Method for the manufacture of diltiazem

Details Method for the manufacture of diltiazem Method for the manufacture of diltiazem

C - Chemistry, Metallurgy

07

D

C07D 281/02 (2006.01) C07D 281/10 (2006.01)

Patent

CA 2169717

An improved process for preparing diltiazem comprises using a mixture of toluene and N-methylpyrrolidin- 2-one as solvent and finely divided sodium carbonate as a base. The reaction comprises a process for preparing diltiazem according to formula (II), Image (II) characterized in that a compound according to formula (III) Image (III) is allowed to react with a compound according to formula (IV) Image (IV) in a mixture of toluene and N-methylpyrrolidin-2-one in the presence of finely divided sodium carbonate in anhydrous conditions to cis-(+)-hydroxy-5-[2(dimethylamino)ethyl]-2,3- dihydro-2-(4-methoxyphenyl)-benzothiazepin-4(5H)-one accord- ing to formula (I), Image ( I) the solvents are removed by distillation after a water wash of the reaction mixture and the separation of the water layer, and the distillation residue is allowed to react with acetic acid anhydride to form diltiazem (II).

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