公开(公告)号：JPH06107604A

公开(公告)日：1994-04-19

申请号：JP26041892

申请日：1992-09-30

Applicant: TORAY INDUSTRIES

Inventor： NAKAI SAKIE ,  SATOU HARUYO

IPC: C07B57/00 ,  C07C209/88 ,  C07C211/29

Abstract: PURPOSE:To carry out optical resolution of a (RS)-1-(4-halogenophenyl) ethylamine in an industrially advantageous way using, as optically resolving agent, a stable, specific optically active compound which can be obtained in high yield from inexpensive raw material(e). CONSTITUTION:Using, as optically resolving agent, a compound selected from optically active N-benzenesulfonylglutamic acid, optically active N- formylphenylglycine, optically active phenylsuccinic acid and optically active tartaric anilide derivatives of formula I (R is chlorine, methoxy or nitro), a (RS)-1-(4-halogenophenyl)ethylamine of formula II (X is chorine or bromine) is brought into contact with the above optically resolving agent in a solvent to produce diastereomer salts. Then, the solution containing the diastereomer salts is either cooled or concentrated to crystallize the sparingly soluble diastereomer. The remaining mother liquor after separating the above diastereomer salt is either cooled or concentrated again to deposit the readily soluble diastereomer salt which is then separated from the liquor. The optically resolving agent used, which is sparingly soluble in water, can be recovered in high yield and reused.

公开(公告)号：JPH06100502A

公开(公告)日：1994-04-12

申请号：JP25171592

申请日：1992-09-21

Applicant: TORAY INDUSTRIES

Inventor： NAKAI SAKIE ,  SATOU HARUYO

IPC: C07B57/00 ,  C07C209/88 ,  C07C211/30

Abstract: PURPOSE:To resolve (RS)-1-(1-naphthyl)ethylamine in excellent yield and optical purity by using a specific optically active tartaric acid anilide obtained from inexpensive raw material in high yield and capable of industrially feeding as a resolving agent. CONSTITUTION:An optically active tartaric acid anilide derivative (e.g. o-nitro- tartaric acid anilide or p-methoxy-tartaric acid anilide) of the formula (R is methoxy or nitro) as a resolving agent is brought into contact with (RS)-1-(1- naphthyl)ethylamine in a solvent to prepare a sparingly soluble diastereomer salt. Then, a solution of the salt is cooled and/or concentrated to crystallize and separate the sparingly soluble diastereomer salt from the solution. On the one hand, residual mother liquor is cooled and/or concentrated to deposit and separate a readily soluble diastereomer salt from the liquor. Since the optically active tartaric acid anilide derivative of the formula used as the resolving agent is sparingly soluble in water, it can be recovered in high yield from the diastereomer salt solution, and is hardly decomposed or racemized in a recovery process.

公开(公告)号：JPH05194330A

公开(公告)日：1993-08-03

申请号：JP873892

申请日：1992-01-21

Applicant: TORAY INDUSTRIES

Inventor： FUJINO TOSHIHIRO ,  SATOU HARUYO

IPC: B01J31/28 ,  C07B61/00 ,  C07C209/10 ,  C07C211/52

Abstract: PURPOSE:To produce 3,5-dichloroaniline from 1,3,5-trichlorobenzene in a high selectivity without requiring a complicated post-treatment. CONSTITUTION:When 1,3,5-trichlorobenzene is reacted with ammonia in the presence of a copper catalyst to produce 3,5-dichloroaniline, the reaction is performed in the coexistence of N-methyl-epsilon-caprolactam or 2-pyrrolidone.

