Synthesis of Filibuvir. Part II. Second-Generation Synthesis of a 6,6-Disubstituted 2H-Pyranone via Dieckmann Cyclization of a β-Acetoxy Ester
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- 作者：Zhihui Peng ; John A. Ragan ; Roberto Colon-Cruz ; Brian G. Conway ; Eric M. Cordi ; Kyle Leeman ; Leo J. Letendre ; Li-Jen Ping ; Janice E. Sieser ; Robert A. Singer ; Gregory W. Sluggett ; Holly Strohmeyer ; Brian C. Vanderplas ; Jon Blunt ; Nicola Mawby ; Kevin Meldrum ; Stuart Taylor
- 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：36-44
- 全文大小：427K
- ISSN：1520-586X
文摘
This paper describes an improved sequence for the conversion of an oxazolidinone (3) to a 尾-keto lactone (5). The primary drivers behind this change were the modest and variable yields observed in the intramolecular cyclization to generate the 尾-keto lactone. Changing the cyclization substrate from oxazolidinone to alkyl ester offered a significantly improved cyclization, as well as improvements in the alkyne hydrogenation. Selection of the optimal substrates for methanolysis and intermediate salt formation are also described.