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Synthesis 2012(1): 51-56  
DOI: 10.1055/s-0031-1289619
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

New Procedure for the Preparation of (1R,2R)-2-[(R)-3-(Benzyloxy)pyr­rolidin-1-yl]cyclohexanol

Haiwei Ye, Chuanming Yu*, Weihui Zhong
Key Laboratory of Pharmaceutical Engineering of Ministry of Education, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, P. R. of China
Fax: +86(571)88320867; e-Mail: ycm@zjut.edu.cn;
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Publication History

Received 19 October 2011
Publication Date:
23 November 2011 (online)

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Abstract

A novel route to an intermediate of vernakalant, (1R,2R)-2-[(R)-3-(benzyloxy)pyrrolidin-1-yl]cyclohexanol from ethyl (R)-4-chloro-3-hydroxybutanoate is described. It was found that the key intermediate (R)-4-(benzyloxy)-1-[(1R,2R)-2-(tert-butyldimethylsiloxy)cyclohexyl]pyrrolidin-2-one could be isolated with high dia­stereomeric excess (up to 99% de) from its isomer by column chromatography alone, without further chemical resolution.

Key words

(1R,2R)-2-[(R)-3-(benzyloxy)pyrrolidin-1-yl]cyclohexanol - vernakalant - enantioselectivity

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