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Updated: Mar 25, 2026

Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles
Published on: August 22, 2018
Two Scalable Syntheses of (S)-2-Methylazetidine
Matthew S Dowling1, Dilinie P Fernando1, Jie Hou2
1Pfizer Worldwide Research & Development, Eastern Point Road, Groton, Connecticut 06340, United States.
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.
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