912807-36-4Relevant articles and documents
Stereoselective preparation of a cyclopentane-based NK1 receptor antagonist bearing an unsymmetrically substituted sec-sec ether
Kuethe, Jeffrey T.,Marcoux, Jean-Francois,Wong, Audrey,Wu, Jimmy,Hillier, Michael C.,Dormer, Peter G.,Davies, Ian W.,Hughes, David L.
, p. 7378 - 7390 (2007/10/03)
A highly efficient synthesis of the potent and selective NK-1 receptor antagonist 1 is described. The key transformation involved the etherification reaction between cyclopentanol 12 and chiral imidate 30 which was catalyzed by HBF4 to initially give ether 14 as a 17:1 mixture of diastereomers and in 75% combined yield. The diastereoselectivity was upgraded to 109:1 by crystallization of the triethylamine solvate 44 which was isolated in 54% yield from 12. Mechanistic studies confirmed that the etherification reaction proceeds through an unprecedented SN2 reaction pathway under typical S N1 reaction conditions.