Synthesis of Isomeric and Potent Impurities of the Triazole-Based Antifungal Drug Voriconazole.

We describe the synthesis of two positional isomers and a desfluoro impurity of Voriconazole starting with Friedel-Crafts acylation of mono- and difluorobenzene. These isomers are the crucial components in determining the quality of Voriconazole during its manufacturing from the key raw material, 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethan-1-one. All the prepared impurities were characterized by IR, (1)H-NMR, (13)C-NMR, and mass spectral data.