Process for the enzymatic synthesis of (7S)-1-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl) N-methyl methanamine, and application in the synthesis of ivabradine and salts thereof

A process for the synthesis of a compound of formula (IX):

• wherein R1 represents a linear or branched C1-C6alkyl, allyl or benzyl group,
• by enantioselective enzymatic acylation of a racemic amine of formula (IV):
• using a lipase (EC 3.1.1.3 in the international classification of enzymes),
• with a carbonate of formula R1O—(CO)—OR1, wherein R1 is as defined hereinbefore,
• in an amount ranging from 1 to 15 molar equivalents relative to the amine of formula (IV),
• in an organic or aqueous solvent, a mixture of organic solvents or a mixture of organic and aqueous solvents,
• at a concentration from 5 to 500 g/L of compound of formula (IV) per liter of solvent or mixture of solvents,
• at an Enzyme/Substrate ratio (E/S) of from 10/1 to 1/100, at a temperature from 25° C. to 40° C.