N-methyl-2-pyrrolidone → 1-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-1,2,3-triazol-1-yl)phenyl]-2(1H,3H)-imidazolone

Participants

Reaction Steps

To a mixture of 1-[4-(1H-1,2,3-triazol-1-yl)phenyl]-2(1H,3H)-imidazolone (2.72 g) and 1-methyl-2-pyrrolidone (100 ml) was added sodium hydride (70% in oil, 0.40 g), and the mixture was stirred at room temperature for 1 hour. (2R,3S)-2-(2,4-Difluorophenyl)-3-methyl-2-(1H-1,2,4-triazol-1-yl)methyloxirane (2.51 g) was added thereto, and the mixture was stirred at 100° C. for 8 hours under an argon atmosphere. After cooling, the reaction solution was diluted with ethyl acetate (400 ml), and washed with water (100 ml), 1N-hydrochloric acid (100 ml×2) and a saturated aqueous solution of sodium chloride (50 ml) successively. The ethyl acetate layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluent: ethyl acetate to ethyl acetate/acetone=5/1) and recrystallized from ethyl acetate-diisopropyl ether to give 1-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-1,2,3-triazol-1-yl)phenyl]-2(1H,3H)-imidazolone (Compound 11; 1.82 g) as a pale yellow crystalline powder.

Provenance & Evidence