Synthesis of N-methyl-N-[(1S)-1-[(3R)-pyrrolidin-3-yl]ethyl]amine.
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).
Fleck
Thomas J
TJ
Early Process Research and Development, Medicinal Chemistry Research, and Chemical Research and Development, Pfizer, Inc., Kalamazoo, Michigan 49001, USA.
McWhorter
William W
WW
DeKam
Richard N
RN
Pearlman
Bruce A
BA
D000478:Alkylation; D000588:Amines / Q000138:chemical synthesis*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D024841:Fluoroquinolones / Q000138:chemical synthesis*; D011758:Pyrroles / Q000138:chemical synthesis*; D011759:Pyrrolidines / Q000737:chemistry*; D015363:Quinolones / Q000138:chemical synthesis*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000588:Amines; D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D011758:Pyrroles; D011759:Pyrrolidines; D015363:Quinolones; C032519:pyrrolidine; C105016:premafloxacin