Hydrochloric Acid → ent-Voriconazole

Participants

Reaction Conditions

Reaction Steps

13.3 g of zinc powder treated with 1N HCl was dissolved in 300 ml of tetrahydrofuran and refluxed for 1 hour. The resulting solution was cooled to 50° C., and 20 g of (2R,3S)/(2S,3R)-3-[6-(4-chloro-phenylsulfanyl)-5-fluoro-pyrimidine-4-yl]-2-(2,4-difluoro-phenyl)-1-[1,2,4]triazol-1-yl-butane-2-ol obtained in Example 1 or 2 was added thereto. 7.71 g of ammonium formate dissolved in 200 ml of water was slowly added to the resulting mixture for 30 min, and refluxed for 4 hours. The reaction solution was cooled to room temperature, filtered and washed with 200 ml of ethyl acetate. The resulting residue was washed with 200 ml of saturated ammonium chloride aqueous solution, and the water layer was removed therefrom. The organic layer was washed with 200 ml of sodium bicarbonate and 200 ml of brine, and dried over magnesium sulfate. 200 ml of ethyl acetate and 100 ml of hexane were added to the resulting residue, and 9 ml of concentrated HCl was added thereto for crystallization. 200 ml of ethyl acetate and 200 ml of sodium bicarbonate were added to the obtained solid mixture and stirred for 10 min, and the resulting solid was filtered out by using celite. The resulting organic layer was washed with 200 ml of a 5% sodium hydroxide aqueous solution and concentrated under a reduced pressure to obtain the crystallized title compound (12.7 g, yield: 90%).

Provenance & Evidence