Synthesis of (2R)-1-(4-Chloro-2-pyridyl)-2-(2-pyridyl)ethylamine: A Selective Oxime Reduction and Crystallization-Induced Asymmetric Transformation

Shigeto Negi; Masayuki Matsukura; Masanori Mizuno; Kazutoshi Miyake; Norio Minami

doi:10.1055/s-1996-4325

Synthesis 1996; 1996(8): 991-996
DOI: 10.1055/s-1996-4325

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Synthesis of (2R)-1-(4-Chloro-2-pyridyl)-2-(2-pyridyl)ethylamine: A Selective Oxime Reduction and Crystallization-Induced Asymmetric Transformation

Shigeto Negi^* , Masayuki Matsukura, Masanori Mizuno, Kazutoshi Miyake, Norio Minami

^*Eisai Co., Ltd., Tsukuba Research Laboratories, 1-3 Tokodai 5 chome, Tsukuba-shi, Ibaraki 300-26, Japan, Fax +81(298)472037

Abstract

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Reduction of 1-(4-chloro-2-pyridyl)-2-(2-pyridyl)ethanone oxime (3) using zinc in trifluoroacetic acid gave the corresponding racemic pyridylethylamine 4 in excellent yield without reductive removal of the chlorine atom. A subsequent diastereomeric crystallization of the amine 4 with an optically active cis-cyclohexanecarboxylic acid derivative in the presence of a catalytic amount of 3,5-dichlorosalicylaldehyde was found to give the desired R-amine 6 in 42% yield via a ”crystallization-induced asymmetric transformation”.

zinc-trifluoroacetic acid reduction - oxime reduction - isomerization-crystallization - optical resolution - chiral (4-chloropyridyl)methylamine

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