Process for the preparation of a cyano-isobenzofuran

A process for the preparation of citalopram or of a pharmaceutically acceptable salt thereof, which comprises:

• (a) reacting 5-cyanophthalide with a 4-fluorophenylmagnesium halide;
• (b) treating the mixture thus obtained, containing the 3-hydroxymethyl-4-(4-fluorobenzoyl)benzonitrile and the 3-hydroxymethyl-4-[bis-(4fluorophenyl)hydroxymethyl]benzonitrile with a reducing agent of ketones to alcohols;
• (c) submitting the mixture thus obtained, containing the 3-hydroxymethyl-4-[(4-fluorophenyl)hydroxymethyl]benzonitrile (C) and the 3-hydroxymethyl-4-[bis-(4-fluorophenyl)hydroxymethyl]benzonitrile to a cyclization reaction and isolating a mixture containing the 1-(4-fluorophenyl)-1,3-dihydro-5-isobenzofurancarbonitrile (B) and the 1,1-bis(4-fluorophenyl)-1,3-dihydro-5-isobenzofurancarbonitrile;
• (d) treating the mixture thus obtained with a solvent capable of dissolving the 1,1-bis(4-fluorophenyl)-1,3-dihydro-5-isobenzofurancarbonitrile and in which the 1-(4-fluorophenyl)-1,3-dihydro-5-isobenzofurancarbonitrile (B) is insoluble and recovering the pure 1-(4-fluorophenyl)-1,3-dihydro-5-isobenzofurancarbonitrile (B), wherein said solvent is isopropanol or methyl-t-butylether;
• (e) treating the pure 1-(4-fluorophenyl)-1,3-dihydro-5-isobenzofurancarbonitrile (B) with a 3-(dimethylamino)propyl halide in the presence of a basic condensing agent and isolating citalopram as free base or as a pharmaceutically acceptable salt thereof.