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

被引：20

作者：

Singer, Robert A. ^{[1
]}

Ragan, John A. ^{[1
]}

Bowles, Paul ^{[1
]}

Chisowa, Esmort ^{[1
]}

Conway, Brian G. ^{[1
]}

Cordi, Eric M. ^{[1
]}

Leeman, Kyle R. ^{[2
]}

Letendre, Leo J. ^{[1
]}

Sieser, Janice E. ^{[1
]}

Sluggett, Gregory W. ^{[2
]}

Stanchina, Corey L. ^{[1
]}

Strohmeyer, Holly ^{[2
]}

Blunt, Jon ^{[3
]}

Taylor, Stuart ^{[3
]}

Byrne, Ciaran ^{[4
]}

Lynch, Denis ^{[4
]}

Mullane, Sandra ^{[4
]}

O'Sullivan, Maria M. ^{[4
]}

Whelan, Marcella ^{[4
]}

机构：

[1] Pfizer Worldwide Res & Dev, Chem Res & Dev, Groton, CT 06340 USA

[2] Pfizer Worldwide Res & Dev, Analyt Res & Dev, Groton, CT 06340 USA

[3] Pfizer Proc Dev Facil, Chem Res & Dev, Sandwich, Kent, England

[4] Pfizer Global Supply, Ringaskiddy, Cork, Ireland

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2014年 / 18卷 / 01期

关键词：

HEPATITIS-C; LITHIUM DIISOPROPYLAMIDE; ACYLATION REACTIONS; ALDOL REACTION; THERAPY;

D O I：

10.1021/op4002356

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

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 etiolate and ketone electrophile). A sequence consisting of Sonogashira coupling, acylation and hydrogenation delivered acetate 24, and Dieckmann cyclization provided beta-keto lactone 2.

引用

页码：26 / 35

页数：10

共 1 条

[1] Synthesis of Filibuvir. Part II. Second-Generation Synthesis of a 6,6-Disubstituted 2H-Pyranone via Dieckmann Cyclization of a β-Acetoxy Ester
Peng, Zhihui
Ragan, John A.
Colon-Cruz, Roberto
Conway, Brian G.
Cordi, Eric M.
Leeman, Kyle
Letendre, Leo J.
Ping, Li-Jen
Sieser, Janice E.
Singer, Robert A.
Sluggett, Gregory W.
Strohmeyer, Holly
Vanderplas, Brian C.
Blunt, Jon
Mawby, Nicola
Meldrum, Kevin
Taylor, Stuart
ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2014, 18 (01) : 36 - 44

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