Methanol → Voriconazole (1R)-(-)-10-camphorsulfonate

Participants

Reaction Steps

Preparation of Racemic Voriconazole (Compound V) from Enantiomeric Pair B of chloroderivative of formula (IV) by classical hydrogenation conditions using Pd/C and sodium acetate in ethanol is shown in scheme 2. Resolution of the obtained racemic Voriconazole (compound V) is performed with (1R)-(−)-10-camphorsulfonic acid (CSA) in 38 volumes of methanol to give (2R,3S)-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)-butan-2-ol (1R)-(−)-10-camphorsulfonate (compound VI), that is, Voriconazole (1R)-(−)-10-camphorsulfonate, as hemimethanolate having a melting point of 176° C. Voriconazole (compound I) is isolated from Voriconazole (1R)-(−)-10-camphorsulfonate (compound VI) using dichloromethane and saturated aqueous sodium bicarbonate and final evaporation of the organic extract. The obtained Voriconazole shows a melting point of 127° C.

Provenance & Evidence