Facile Synthesis, Isolation and Characterization of1-(4-Hydroxy-3-methoxyphenyl)ethanone (Acetovanillone) and its IsomericRelated Substances as Key Starting Materials for an Antipsychotic Drug: Iloperidone

Three isomeric and one process related substances of acetovanillone 1-(4-hydroxy-3- methoxyphenyl)ethanone (I) were isolated and characterized while developing a laboratory process and pilot scale synthesis of acetovanillone. These impurities namely, 1-(3-hydroxy-4- methoxyphenyl)ethanone (Imp 1) (isoacetovanillone impurity), 1-(4-hydroxy-3-methoxyphenyl)- propan-1-one) (Imp 2) (propiovanillone impurity), 1-(3-hydroxy-2-methoxyphenyl)ethanone (Imp 3) (O-acetoisovanillone impurity-1), 1-(2-hydroxy-3-methoxyphenyl)ethanone (Imp 4) (O-acetoisovanillone impurity-2) have been synthesized and reported for the first time. The spectral characteristics of the synthesized impurities were confirmed with FTIR, 1H NMR and mass spectrometry.