anhydrous aluminum chloride was suspended in 55 ml of dry benzene, and 7.64 g of L-alanyl chloride hydrochloride was added thereto with stirring at room temperature. After that, it was heated to 50-60 ° C. for 1 hour and further heated to reflux temperature for 2.5 hours. The cooled reaction mixture was poured into a mixture of 158 g of ice and 17.7 ml of concentrated hydrochloric acid. The aqueous layer was separated, 68 ml of concentrated hydrochloric acid was added, the mixture was concentrated under reduced pressure at 50 ° C. or lower until crystals began to precipitate, and the crystals obtained by standing at 5 ° C. for 1.5 hours were collected by filtration, Wash with acetone and ether. White crystalline title compound 5.75 after drying under reduced pressure
g (yield 58.3%) was obtained. The physical properties of the title compound recrystallized from ethanol / ether are as follows.

mp; 175-176 ° C, NMR (CDCl ₃ / CD ₃ OD = 10/1) δ (ppm); 1.64 (3H, d, J = 7 Hz, C H ₃ ) 5.14 (1H, q, J = 7 Hz, C H CH ₃ ) 7.28 to 8.12 (5H, m, Aromatic Hydrogen) (1R, 2S) -2-Amino-1-phenylpropan-1-ol [l-Norephedrine] Production of (S) -2-Aminopropiophenone Hydrochloride in 10 ml of Methanol 930 mg of the salt was dissolved, and 95 mg of sodium borohydride was added while cooling to 10 ° C or lower. After stirring at the same temperature for 30 minutes, the reaction mixture was concentrated under reduced pressure. To the concentrated residue, 10 ml of chloroform, 2.5 ml of water, and then 2.5 ml of 2N aqueous sodium hydroxide solution were added and stirred. The separated organic layer was washed with 5 ml of saturated saline and dried over sodium sulfate, and the solvent was distilled off to obtain 735 mg of the title compound as white crystals. Its physical property values are as follows _{NMR (CD Cl 3) δ (} ppm); 0.95 (3H, d, J = 6Hz, C H 3) 2.05 (3H, broad s, O H, N H 2) 2.94~ 3.30 (1H, m, C H NH ₂ ) 4.51 (1H, d, J = 5 Hz, C H OH) 7.30 (5H, m, aromatic hydrogen) After obtaining 735 mg of 1-norephedrine obtained as a hydrochloride, The crystals were recrystallized from ethanol / isopropyl ether (yield: 662 mg), and the melting point, specific illuminance and IR were measured.

Identification data of l-norephedrine hydrochloride mp; 171-172 ° C In addition, when the hydrochloride 1-norephedrine was induced into an acid amide with an optically active acid, Mosher acid, and analyzed by high performance liquid chromatography (HPLC), the optical purity was 98% or more.

(Example 2) (S) -2-Amino-3-methyl-1-phenylbutane-
Preparation of 1-one hydrochloride 14.1 g of anhydrous aluminum chloride was suspended in 55 ml of dry benzene, and L-valyl chloride hydrochloride was stirred at room temperature.
After adding 9.12 g, it was heated to 50-60 ° C. for 1 hour and then to reflux temperature for 3 hours. The cooled reaction mixture is then cooled to ice 212
g and 18 ml of concentrated hydrochloric acid, and stirred for 30 minutes. The aqueous layer was separated, the organic layer was extracted with 60 ml of water, the extracted water and the aqueous layer were combined, and 68 ml of concentrated hydrochloric acid was added thereto,
Concentrate under reduced pressure below 50 ° C until crystals precipitate, then 5 ° C
After standing for 2 hours below, the precipitated crystals were collected by filtration, washed with ether, and then dried under reduced pressure to give the title compound as white needles.
7.61 g (yield 67.2%) was obtained. The physical properties of the title compound recrystallized from isopropanol are as follows.

