Kaneka Corporation

H. Lundbeck A/s

Toshihiro Takeda

Yasuyoshi Ueda

Kenji Inoue

Yoshihide Fuse

Koichi Kinoshita

Nobuo Nagashima

Kazumi Okuro

Akio Fujii

Hans Petersen

Akira Nishiyama

Tadashi Moroshima

Masaru Mitsuda

Koki Yamashita

Narumi Kishimoto

Hiroshi Murao

Masanobu Sugawara

Yasuhiro Saka

Masatoshi Ohnuki

Robert Dancer

Takashi Yoshida

Haleh Ahmadian

Hiroaki Yasukouchi

Takahisa Kato

Kohei Mori

Lars Ole Lyngso

Koji Machida

Shogo Yamamoto

Naoki Taoka

Makoto Funabashi

A tri-carbobenzoxy-arginine represented by the following formula (2): is produced by carbobenzoxylating the arginine or arginine derivative (1) represented by the following formula (1), or a salt thereof: by adding carbobenzoxy chloride and a base in a water/organic solvent bilayer system to an arginine or arginine derivative (1) represented by the formula (1), or a salt thereof.

Method for producing tri-carbobenzoxy-arginine

The present invention provides a process for producing a 3-aralkyloxypyrrolidine derivative which is important for production of pharmaceutical products and the like. In the present invention, a N-protected-3-hydroxypyrrolidine is converted into a N-protected-3-aralkyloxypyrrolidine by allowing an aralkyl halide to act in the presence of a base and at least one of a metal halide and a phase-transfer catalyst followed by deprotecting a N-protecting group to convert it to a 3-aralkyloxypyrrolidine derivative and subsequently treating the derivative in a solvent containing a polar solvent, thereby obtaining the 3-aralkyloxypyrrolidine derivative as a crystal. According to the present invention, a 3-aralkyloxypyrrolidine derivative of high purity can be produced conveniently and efficiently on an industrial scale.

Process for production of aralkyloxypyrrolidine derivative

Provided is a process for production of a &#x3b2;-amino-&#x3b1;-hydroxy carboxamide derivative that is important in production of drugs or the like. In the presence of a predetermined solvent, a &#x3b2;-(N-protected)amino-&#x3b1;-hydroxycarboxylic acid is reacted with an amine to conversion to a &#x3b2;-(N-protected)amino-&#x3b1;-hydroxy carboxamide derivative; then the derivative is deprotected for conversion to a &#x3b2;-amino-&#x3b1;-hydroxy carboxamide derivative; and the derivative is crystallized using a protic solvent to obtain a crystal. The high-purity &#x3b2;-amino-&#x3b1;-hydroxy carboxamide derivative can be stably produced on an industrial scale by the process.

Process for production of &#x3b2;-amino-&#x3b1;-hydroxy carboxamide derivative

The present invention relates to a novel method for the preparation of diol intermediates having the formula (II) and/or the opposite enantiomer of an acylated diol having the formula (IV) useful for the preparation of escitalopram involving selective enzymatic acylation or deacylation. 

Method for the separation of intermediates which may be used for the preparation of escitalopram

The invention provides processes for producing efficiently optically active 2-halogenocarboxylic acids useful in the preparation of drugs or the like and salts thereof with amines. Specifically, an optically active 2-halogenocarboxylic acid is produced by halogenating an optically active amino acid in water in the presence of a hydrophobic organic solvent and nitrous acid with the configuration retained and with the racemization inhibited through the removal of 2-hydroxy-bromocarboxylic acid formed as a by-product; the obtained optically active 2-halogenocarboxylic acid is transferred to an aqueous phase by converting it into a salt thereof with a base, followed by the removal of the organic phase; and the optically active 2-halogenocarboxylic acid is transferred again to an organic solvent phase, followed by the removal of the aqueous phase, whereby an optically active 2-halogenocarboxylic acid is obtained through the removal of a halogen component. Further, a high-quality salt of an optically active 2-halogenocarboxylic acid with an amine can be obtained by a crystallization method wherein the amine is added over the period of &#xbd; hour or longer either continuously or in portions and/or wherein the crystallization solvent consists of a hydrophobic organic solvent and a hydrophilic organic solvent.

Process for production of optically active 2-halogeno-carboxylic acids

The present invention provides a process of starting from N-alkoxycarbonyl-ethylamine compounds having a leaving group at the &#x3b2;-position to prepare oxazolidinone derivatives of &#x3b2;-hydroxyethylamine compounds having an inverted steric configuration at the &#x3b2;-position carbon, which comprises introducing a step of treating in contact with water with heating under acidic to neutral conditions into the process. Also, the present invention provides a process of starting from N-alkoxycarbonyl-ethylamine compounds having a leaving group at the &#x3b2;-position to prepare &#x3b2;-hydroxyethylamine compounds having an inverted steric configuration at the &#x3b2;-position carbon, which comprises subjecting the oxazolidinone derivatives prepared as described above to a step of treating in contact with water under basic conditions.

Processes for preparing oxazolidinone derivatives of &#x3b2;-hydroxyethlamine compounds and for preparing &#x3b2;-hydroxyethlamine compounds

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

The present invention provides a process for preparing 3-amino-2-hydroxypropionic acid derivatives (1) which does not use dangerous reagents, is economically advantageous, and is suitable for an industrial production, which process comprises: 

Process for producing 3-amino-2-hydroxypropionic acid derivatives

Process for preparing optically active amino acid derivatives

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Takasago, Japan

Toshihiro Takeda