Enantioselective synthesis of (S)- and (R)-fluoxetine hydrochloride

被引：37

作者：

Miles, WH ^{[1
]}

Fialcowitz, EJ ^{[1
]}

Halstead, ES ^{[1
]}

机构：

[1] Lafayette Coll, Dept Chem, Easton, PA 18042 USA

来源：

TETRAHEDRON | 2001年 / 57卷 / 50期

关键词：

ene reactions; furans; asymmetric synthesis;

D O I：

10.1016/S0040-4020(01)01012-2

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The enantioselective synthesis of fluoxetine hydrochloride, a potent serotonin-uptake inhibitor, is described. The synthesis of (S)-fluoxetine hydrochloride begins with the asymmetric carbonyl-ene reaction of benzaldehyde with 3-methylene-2,3-dihydrofuran (1) catalyzed by Ti[OCH(CH3)(2)](4)/(S)-BINOL to give (S)-2-(3-furyl)-1-phenyl-1-ethanol (2) in 90% yield and 95% ee. In five steps, alcohol 2 was converted into (S)-fluoxetine hydrochloride (97% ee and 56% overall yield from benzaldehyde). (R)-fluoxetine hydrochloride was prepared by the same sequence except that Ti[OCH(CH3)(2)](4)/(R)-BINOL was used in the first reaction to give the enantiomer of 2. (C) 2001 Elsevier Science Ltd. All rights reserved.

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页码：9925 / 9929

页数：5

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