Process for producing acyloxymethyl esters of (4s)-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridin-3-carboxylic acid

A process for preparing (4S)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide of the formula (Ia)

• comprising obtaining racemic acyloxymethyl esters of (4S)-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid of the formula (II)
• where R is a linear or branched C1-C25 chain optionally substituted by an aromatic radical, converting the compound of the formula (II) by optical resolution using a hydrolase to the enantiomeric acyloxymethyl ester of (4S)-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid of the formula (IIa)
• where R is a linear or branched C1-C25 chain optionally substituted by an aromatic radical, hydrolysing the compound of the formula (IIa) to give the compound of the formula (IIIa)
• reacting the compound of the formula (IIIa) in THE as solvent firstly with 1,1-carbodiimidazole optionally with catalytic amounts of 4-(dimethylamino)pyridine, then adding hexamethyldisilazane to form a mixture and heating the mixture under reflux for 16-24 hours, and then adding water or a THF/water mixture to form the compound of the formula (Ia).