Synthesis 2017; 49(02): 424-428
DOI: 10.1055/s-2016-0036-1588899
paper
© Georg Thieme Verlag Stuttgart · New York

Multistep Continuous-Flow Synthesis of (–)-Oseltamivir

Shin Ogasawara, Yujiro Hayashi*
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Publication History

Received: 23 August 2016

Accepted after revision: 29 September 2016

Publication Date:
03 November 2016 (eFirst)

Dedicated to Professor Dieter Enders on the occasion of his 70th birthday

Abstract

A continuous-flow synthesis of (–)-oseltamivir composed of five flow units was accomplished. In each unit, the following reactions proceed efficiently: (1) a diphenylprolinol silyl ether mediated Michael reaction, (2) a domino reaction of Michael and intermolecular Horner–Wadsworth–Emmons reactions, (3) protonation, (4) epimerization, and (5) reduction of a nitro group to an amine. (–)-Oseltamivir was obtained in 13% total yield through a single flow with a residence time of 310 minutes.

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