Process Optimization in the Synthesis of Sertindole Using Alkylimidazolium-based Ionic Liquids as Solvents for N-alkylation

Sertindole is a well-known antipsychotic drug. Its chemical name is 1-[2 -[4-[5 - chloro - 1- (4 - fluorophenyl) - 1 - H - indol - 3 - yl] - 1-piperidinyl] ethyl] - 2 - imidazolidinone. Sertindole was originally produced via the 1 - (2 - chloroethyl) - 2 - imidazolidinon with N-alkylation of 5 -- chloro - 1 - (4 - fluorophenyl) - 3 - (piperidine - 4 - yl) in dole in methyl isobutyl ketone for 12h. This step required significant optimization to improve yield and reproducibility. Under common conditions, the solvent play an important role in the N-alkylation reaction. Ionic liquid is a new kind reaction medium which have environmentally friendly characteristic. Basic ionic liquid [bmin]OH was found to be a suitable solvent for the N-alkylation. A robust production process of Sertindole was obtained through the solvent optimization. The modification and process improvement was scaled-up successfully to batch sizes of > 1 kg.