Synthesis 2015; 47(05): 712-720
DOI: 10.1055/s-0034-1379641
© Georg Thieme Verlag Stuttgart · New York

A Concise and Efficient Synthesis of Substituted Morpholines

Sundeep Dugara, Amit Sharmab, Bilash Kuilab, Dinesh Mahajan*b, Sandeep Dwivedib, Vinayak Tripathib
  • aSphaera Pharma Pte. Ltd., 8 Temasek Boulevard, #22-03 Suntec Tower, 038988, Singapore
  • bSphaera Pharma Pvt. Ltd., Plot No 32, Sector 5, IMT Manesar 122051, India   Email:
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Publication History

Received: 19 September 2014

Accepted after revision: 17 November 2014

Publication Date:
23 December 2014 (eFirst)


A simple and efficient method has been developed for the synthesis of substituted morpholines by a sequence of coupling, cyclization, and reduction reactions of easily available amino alcohols and α-halo acid chlorides. Various mono-, di-, and trisubstituted morpholines, spiro morpholines, and ring-fused morpholines, as well as morpholine homologues, were synthesized in good to excellent yields by a single methodology under similar reaction conditions. The method was also used in a multigram synthesis of (3S)-3-methylmorpholine.

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