mp; 209 ~ 211 ℃ (decomposition) NMR (CD Cl ₃ / CD ₃ OD = 10/1) δ (ppm) 0.91 (3 H, d, J = 7 Hz, C H ₃ ) 1.18 (3 H, d, J = 7 Hz, C H ₃ ) 2.12 to 2.64 ( 1H, m, C H (CH ₃ ) ₂ ) 5.04 (1H, d, J = 4 Hz, C H NH ₂ ) 7.32 to 8.12 (5H, m, aromatic hydrogen) (1R, 2S) -2-amino-3 -Methyl-1-phenylbutan-1-ol production (S) -2-amino-3-methyl-1- in 33 m of methanol
Dissolve 3.21 g of -phenylbutan-1-one hydrochloride,
Sodium borohydride 284mg while cooling below ℃
Was added. After stirring at the same temperature for 30 minutes, the reaction mixture was concentrated under reduced pressure. Chloroform (20 ml), water (8 ml) and a 2N aqueous solution of caustic soda (8 ml) were added to the concentrated residue and stirred. The organic layer was separated, washed with saturated brine, dried over sodium sulfate, and the solvent was evaporated to give white crude crystals which were recrystallized from ethyl acetate / n-hexane to give white crystals. 1.99 g (yield 74.0%) of the title compound was obtained. The physical property values are shown below.

mp; 72-73 ℃ NMR (CD Cl ₃ ) δ (ppm): 0.88 (3H, d, J = 7Hz, C H ₃ ) 1.00 (3H, d, J = 7Hz, C H ₃ ) 1.2 to 2.0 (4H, m, CH (CH _{3) 2, N H 2,} O H) 2.73 (1H, dd, J = 6,6Hz, C H NH 2) 4.58 (1H, d, J = 6Hz, C H OH) 7.32 (5H, m, aromatic Hydrogen) The obtained (1R, 2S) -2-amino-3-methyl-1-phenylbutan-1-ol was derivatized into an acid amide with Mosher acid and analyzed by high performance liquid chromatography (HPLC). The optical purity was 99% or more.

(Example 3) Production of (S) -2-amino-4-methyl-1-phenylpentan-1-one hydrochloride 3.0 g of dry benzene was suspended, cooled to about 10 ° C. and stirred while stirring. -197 g of leucine was added and stirred at 10-20 ° C for 4 hours. Then, while cooling to about 5 ° C., 600 g of anhydrous aluminum chloride was added. The reaction mixture was gradually heated, raised to the reflux temperature over 2 hours, and further heated under reflux for 2 hours. After cooling, the reaction mixture was cooled with 3.0 kg of ice and 450 mL of concentrated hydrochloric acid.
Poured with stirring into a mixture with ml. Then, the aqueous layer was separated, the organic layer was extracted with water (1.0 l once, 0.2 l once), the extract was added to the first separated aqueous layer, and the mixture was allowed to stand overnight. The precipitated crystals were collected by filtration, washed with ether, and dried under reduced pressure to give 254 g of the title compound as white crystals (yield 75.0%).
%). The physical properties of the title compound recrystallized from isopropanol are as follows.

mp; 206-208 ℃ (decomposition) NMR (CD Cl ₃ / CD ₃ OD = 10/1) δ (ppm: 0.95 (3H, d, J = 6Hz, C H ₃ ) 1.10 (3H, d, J = 6Hz, C H ₃ ) 1.50 to 2.10 ( _{3H, m, C H 2 CH} (CH 3) 2) 5.07 (1H, t, J = 7Hz, C H NH 2) 7.32~8.12 (5H, m, aromatic hydrogen) (1R, 2S) -2- amino Preparation of -4-methyl-1-phenylpentan-1-ol 3.0S of methanol in (S) -2-amino-4-methyl-1-
Dissolve 254 g of phenylpentan-1-one hydrochloride,
56.7 g of sodium borohydride was added while cooling to below ℃. After stirring at the same temperature for 30 minutes, the reaction mixture was concentrated under reduced pressure. Chloroform 1.5 l, water 0.7 in the concentrated residue
5 liters and subsequently 0.75 liter of 2N aqueous sodium hydroxide solution were added and stirred. The organic layer was separated, washed with saturated brine, dried over sodium sulfate, and the solvent was distilled off to give white crude crystals which were recrystallized from n-hexane to give white needle crystals. Compound
178 g (yield 81.9%) was obtained.

