Hydrochloric Acid → Posaconazole

Participants

Reaction Conditions

Reaction Steps

5N hydrochloric acid (72 ml) and 10% Pd—C(10 g) were added to a solution of 4-(4-(4-(4-(((3R,5R)-5-((1H-1,2,4-triazol-1-yl)methyl)-5-(2,4-difluorophenyl)tetrahydro furan-3-yl)methoxy)phenyl)piperazin-1-yl)phenyl)-1-((2S,3R)-2-(benzyloxy)pentan-3-yl)-1H-1,2,4-triazol-5(4H)-one compound of formula-21 (42 g) in methanol (420 ml). The reaction mixture was hydrogenated for 5 hours under a hydrogen gas pressure of 4-5 kg/cm2 at 50°. After completion of reaction, the catalyst was filtered off and washed with methanol. pH of the filtrate was adjusted to ˜7.0 using 4N sodium hydroxide. Water was added to the reaction mixture and stirred for 2 hours at 25-35° C. Filtered the separated solid and washed with water. The obtained solid was dissolved in acetone (320 ml) and stirred at reflux temperature for 30 minutes. Filtered the undissolved product and added water to the filtrate and stirred the reaction mixture for 4 hours at 25-35° C. Filtered the separated solid and washed with water. Further the solid was recrystallized from isopropyl alcohol to get the title compound. Purity by HPLC: 99.85%; Yield: 75.0%: Chiral purity by HPLC: 99.82%.

Provenance & Evidence