405512-97-2

Upstream product

• 190269-75-1 methyl (1R,2R,3S)-2-(4-fluorophenyl)-3-hydroxycyclopentane-1-carboxylate 
• 190269-78-4 (1R,2R,3S)-2-(4-fluorophenyl)-3-hydroxycyclopentane-1-carboxylic acid 
• 18162-48-6 tert-butyldimethylsilyl chloride 
• 405512-96-1 (1S,2R,3R)-2-(4-fluorophenyl)-3-hydroxymethylcyclopentanol 

Downstream Products

• 912807-36-4 (R)-1-[(1R,2R,3S)-3-{(R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy}-2-(4-fluorophenyl)cyclopentylmethyl]piperidine-3-carboxylic acid tert-butyl ester 
• 405512-99-4 [(1R,2R,3S)-3-{1-(3,5-bis(trifluoromethyl)phenyl)vinyloxy}-2-(4-fluorophenyl)cyclopentylmethoxy]tert-butyldimethylsilane 
• 190266-45-6 [(1R,2R,3S)-3-{(R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy}-2-(4-fluorophenyl)cyclopentyl]methanol 
• 912807-20-6 3,5-bis(trifluoromethyl)benzoic acid (1S,2R,3R)-3-(tert-butyldimethylsilanyloxymethyl)-2-(4-fluorophenyl)cyclopentyl 

Relevant academic research and scientific papers

Stereoselective preparation of a cyclopentane-based NK1 receptor antagonist bearing an unsymmetrically substituted sec-sec ether

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.