The physical properties are as follows.

mp; 70-71 ℃ NMR (CDCl ₃ ) δ (ppm): 0.81 (3H, d, J = 9Hz, C H ₃ ) 0.87 (3H, d, J = 6Hz, C H ₃ ) 0.94 to 1.84 (3H, m, CH ₂ C H _{(CH 3) 2) 2.02 (} 3H, broad s, N H 2, O H) 2.84~3.14 (1H, m, C H NH 2) 4.49 (1H, d, J = 5Hz, C H OH) 7.28 (5H , M, aromatic hydrogen) The obtained (1R, 2S) -2-amino-4-methyl-1-phenylpentan-1-ol was derivatized into an acid amide with Mosheric acid to perform high performance liquid chromatography. As a result of graph (HPLC) analysis, the optical purity was 99% or more.

(Example 4) Production of (R) -2-amino-1,2-diphenylethan-1-one hydrochloride 12.2 g of anhydrous aluminum chloride was suspended in 46 ml of dry benzene, and D-α-phenylphosphide was stirred at room temperature. After adding 9.38 g of enilglycyl chloride hydrochloride, with stirring 50-60
The mixture was heated to 0 ° C for 1 hour and then to reflux temperature for 3 hours. Then
The cooled reaction mixture was poured into a mixture of 500 g of ice and 15 ml of concentrated hydrochloric acid, 150 ml of ether was further added, and the mixture was stirred for 1 hour. The aqueous layer was separated, concentrated hydrochloric acid (50 ml) was added, the mixture was concentrated under reduced pressure at 50 ° C or lower until crystals began to precipitate, and then allowed to stand for 2 hours under cooling. 6.07 g (yield 53.9%) of the title compound was obtained as yellow crystals. The physical properties of the title compound recrystallized from ethanol are as follows.

mp; 228 ~ 230 ℃ (decomposition) _{NMR (CD Cl 3 / CD 3} OD = 3/1) δ (ppm): 6.18 (1H, s, C H NH 2) 7.24~7.68 and 7.80~8.08 (10H, m, aromatic hydrogen) (1S, 2R ) -2-Amino-1,2-diphenylethan-1-ol production 1.24 g of (R) -2-amino-1,2-diphenylethan-1-one hydrochloride was dissolved in 12 ml of methanol and stirred under ice cooling. While adding 95 mg of sodium borohydride. After stirring for 30 minutes while cooling below 10 ° C., the reaction mixture was concentrated under reduced pressure. Chloroform 20 ml, water 2.
5 ml and subsequently 2.5 ml of 2N aqueous sodium hydroxide solution were added and stirred. The organic layer was separated, washed with saturated brine, dried over sodium sulfate, and the pale yellow crude crystals obtained by distilling off the solvent were recrystallized with 95% ethanol to give white needle crystals. 760 mg (yield 71.1%) of the title compound was obtained.

The physical property values are shown below.

mp; 142.5-143.5 ℃ _{NMR (CDCl 3) δ (ppm} ): 1.85 (3H, broad s, N H 2, O H) 4.10 (1H, d, J = 6Hz, C H NH 2) 4.70 (1H, d, J = 6Hz, C H OH) 7.23 (10H, m, aromatic hydrogen) The obtained (1S, 2R) -2-amino-1,2-diphenylethan-1-ol was converted into an acid amide with Mosheric acid to accelerate the reaction. When analyzed by liquid chromatography (HPLC),
The optical purity was 99% or more.

