Synthesis 2013; 45(10): 1319-1324
DOI: 10.1055/s-0032-1318507
paper
© Georg Thieme Verlag Stuttgart · New York

Novel Synthesis of Butyl (S)-2-Hydroxybutanoate, the Key Intermediate of PPARα Agonist (R)-K-13675 from Butyl (2S,3R)-Epoxybutanoate and Butyl (S)-2,3-Epoxypropanoate

Takaaki Araki
Tokyo New Drug Research Laboratories, Pharmaceutical Division, Kowa Co., Ltd., 2-17-43, Noguchicho, Higashimurayama, Tokyo 189-0022, Japan   Fax: +81(42)3950312   Email: k-sibuya@kowa.co.jp
,
Minoru Koura
Tokyo New Drug Research Laboratories, Pharmaceutical Division, Kowa Co., Ltd., 2-17-43, Noguchicho, Higashimurayama, Tokyo 189-0022, Japan   Fax: +81(42)3950312   Email: k-sibuya@kowa.co.jp
,
Yukiyoshi Yamazaki
Tokyo New Drug Research Laboratories, Pharmaceutical Division, Kowa Co., Ltd., 2-17-43, Noguchicho, Higashimurayama, Tokyo 189-0022, Japan   Fax: +81(42)3950312   Email: k-sibuya@kowa.co.jp
,
Kimiyuki Shibuya*
Tokyo New Drug Research Laboratories, Pharmaceutical Division, Kowa Co., Ltd., 2-17-43, Noguchicho, Higashimurayama, Tokyo 189-0022, Japan   Fax: +81(42)3950312   Email: k-sibuya@kowa.co.jp
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Further Information

Publication History

Received: 08 February 2013

Accepted after revision: 06 March 2013

Publication Date:
03 April 2013 (online)


Abstract

Novel synthetic methods for the production of butyl (S)-2-hydroxybutanoate starting from butyl (2S,3R)-epoxybutanoate or butyl (S)-2,3-epoxypropanoate were established. The former method utilized the regioselective thiolysis of the epoxybutanoate mediated by scandium triflate and subsequent reductive cleavage of the thioether to give butyl (S)-2-hydroxybutanoate with stereochemical retention in quantitative yield. The latter method utilized one-step conversion by a combination of methylmagnesium bromide and copper catalyst in high yield.

 
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