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

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Reaction Steps

The intermediate may be worked up in a conventional manner. The further process leading to sertindole comprises cyclization of N-(4-fluorophenyl)-N-(2-carboxy-4-chlorophenyl)glycine to the corresponding 3-acetoxy-indole using eg. acetic anhydride in the presence of alkalimetal acetate such as sodium acetate. 5-chloro-1-(4-fluoro)indole is then obtained from the 3-acetoxy-indole by reduction and subsequent elimination of H2O. The resulting 5-chloro-1-(4-fluorophenyl)indole is reacted with 4-piperidone according to the above procedure, the resulting 5-chloro-1-(4-fluorophenyl)-3-(1,2,3,6-tetrahydropyridin-4-yl)indole is reduced 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 to obtain sertindole. Alternatively, the 5-chloro-1-(4-fluorophenyl)-3-(1,2,3,6-tetrahydropyridin-4-yl)indole may first be reacted with 1-(2-chloroethyl)-2-imidazolidinon followed by reduction, thereby obtaining sertindole, which may be isolated as an acid addition salt, e.g. the tartrate, or as the free base.

Provenance & Evidence