(Example 5) Method for producing phenyl [(S) -pyrrolidin-2-yl] methanone hydrochloride 20.9 g of phosphorus pentachloride was suspended in 200 ml of dry benzene,
After adding 11.5 g of L-proline with stirring at room temperature, the mixture was stirred at room temperature for 4 hours. After cooling the reaction mixture, 40.0 g of anhydrous aluminum chloride was added. Then, the reaction mixture was gradually heated with stirring, raised to the reflux temperature over 2 hours, and further heated under reflux for 2 hours. The cooled reaction mixture is then poured into a mixture of 200 g of ice and 30 ml of concentrated hydrochloric acid, 3
Stir for 0 minutes. The aqueous layer was separated and concentrated under reduced pressure at 50 ° C or lower. The concentrate was extracted three times with chloroform, the extract was dried over sodium sulfate, and the solvent was evaporated under reduced pressure to obtain 10.9 g (yield 51.5%) of the title compound as light yellowish brown crystals. ethanol/
The physical properties of the title compound recrystallized from ether are shown below.

mp; 174-176 ℃ (decomposition) NMR (CDCl ₃ ) δ (ppm); 1.68 to 2.96 (4H, m, 3.32 to 3.90 (2H, m, 5.36-5.76 (1H, m, 7.20 to 8.08 (5H, m, aromatic hydrogen) (R) -phenyl [(S) -pyrrolidin-2-yl] methanol production method 10% methanol containing phenyl [(S) -pyrrolidine-2-
Ilyl] methanone hydrochloride (1.06 g) was dissolved, and sodium borohydride (95 mg) was added with stirring under ice cooling. After stirring at 10 ° C. or below for 30 minutes, the anti-lead mixture was concentrated under reduced pressure.
To the concentrated residue, 10 ml of chloroform, 2.5 ml of water, and then 2.5 ml of 2N aqueous sodium hydroxide solution were added and stirred. The organic layer was separated, washed with saturated brine, dried over sodium sulfate and evaporated to remove the solvent to give a crude product of the title compound as a yellow oil.
0.89 g was obtained.

The physical property values are shown below.

NMR (CDCl ₃ ) δ (ppm): 1.24 to 1.88 (4H, m, 2.64 to 3.08 (4H, m, 3.12 to 3.44 (1H, m, 4.69 (1H, d, J = 5Hz, C H -OH) 7.31 (5H, m, aromatic hydrogen) obtained (R) - phenyl [(S) - pyrrolidin-2-yl]
0.89 g of methanol was used as a hydrochloride, and then recrystallized from a mixed solvent of ethanol / ethyl acetate (yield: 802 mg, white scaly crystals). The physical properties of (R) -phenyl [(S) -pyrrolidin-2-yl] methanol hydrochloride are shown below.

mp; 156-157 ℃ In addition, when the (R) -phenyl [(S) -pyrrolidin-2-yl] methanol hydrochloride was derivatized into an acid amide with Mosher acid and analyzed by high performance liquid chromatography (HPLC), the optical purity was found to be It was over 99%.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (56) References J. Prakt. Chem. , 313 (1), 1-16 ('71) Zn. Org. Khim. , 21 (5), 983-990 ('85)

Claims (2)

[Claims] 1. A general formula (In the formula, X represents a halogen atom, R ¹ represents an alkyl group or a phenyl group, R ² represents a hydrogen atom or a lower alkyl group, or R ¹ and R ² jointly adjoin adjacent carbon atoms. Represents a five-membered ring formed together with a nitrogen atom, * represents an asymmetric carbon, and benzene is reacted with the compound represented by the general formula (In the formula, R ¹ , R ² , X and * are the same as those described above.), And the compound is then reduced with sodium borohydride. (In the formula, R ¹ , R ² and * are the same as the above.) The method for producing an optically active β-amino alcohol. 2. The method for producing an optically active β-amino alcohol according to claim 1, wherein X is chlorine.