ASYMMETRIC-SYNTHESIS OF MK-0499

被引：138

作者：

TSCHAEN, DM

ABRAMSON, L

CAI, DW

DESMOND, R

DOLLING, UH

FREY, L

KARADY, S

SHI, YJ

VERHOEVEN, TR

机构：

[1] Department of Process Research, Merck Research Laboratories, Division of Merck & Co., Inc, Rahway, New Jersey 07065-0900

来源：

JOURNAL OF ORGANIC CHEMISTRY | 1995年 / 60卷 / 14期

关键词：

D O I：

10.1021/jo00119a008

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Described herein is an efficient asymmetric synthesis of the potent antiarrhthymia agent MK-0499. The route is convergent and is highlighted by two stereoselective reactions. A ruthenium-catalyzed, enantioselective hydrogenation of an enamide was developed for the preparation of the key amine intermediate. Oxazaborolidine-mediated ketone reduction was utilized to establish the alcohol stereochemistry. Optimization of this chemistry led to an IPA modified reduction method which provides enhanced stereoselectivity.

引用

页码：4324 / 4330

页数：7

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