Highly efficient synthesis of fibrinogen receptor antagonist L-734,217 via a novel chemoselective silyl-mediated conjugate addition of delta-lactams to 4-vinylpyridine

被引：18

作者：

Chung, JYL ^{[1
]}

Hughes, DL ^{[1
]}

Zhao, DL ^{[1
]}

Song, ZG ^{[1
]}

Mathre, DJ ^{[1
]}

Ho, GJ ^{[1
]}

McNamara, JM ^{[1
]}

Douglas, AW ^{[1
]}

Reamer, RA ^{[1
]}

Tsay, FR ^{[1
]}

Varsolona, R ^{[1
]}

McCauley, J ^{[1
]}

Grabowski, EJJ ^{[1
]}

Reider, PJ ^{[1
]}

机构：

[1] MERCK & CO INC,MERCK SHARP & DOHME RES LABS,DEPT ANALYT RES,RAHWAY,NJ 07065

来源：

JOURNAL OF ORGANIC CHEMISTRY | 1996年 / 61卷 / 01期

关键词：

D O I：

10.1021/jo951214f

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A highly practical chromatography-free six-step synthesis of L-734,217 suitable for large scale preparation is described. The key chiral pyridine acid intermediate (R)-1 was prepared in four steps based on a novel chemoselective silyl-mediated conjugate addition of ethyl (2-oxopiperidin-1-yl)acetate to 4-vinylpyridine and a highly productive, recyclable, kinetic resolution with quinine. Subsequent salt breaking/peptide coupling with benzyl 3-(R)-aminobutyrate (2) in a biphasic system, followed by concomitant hydrogenation of the pyridine ring and debenzylation afforded L-734,217 in 20% overall yield (30% with one recyle) from 2-piperidone. The mechanism of this key conjugate addition to 4-vinylpyridine was studied by C-13 NMR.

引用

页码：215 / 222

页数：8

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