Sodium hydride → 1-[(1R,2R)-1-Methyl-2-hydroxy-2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazole-1-yl)propyl]-3-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-4-imidazoline-2-one

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Reaction Steps

60% Sodium hydride in oil (2.4 g) was added portionwise to a stirred solution of 1-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-2(1H,3H)-imidazolone (16.6 g) and the resulting mixture was stirred for 30 minutes at room temperature. (2R,3S)-2-(2,4-Difluorophenyl)-3-methyl-2-(1H-1,2,4-triazol-1-yl)methyloxirane (10 g) was added and the mixture was stirred at 80° C. for 20 hours. After cooling, the mixture was concentrated into a volume of about 50 ml under reduced pressure and diluted ice-water (400 ml) and ethyl acetate (500 ml). The ethyl acetate layer was separated, washed with a 10% aqueous phosphoric acid solution (400 ml) and an aqueous solution of sodium chloride (400 ml×2) successively and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=1/1 to 2/1) to give 1-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-2(1H,3H)-imidazolone (7.56 g) as an oily substance, which was identical with the compound obtained in the Reference Example 47.

Provenance & Evidence