title: Two Scalable Syntheses of (S)-2-Methylazetidine.
abstract: Two orthogonal routes for preparing (S)-2-methylazetidine as a bench stable, crystalline (R)-(-)-CSA salt are presented. One route features the in situ generation and cyclization of a 1,3-bis-triflate to form the azetidine ring, while the second route involves chemoselective reduction of N-Boc azetidine-2-carboxylic acid. Both sequences afford the desired product in good overall yields (61% and 49%) and high enantiomeric excess (>99% ee), avoid column chromatography, and are suitable for the large-scale production of this material.
authors.affiliation: Pfizer Worldwide Research & Development, Eastern Point Road, Groton, Connecticut 06340, United States.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Dowling
authors.affiliation: Pfizer Worldwide Research & Development, Eastern Point Road, Groton, Connecticut 06340, United States.
authors.forename: Dilinie P
authors.initials: DP
authors.lastname: Fernando
authors.affiliation: WuXi AppTec, 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Hou
authors.affiliation: WuXi AppTec, 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Pfizer Worldwide Research & Development, Eastern Point Road, Groton, Connecticut 06340, United States.
authors.forename: Aaron C
authors.initials: AC
authors.lastname: Smith