Dynamic Kinetic Resolution of 2,3‐Dihydrobenzo[ b ]furans: Chemoenzymatic Synthesis of Analgesic Agent BRL 37959

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.