Abstract: A process for one pot synthesis of citalopram is disclosed. The process comprises subjecting 5-cyano phthalide to Grignard reduction followed cyclization and followed by C-alkylation reaction to obtain citalopram without isolation and purification of any intermediates. In another embodiment, 5-cyano phthalide is subjected to sequential Grignard reactions followed by cyclization to obtain citalopram without isolation and purification of any intermediate stages.

Abstract: A method is provided for the isolation of high purity crystalline citalopram (1-[3-dimethylamino)propyl}-1-(4-fluorophenyl)-1, 3-dihydro-5-isobenzofurancarbonitrile) base directly from the alkylation reaction mixture of 5-cyanophthalane with N,N-dimethylaminoprpylchloride in a polar aprotic solvent using a strong base. The method comprises: (a) diluting the reaction mixture with ice cold water and extracting the resulting mixture with a water-immiscible organic solvent; (b) re-extracting the water-immiscible organic solvent extract with an aqueous acid; (c) diluting the aqueous acid extract with a substantially equal volume of a water miscible organic solvent, based on the volume of water in the aqueous acid extract; (d) adjusting the pH to basic with an inorganic base to precipitate free crystalline base and (e) further isolating the precipitated free crystalline base by filration.

Abstract: The present invention provides a process for the preparation of a 5-substituted-1-(4-fluorophenyl)-1,3-dihydro-isoben-zofuran of Formula (2), an intermediate for the manufacture of citalopram, which process comprises: (a) carrying out a Grignard reaction on a corresponding 5-substituted phthalide of Formula (3) in a co-solvent system, comprising adding (i) prepared 4-fluorophenyl magnesium halide in an ether solvent to (ii) the 5-substituted phthalide in a suitable organic co-solvent to the ether solvent, to form a corresponding 4-substituted-2-hydroxymethyl-4?-fluorobenzophenone of Formula (4); (b) carrying out a ketone reduction of the 4-substituted-2-hydroxymethyl-4?-fluorobenzophenone of Formula (4) following the Grignard reaction, to form a corresponding 4-substituted-2-hydroxymethylphenyl-1-(4-fluorophenyl) methanol of Formula (5); and (c) carrying out a cyclisation reaction on the 4-substituted-2 hydroxymethylphenyl-1-(4-fluorophenyl) methanol of Formula (5) following the reduction reaction, to form s