公开(公告)号：JPH0474165A

公开(公告)日：1992-03-09

申请号：JP18645890

申请日：1990-07-13

Applicant: TORAY INDUSTRIES

Inventor： ITO NORIKO ,  SATOU HARUYO

IPC: C07D213/38 ,  A61K31/44 ,  A61K31/4402 ,  A61K31/4418 ,  A61P43/00 ,  C07B57/00

Abstract: PURPOSE:To enable reutilization of a resolving agent and obtain the subject compound which is a medicine in high purity by optically resolving dl-1-(p- chlorophenyl)-1-(2-pyridyl)-3-dimethylaminopropane using the specific readily available resolving agent. CONSTITUTION:dl-1-(p-Chlorophenyl)-1-(2-pyridyl)-3-dimethylaminopr p-ane is optically resolved by using a benzenesulfonyl derivative of an optically active amino acid expressed by the formula (n is 0 or 1) as a resolving agent to afford the objective compound. As specific procedures, the aforementioned compound is initially brought into contact with the resolving agent in an amount of 0.5-3.0 mol, preferably 1.0-2.5 mol based on 1 mol aforementioned raw material in a solvent to prepare a diastereomer salt. At this time, 0.1-1.5 mol mineral acid such as hydrochloric acid or organic acid such as acetic acid may coexist there in. The resultant solution containing the formed diastereomer salt is then cooled, concentrated and separated to afford the objective compound. Furthermore, the above-mentioned resolving agent is obtained by, e.g. slowly adding benzenesulfonyl chloride dissolved in a solvent to an aqueous solution of an optically active amino acid regulated to pH 10.

公开(公告)号：JPH0418057A

公开(公告)日：1992-01-22

申请号：JP29478590

申请日：1990-10-31

Applicant: TORAY INDUSTRIES

Inventor： NAKAI SAKIE ,  SATOU HARUYO

IPC: C07C209/88 ,  C07B57/00 ,  C07C211/11

Abstract: PURPOSE:To obtain the subject compound in good yield and high optical purity according to a simple method by optically resolving (RS)-1,2-propanediamine using optically active N-p-toluenesulfonylaspartic acid, etc., as a resolving agent. CONSTITUTION:(RS)-1,2-Propanediamine is brought into contact with optically active N-p-toluenesulfonylaspartic acid, N-benzenesulfonylaspartic acid or N- benzoylglutamic acid as a resolving agent in an amount of 0.1-2.0mol, preferably 0.3-1.0mol, etc., based on 1mol (RS)-propanediamine in a solvent such as water and, as necessary, in the coexistence of a mineral acid such as sulfuric acid or an organic acid such as acetic acid to carry out optical resolution. The resultant solution is subsequently cooled and/or concentrated to deposit crystals of sparingly soluble diastereomer salts. The deposited crystals are then readily separated by an ordinary solid-liquid separating method such as filtration or centrifugation. Thereby, the objective optically active compound useful as a synthetic raw material for medicines such as a carcinostatic agent is obtained.

公开(公告)号：JPH0413659A

公开(公告)日：1992-01-17

申请号：JP11448090

申请日：1990-04-28

Applicant: TORAY INDUSTRIES

Inventor： ITO NORIKO ,  SATOU HARUYO

IPC: C07D207/12 ,  C07B57/00

Abstract: PURPOSE:To obtain the subject optically active compound, simultaneously recover a resolving agent in an ultrahigh yield and reuse the aforementioned agent by carrying out optical resolution using (RS)-1-benzyl-3-hydroxypyrrolidine with a specific optically active carboxylic acid as the resolving agent. CONSTITUTION:(RS)-1-Benzyl-3-hydroxypyrrolidine is optically resolved with an optically active carboxylic acid (e.g. p-toluenesulfonyl-D-phenylglycine) expressed by the formula (R is benzenesulfonyl, toluenesulfonyl, benzoyl or toluoyl) as a resolving agent to afford optically active 1-benzyl-3- hydroxypyrrolidine. The optically active carboxylic acid, used as the resolving agent and expressed by the formula is sparingly soluble and can be recovered from a diastereomer salt solution in an ultrahigh yield. Since the optical purity is held by the above-mentioned resolving agent, optical resolution can be carried out by reuse thereof.

