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Synthese und absolute Konfiguration von Clemastin und seiner Isomeren
Author(s) -
Ebnöther Anton,
Weber HansPeter
Publication year - 1976
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19760590721
Subject(s) - chemistry , methiodide , absolute configuration , stereochemistry , medicinal chemistry
Synthesis and Absolute Configuration of Clemastine and its Isomers. Condensation of 4‐chloro‐α‐methylbenzhydrylalkohol ( 1 ) with 2‐(2‐chloroethyl)‐1‐methylpyrrolidine ( 2 ) gave an isomeric mixture of 2‐[2‐( p ‐chloro‐α‐methyl‐=‐phenylbenzyloxy)ethyl]‐1‐methylpyrrolidine ( 3 ) and 4‐( p ‐chloro‐=‐phenylbenzyloxy)‐1‐methyl‐hexahydroazepin ( 4 ). The separation of the four possible optically active isomers of 3 is described and their absolute configuration established by degradation to ( R )‐ and ( S )‐1‐methyl‐2‐pyrrolidineethanol ( 6 ), respectively, and by an X‐ray cristallographic analysis of the quarternary methiodide of the isomer 3‐A . Clemastine ( 3‐A ) is (+)‐( 2R )‐2‐[2‐((α R )‐( p ‐chloro‐α‐methyl‐α‐phenylbenzyloxy)ethyl)]‐1‐methylpyrrolidine.