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AN ALTERNATE SYNTHESIS OF THE POTENT ANTIMUSCARINIC AGENT SILA-BIPERIDEN

 

作者: Jerzy Pikies,   Ludger Ernst,  

 

期刊: Phosphorus, Sulfur, and Silicon and the Related Elements  (Taylor Available online 1997)
卷期: Volume 128, issue 1  

页码: 179-190

 

ISSN:1042-6507

 

年代: 1997

 

DOI:10.1080/10426509708031573

 

出版商: Taylor & Francis Group

 

关键词: Sila-pharmaca;Hydrosilylation;Elimination of hydrogen bromide;thermally and baseinduced

 

数据来源: Taylor

 

摘要:

Sila-biperiden,9x(RS,SR), i. e. racemic (SiRS, C2SR)-(exo-bicyclo[2.2.1]hept-5-en-2-yl)phenyl(2-piperidinoethyl)silanol, the silicon analogue of the antimuscarinic agent biperiden, is prepared by a seven-step synthesis. The first step consists in the hydrosilylation of 5-exo-bromobicyclo[2.2.1]-hept-2-ene (2) with dichloro(phenyl)silane (1) in the presence of H2PtCl6. The product of the last synthetic step is a mixture of fourendo-(9n) and fourexo-diastereomers (9x) of (bicyclo[2.2.1]hept-5-en-2-yl)phenyl(2-piperidinoethyl)silanol and of the (tricyclo[2.2.1.02,6]hept-1−yl)silanol derivative9t. Eight-fold crystallization of the9n/9x/9t-mixture gave pure sila-biperiden (racemate) in an overall yield of 5.3%, which represents a more than 30-fold improvement over the earlier synthesis.

 

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