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Published on: June 23, 2019
Synthesis of N-methyl-N-[(1S)-1-[(3R)-pyrrolidin-3-yl]ethyl]amine
Thomas J Fleck1, William W McWhorter, Richard N DeKam
1Early Process Research and Development, Medicinal Chemistry Research, and Chemical Research and Development, Pfizer, Inc., Kalamazoo, Michigan 49001, USA.
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).
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