N-甲基-N-[(1S)-1-[(3R)-吡咯烷-3-基]乙基]胺的合成。

Synthesis of N-methyl-N-[(1S)-1-[(3R)-pyrrolidin-3-yl]ethyl]amine.

作者信息

Fleck Thomas J, McWhorter William W, DeKam Richard N, Pearlman Bruce A

机构信息

Early Process Research and Development, Medicinal Chemistry Research, and Chemical Research and Development, Pfizer, Inc., Kalamazoo, Michigan 49001, USA.

出版信息

J Org Chem. 2003 Dec 12;68(25):9612-7. doi: 10.1021/jo0349633.

DOI:10.1021/jo0349633

PMID:14656085

Abstract

N-Methyl-N-[(1S)-1-[(3R)-pyrrolidin-3-yl]ethyl]amine (1)(1) is a key intermediate in the preparation of premafloxacin (2), which was under development as an antibiotic for use against pathogens of veterinary importance. This paper describes the development of a practical, efficient, and stereoselective process for the preparation of 1 from isobutyl (3S)-3-[methyl[(1S)-1-phenylethyl]amino]butanoate (5c). The key steps in the synthetic sequence are an asymmetric Michael addition, which yields 5c, and a stereoselective alkylation, which yields (3S,4S)-3-allyl-1,4-dimethylazetidin-2-one (17).

摘要

N-甲基-N-[(1S)-1-[(3R)-吡咯烷-3-基]乙基]胺(1)是制备普马沙星(2)的关键中间体，普马沙星作为一种抗生素正在研发中，用于对抗具有兽医重要性的病原体。本文描述了一种从(3S)-3-[甲基[(1S)-1-苯乙基]氨基]丁酸异丁酯(5c)制备1的实用、高效且立体选择性的方法。合成序列中的关键步骤是生成5c的不对称迈克尔加成反应以及生成(3S,4S)-3-烯丙基-1,4-二甲基氮杂环丁烷-2-酮(17)的立体选择性烷基化反应。