Asymmetric synthesis of H1 receptor antagonist (R,R)-clemastine
Authors:
- 29 July 2015
- journal article
- research article
- Published by Springer Nature in Archives of Pharmacal Research
- Vol. 38 (12) , 2131-2136
Abstract
The first asymmetric synthesis of (R,R)-clemastine (1) has been accomplished by the coupling of (R)-tertiary alcohol 2 and (R)-chloroethylpyrrolidine 3 via O-alkylation. (R)-Tertiary alcohol 2 was synthesized by stereoselective alkylation of chiral α-benzyloxy ketone with Grignard reagent via chelation-controlled 1,4-asymmetric induction. In the reaction, chiral benzyl group acts as a chiral auxiliary as well as a protecting group. (R)-Chloroethylpyrrolidine 3 was prepared by asymmetric transformation starting with l-homoserine lactone, in which racemization-minimized N-allylation and ring-closing metathesis were involved as key steps.Keywords
Funding Information
- Sookmyung Women’s University Research Grants 2012
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