N,N,N',N'-Tetramethylethylenediamine → Citalopram

Participants

Reaction Steps

60% Sodium hydride (0.58 g) was dispersed in THF (12 ml), and to this suspension was added dropwise a solution of 1-(4′-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (3.0 g) in THF (6 ml) at 40-50° C. under a nitrogen atmosphere. Thereto was added tetra n-butylammonium bromide (0.12 g), and a solution of 3-(dimethylamino)propyl chloride (2.0 g) in t-butyl methyl ether (12 ml) was added dropwise, which was followed by stirring for 10 min. Further, N,N,N′,N′-tetramethylethylenediamine (0.73 g) and N,N-dimethylformamide (14.2 g, 15 ml) were added and the mixture was stirred at 61-64° C. for 7 hr. The reaction mixture was treated in the same manner as in Example 22 to give 1-(3-(dimethylamino)propyl)-1-(4′-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (citalopram base) as a viscous oil (3.14 g, yield 77.2%). Hydrobromide thereof showed the same HPLC retention time and melting point as obtained in Example 22.

Provenance & Evidence