Efficient Synthesis of (2S,3S)-2-Ethyl-3-methylvaleramide Using (1S,2S)-Pseudoephedrine as a Chiral Auxiliary

被引：15

作者：

Li, Bin-Feng ^{[1
]}

Hughes, Robert M. ^{[1
]}

Le, Jackie ^{[1
]}

McGee, Kevin ^{[1
]}

Gallagher, Donald J. ^{[1
]}

Gross, Raymond S. ^{[1
]}

Provencal, David ^{[1
]}

Reddy, Jayachandra P. ^{[1
]}

Wang, Peng ^{[1
]}

Zegelman, Lev ^{[1
]}

Zhao, Yuxin ^{[1
]}

Zook, Scott E. ^{[1
]}

机构：

[1] Neurocrine Biosci Inc, San Diego, CA 92130 USA

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2009年 / 13卷 / 03期

关键词：

ASYMMETRIC-SYNTHESIS; PSEUDOEPHEDRINE; VALNOCTAMIDE;

D O I：

10.1021/op800260j

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

An efficient and scaleable synthesis of (2S,3S)-2-ethyl-3-methylvaleramide (1) has been developed starting from inexpensive and readily available L-isoleucine. The key step in this process is an asymmetric alkylation using (1S,2S)-pseudoephedrine as a chiral auxiliary. A practical procedure was developed to remove the sterically hindered pseudoephedrine auxiliary from the amide. The process consists of eight chemical steps and five isolations without any chromatographic purification. It has been successfully implemented to prepare several multikilogram batches of the target compound 1 in 41% overall yield.

引用

页码：463 / 467

页数：5

共 9 条

[1] Stereoselective pharmacokinetic analysis of valnoctamide in healthy subjects and in patients with epilepsy [J].