Synthesis of Filibuvir. Part I. Diastereoselective Preparation of a β-Hydroxy Alkynyl Oxazolidinone and Conversion to a 6,6-Disubstituted 2H-Pyranone

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• 作者：Robert A. Singer ; John A. Ragan ; Paul Bowles ; Esmort Chisowa ; Brian G. Conway ; Eric M. Cordi ; Kyle R. Leeman ; Leo J. Letendre ; Janice E. Sieser ; Gregory W. Sluggett ; Corey L. Stanchina ; Holly Strohmeyer ; Jon Blunt ; Stuart Taylor ; Ciaran Byrne ; Denis Lynch ; Sandra Mullane ; Maria M. O’Sullivan ; Marcella Whelan
• 刊名：Organic Process Research & Development
• 出版年：2014
• 出版时间：January 17, 2014
• 年：2014
• 卷：18
• 期：1
• 页码：26-35
• 全文大小：406K
• ISSN：1520-586X

文摘

This is the first in a series of three papers describing the identification and development of a commercial synthesis of filibuvir (1). This contribution describes development of an Evans aldol reaction to control the tertiary alcohol stereocenter, a challenging variant of that strategy in that both reacting partners were nonstandard (acetate enolate and ketone electrophile). A sequence consisting of Sonogashira coupling, acylation and hydrogenation delivered acetate 24, and Dieckmann cyclization provided 尾-keto lactone 2.