4-Piperidone → 5-Chloro-1-(4-fluorophenyl)-3-(piperidin-4-yl)-1H-indole

Participants

Reaction Steps

Perregaard et al., J Med. Chem, 1992, 35, 1092-1101, disclosed a new method of preparing sertindole. This method comprises reaction of the intermediate 5-chloro-1-(4-fluorophenyl)indole with 4-piperidone in a mixture of trifluoroacetic acid and acetic acid, reduction of the resulting 5-chloro-1-(4-fluorophenyl)-3-(1,2,3,6-tetrahydropyridin-4-yl)indole in order to obtain 5-chloro-1-(4-fluorophenyl)-3-(piperidin-4-yl)indole which in turn is reacted with 1-(2-chloroethyl)-2-imidazolidinon in the presence of K2CO3 and KI in methyl isobutyl ketone (MIBK). The 5-chloro-1-(4-fluorophenyl)indole was obtained from the corresponding 3-acetoxy-indole by NaBH4 reduction in methanol and subsequent elimination of H2O under acidic conditions. The 3-acetoxy-indole was prepared from the N-(4fluorophenyl)-N-(2-carboxy-4-chlorophenyl)glycine following literature procedures.

Provenance & Evidence