Stereocontrolled preparation of a nonpeptidal (-)-spirobicyclic NK-1 receptor antagonist

被引：36
|
作者：
Maligres, PE
Waters, MM
Lee, J
Reamer, RA
Askin, D
Ashwood, MS
Cameron, M
机构：
[1] Merck & Co Inc, Merck Res Labs, Dept Proc Res, Rahway, NJ 07065 USA
[2] Merck & Co Inc, Merck Sharp & Dohme Res Labs, Dept Proc Res, Hoddesdon EN11 9BU, Herts, England
来源：
JOURNAL OF ORGANIC CHEMISTRY | 2002年 / 67卷 / 04期
关键词：
D O I：
10.1021/jo0157472
中图分类号：
O62 [有机化学];
学科分类号：
070303 ; 081704 ;
摘要：
The synthesis of a spirobicyclic NK-1 receptor (Substance-P) antagonist I antipode is described. Retrosynthetic analysis reveals an allylic halide A bearing the cyclopropoxy-substituted aryl group and a 2-phenyl-3-piperidone B. The stereochemistry in the spirobicyclic system bearing three chiral centers is initially set via a highly diastereoselective zinc-mediated coupling of the allylic bromide 23 to the optically active ketopiperidine 3. The remaining benzylic asymmetric center is set by a diastereoselective hydroboration followed by cyclization to the spirobicyclic system.
引用
收藏
页码：1093 / 1101
页数：9
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