公开(公告)号：JPH03215451A

公开(公告)日：1991-09-20

申请号：JP1015490

申请日：1990-01-18

Applicant: TORAY INDUSTRIES

Inventor： MIYATA AKIRA ,  SATOU HARUYO

IPC: B01J31/04 ,  C07B55/00 ,  C07B61/00 ,  C07C51/353 ,  C07C59/48

Abstract: PURPOSE:To perform the title racemization by heating an optically active 2- hydroxy-4-phenylbutyric acid in the presence of acetic anhydride and a base to simply obtain the corresponding racemic modification in high efficiency. CONSTITUTION:An optically active 2-hydroxy-4-phenylbutyric acid is heated at pref. 50-150 deg.C in the presence of (1) pref. 1.0-3.0mol of acetic anhydride per mol of the compound and (2) pref. 0.05-2.0mol of a base (e.g. an alkali or alkaline earth metal salt of lower aliphatic or aromatic carboxylic acid or organic amine) per mol of the compound, thus accomplishing the objective racemization of the above optically active compound in an advantageous manner. With the present method, the above-mentioned optically active compound, one of such compounds, formed as a by-product in an optical resolution can be reused by racemization; therefore, this optically active compound useful as a raw material of various medicines (e.g. cilazapril as a hypotensive agent active as an angiotensinase inhibitor) can be produced in an industrially advantageous way.

公开(公告)号：JPH03112490A

公开(公告)日：1991-05-14

申请号：JP24883689

申请日：1989-09-25

Applicant: TORAY INDUSTRIES

Inventor： FUJIKAWA KAZUHIRO ,  SATOU HARUYO ,  YONEHARA TORU ,  MIYATA AKIRA

IPC: C12P13/22 ,  C12R1/01 ,  C12R1/06 ,  C12R1/13 ,  C12R1/15 ,  C12R1/19

Abstract: PURPOSE:To produce L-homophenylalanine useful as a raw material for a precursor of ACE inhibitor, having high optical purity, efficiently and inexpensively by treating benzylpyruvic acid with a culture mixture or cells of bacterium having specific action. CONSTITUTION:Benzylpyruvic acid (substrate concentration: about 0.1-5%) is treated with a culture mixture of a bacterium such as Corynebacterium glutamicum ATCC 13032 belonging to at least one of Corynebacterium, Brevibacterium, Bacillus, Microbacterium, Citrobacter, Arthrobacter and Escherichia, capable of converting benzylpyruvic acid into L-homophenylalanine or cells or treated material thereof at 20-40 deg.C, preferably 25-35 deg.C at pH7.5-9.0 and L-homophenylalanine is isolated from the reaction solution and collected.

公开(公告)号：JPH02306944A

公开(公告)日：1990-12-20

申请号：JP12823489

申请日：1989-05-22

Applicant: TORAY INDUSTRIES

Inventor： HASEGAWA SAKIE ,  SATOU HARUYO

IPC: C07C209/88 ,  C07C211/29

Abstract: PURPOSE:To easily obtain the subject compound having high optical purity and useful as an optical resolution agent for racemic acids, in high yield, by using an optically active N-acetyl-2-(p-methylphenyl)alanine as an optical resolution agent. CONSTITUTION:1Mol of (RS)-1-(p-bromophenyl)ethylamine is brought into contact with 0.1-2.0mol of optically active (D)- or (L)-N-acetyl-2-(p-methylphenyl)alanine as an optical resolution agent in a solvent (e.g. water or lower alcohol) at 0-80 deg.C to effect the optical resolution of the compound. The obtained solution is cooled and/or concentrated to crystallize scarcely soluble diastereomer salt and the crystal is easily separated by a solid-liquid separation process such as filtration to obtain the objective compound. The above resolution agent can be easily recovered by the treatment with an acid and alkali and the recovered optically active N-acetyl-2-(p-methylphenyl)alanine can be reused.

公开(公告)号：JPH01225499A

公开(公告)日：1989-09-08

申请号：JP5206788

申请日：1988-03-04

Applicant: TORAY INDUSTRIES

Inventor： MIYATA AKIRA ,  SATOU HARUYO

IPC: C12P41/00

Abstract: PURPOSE:To industrially and advantageously obtain the subject compound useful as a raw material for various medicines, such as hypotensive agent, etc., by reacting an ester of 2-hydroxy-4-phenylbutyric acid ester with an asymmetric hydrolase. CONSTITUTION:An ester of (RS)-2-hydroxy-4-phenylbutyric acid expressed by the formula (R is alkyl) is reacted with a hydrolase (preferably an enzyme derived from the genus Pseudomonas, Candida, Chromobacterium or Mucor, or porcine pancreas) for asymmetrically hydrolyzing the ester of the 2-hydroxy-4- phenylbutyric acid, preferably at 20-40 deg.C and pH5-8 to afford the aimed compound.