New technical synthesis of ethyl (R)-2-hydroxy-4-phenylbutyrate of high enantiomeric purity

被引：73

作者：

Herold, P ^{[1
]}

Indolese, AF ^{[1
]}

Studer, M ^{[1
]}

Jalett, HP ^{[1
]}

Siegrist, U ^{[1
]}

Blaser, HU ^{[1
]}

机构：

[1] Solvias AG, CH-4002 Basel, Switzerland

来源：

TETRAHEDRON | 2000年 / 56卷 / 35期

关键词：

HPB ester synthesis; enantioselective hydrogenation; cinchona modified platinum catalysts; ACE inhibitor; chiral intermediate; technical synthesis;

D O I：

10.1016/S0040-4020(00)00617-7

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A new technical synthesis to produce ethyl (R)-2-hydroxy-4-phenylbutyrate (5), an important intermediate for several ACE inhibitors with >99% ee in an over-all yield of 50-60% is described starting from acetophenone and diethyl oxalate. Key step is the chemo- and enantioselective hydrogenation of ethyl 2,4-dioxo-4-phenylbutyrate (6) (ee up to 86%) catalyzed by a heterogeneous Pt catalyst modified with dihydrocinchonidine, followed by crystallization of the 2-hydroxy-4-oxo ester 7 and hydrogenolysis of the 4-keto group. (C) 2000 Elsevier Science Ltd. All rights reserved.

引用

页码：6497 / 6499

页数：3

共 11 条

[1] THE DESIGN AND SYNTHESIS OF THE ANGIOTENSIN CONVERTING-ENZYME-INHIBITOR CILAZAPRIL AND RELATED BICYCLIC COMPOUNDS [J].