Kaneka Corporation

Pfizer Corporation

Kanegafuchi Kagaku Kogyo Kabushiki Kaisha

Nobuo Nagashima

Tatsuya Honda

Akira Nishiyama

Masanobu Sugawara

Yasuhiro Saka

Kenji Inoue

Yasuyoshi Ueda

Tadashi Moroshima

Yoshihide Fuse

Koichi Kinoshita

Naoaki Taoka

Kazumi Okuro

Toshihiro Takeda

Akio Fujii

Narumi Kishimoto

Kohei Mori

Yoshihiko Yasohara

Junzo Hasegawa

Takehisa Ohashi

Noboru Ueyama

Kazunori Kan

Hirokazu Nanba

Yoshifumi Yanagida

Satohiro Yanagisawa

Takahiro Ohishi

Masashi Izumida

Daisuke Moriyama

Masahiko Yamada

Tatsuyoshi Tanaka

Hirofumi Maeda

Hiroshi Murakami

The present invention provides a simple industrial process for producing an L- or D-optically active &#x3b1;-methylcysteine derivative or its salt, which is a useful pharmaceutical intermediate, from readily available, inexpensive raw materials. In a process for producing an L- or D-optically active &#x3b1;-methylcysteine derivative or its salt, a racemic N-carbamoyl-&#x3b1;-methylcysteine derivative or its salt is D-selectively cyclized with hydantoinase to produce a D-5-methyl-5-thiomethylhydantoin derivative or its salt and an N-carbamoyl-&#x3b1;-methyl-L-cysteine derivative or its salt, which are then subjected to deprotection of the amino group and the sulfur atom, and hydrolysis.

Process for producing optically active &#x3b1;-methylcysteine derivative

An objective of the present application is to provide an industrially practicable method for producing an optically-active 3-amino-2-hydroxypropionic cyclopropylamide derivative or salt thereof from an inexpensive easily-available starting material. The derivative or salt thereof is useful as an intermediate for a medicine. It is also intended by the present application to provide a useful intermediate of the derivative. The objective is attained by the following method. First, an easily-available 2-halo-3-oxopropionic acid derivative is asymmetrically reduced, and then epoxidated to produce an optically-active epoxycarboxylic acid derivative. Next, the derivative is converted into an optically-active epoxyamide derivative by reaction with cyclopropylamine, and then reacted with a nitrile to obtain an optically-active oxazolinamide derivative. Subsequently, selective acid solvolysis of the oxazoline skeleton gives the optically-active 3-amino-2-hydroxypropionic cyclopropylamide derivative or salt thereof.

Process for production of optically active-3-amino-2-hydroxypropionic cyclopropylamide derivatives and salts thereof

The present invention relates to a process for producing an optically active 1,4-pentanediol by asymmetrically reducing 5-hydroxy-2-pentanone, which is easily available at low cost. The present invention also relates to a process for producing an optically active 1-substituted 2-methylpyrrolidine including sulfonylating the optically active 1,4-pentanediol to convert it to an optically active sulfonate compound, and reacting the compound with an amine. According to the processes of the present invention, an optically active 1,4-pentanediol and an optically active 1-substituted 2-methylpyrrolidine, which are useful as an intermediate for medicines and an intermediate for agricultural chemicals, can be simply produced from an inexpensive starting material.

Processes for producing optically active 1-substituted 2-methylpyrrolidine

A process for easily producing an optically active &#x3b2;-amino alcohol useful as a pharmaceutical intermediate from an inexpensive, readily available starting material is provided. A readily available &#x3b1;-substituted ketone is reacted with an optically active amine to yield a diastereomer mixture of an optically active &#x3b1;-substituted aminoketone. One of the diastereomers is isolated optionally after the diastereomers are converted to salts with an acid. The optically active &#x3b1;-substituted aminoketone or a salt thereof thus isolated was stereoselectively reduced to yield an optically active &#x3b2;-substituted amino alcohol. The optically active &#x3b2;-substituted amino alcohol is subjected to hydrogenolysis to produce an optically active &#x3b2;-amino alcohol or a salt thereof.

Process for producing optically active &#x3b2;-amino alcohol

An optically active N-protected azetidine-2-carboxylic acid (5) can be produced by preparing an optically active 4-amino-2-halobutyric acid (3) 

Process for producing optically active azetidine-2-carboxylic acids

The present invention provides a method for easily producing an (R)-3-[4-(trifluoromethyl)phenylamino]-pentanoic acid amide derivative useful for an intermediate for pharmaceutical products, particularly an inhibitor of a cholesteryl ester transfer protein (CETP) from easily available raw materials. In the present invention, (S)-N-[4-(trifluoromethyl)phenyl]-3-hydroxypentanoic acid amide prepared from easily available raw materials leads a production of (R)-4-ethyl-1-[4-(trifluoromethyl)phenyl]-2-azetidinone to give (R)-3-[4-(trifluoromethyl)phenylamino]-pentanoic acid amide. Furthermore, (R)-4-ethyl-1-[4-(trifluoromethyl)phenyl]-2-azetidinone is reacted with a carbamic acid ester to give an (R)-3-[4-(trifluoromethyl)phenylamino]-pentanoic acid amide derivative.

Method for producing (R)-3-[4-(trifluoromethyl) phenylamino]-pentanoic acid amide derivative

An optically active amino acid derivative is produced by N-protecting an optically active 3-haloalanine derivative followed by cyclization, or cyclizing this derivative followed by N-protection to thereby give an optically active N-protected-aziridine-2-carboxylic acid derivative which is protected by a benzenesulfonyl group substituted by nitro at the 2- and/or 4-positions and then treating this product with an organic metal reagent, or by N-protecting an optically active 3-haloalanine derivative to thereby give N-protected-aziridine-2-carboxylic acid which is protected by a benzenesulfonyl group substituted by nitro at the 2- and/or 4-positions and then treating this product with an organic metal reagent. According to this process, natural and unnatural optically active amino acids can be produced from inexpensive materials by using simple procedures.

Process for producing optically active amino acid derivatives

An optically active N-protected azetidine-2-carboxylic acid (5) can be produced by preparing an optically active 4-amino-2-halobutyric acid (3)

Process for cyclizing optically active 4-amino-2-halogenobutyric acids

Process for preparing optically active amino acid derivatives

Process for preparation of optically active N-substituted azetidine-2-carboxylic acids

A 2- or 4-nitrobenzenesulfonamide is allowed to react with an alkali metal alkoxide to remove a nitrobenzenesulfonyl group to thereby obtain an amine corresponding to the amide. Furthermore, a method for producing an amine derivative by allowing the resulting amine without isolation to react with an activated, substituted oxycarbonyl compound or an activated acyl compound is provided. According to this method, a corresponding free amine and its substituted derivative can be produced easily and industrially advantageously from the 2- or 4-nitrobenzenesulfonamide without using a thiol compound.

Process for the removal of nitrobenzenesulfonyl

Process for the preparation of 3-hydroxytetrahydrofuran

.gamma.-oxo-homophenylalanine derivatives and process for producing

Process for preparing an enol silyl ether compound

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Takasago, Japan

Nobuo Nagashima