Development of an efficient and stereoselective manufacturing route to idoxifene

被引：15

作者：

Ace, KW ^{[1
]}

Armitage, MA ^{[1
]}

Bellingham, RK ^{[1
]}

Blackler, PD ^{[1
]}

Ennis, DS ^{[1
]}

Hussain, N ^{[1
]}

Lathbury, DC ^{[1
]}

Morgan, DO ^{[1
]}

O'Connor, N ^{[1
]}

Oakes, GH ^{[1
]}

Passey, SC ^{[1
]}

Powling, LC ^{[1
]}

机构：

[1] GlaxoSmithKline Pharmaceut, Chem Dev, Tonbridge TN11 9AN, Kent, England

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2001年 / 5卷 / 05期

关键词：

D O I：

10.1021/op0100394

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

A literature route to 1-(2-{4-[(E)-1-(4-iodophenyl)-2-phenyl-but-1-enyl]phenoxy}ethyl)pyrrolidine (idoxifene) has been modified to tackle various scale-up issues and provide initial supplies. A new highly efficient, robust, and stereoselective manufacturing route is described in detail. This route involves diastereoselective synthesis of tertiary alcohol (1RS,2SR)-1-(4-iodophenyl)-2-phenyl-1-[4-(2-pyrrolidin-1-yl-ethoxy)phenyl]butan-1-ol by Grignard addition to the ketone 1-(4-iodophenyl)-2-phenyl-1-butanone followed by derivatisation and stereoselective syn elimination to provide idoxifene in excellent yield and geometric purity. Evaluation of a more direct route to idoxifene using a McMurry low-valent titanium coupling reaction is also described.

引用

页码：479 / 490

页数：12

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