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Dynamic Kinetic Resolution of 2,3‐Dihydrobenzo[ b ]furans: Chemoenzymatic Synthesis of Analgesic Agent BRL 37959
Author(s) -
Bongen Patrick,
Pietruszka Jörg,
Simon Robert Christian
Publication year - 2012
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201200683
Subject(s) - chemistry , acylation , kinetic resolution , carboxylic acid , furan , saponification , enantiomer , stereochemistry , organic chemistry , medicinal chemistry , enantioselective synthesis , catalysis
An efficient asymmetric synthesis of ( S )‐2,3‐dihydrobenzo[ b ]furan‐3‐carboxylic acid ( 8 a ) and ( S )‐5‐chloro‐2,3‐dihydrobenzo[ b ]furan‐3‐carboxylic acid ( 8 b ) was established. Key to the success was the highly stereoselective enzymatic kinetic resolution of the corresponding methyl or ethyl esters that was further developed into a dynamic process. As a reliable and fast tool for analysing the enantiomeric excess, HPLC coupled with a CD detector was utilized. The route was completed by a Friedel–Crafts acylation of ethyl ( S )‐5‐chloro‐2,3‐dihydrobenzo[ b ]furan‐3‐carboxylate ( 7 c ) followed by saponification leading to ( S )‐5‐chloro‐2,3‐dihydrobenzo[ b ]furan‐3‐carboxylic acid ( 2 ), an analgesic agent.