Process for the enzymatic synthesis of (7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-triene-7-carboxylic acid and application in the synthesis of ivabradine and salts thereof

摘要

The invention relates to a process for the enzymatic synthesis of the compound of formula (I):by enantioselective enzymatic hydrolysis of the racemic, or not optically pure, nitrile of formula (IV):using the nitrilase of Rhodococcus rhodochrous NCIMB 11216 over-expressed in another organism having a competent biological system, in a mixture of an organic solvent and an aqueous solution having a pH from 5 to 10, at a concentration from 1 to 500 g of nitrile of formula (IV) per litre of solvent mixture, at an E/S ratio of from 1/1 to 1/10, at a temperature from 25°C to 40°C.