1H-1,2,4-Triazole → 2-(2,4-difluorophenyl)-3-(3,4,5,6-tetrahydro-2H-pyran-2-yl)oxy-1-(1H-1,2,4-triazol-1-yl)-2-butanol

Participants

Reaction Steps

To N,N-dimethylformamide (700 ml) was added, at room temperature while stirring, 60% sodium hydride in oil (35.2 g) by portions during 10 minutes. The mixture was stirred for 5 minutes at room temperature, to which was added 1H-1,2,4-triazole (25 g) by portions at room temperature during 20 minutes. The reaction mixture was cooled with ice, to which was added 1H-1,2,4-triazole (44.6 g) during 30 minutes with stirring, followed by stirring at room temperature for further 10 minutes. To the resultant mixture was added dropwise 2-[1-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)ethyl]-2-(2,4-difluorophenyl)oxirane (83.4 g) during 5 minutes, which was stirred for 4 hours at 90° C. The reaction mixture was cooled and poured into ice-water (1.5 l), which was subjected to extraction with ethyl acetate (500 ml) for 4 times. The ethyl acetate layer was washed with water (300 ml) 3 times and dried over anhydrous magnesium sulfate. Then the solvent was distilled off to leave a pale yellow oily product. This product was purified by means of a silica gel column chromatography (hexane:acetone=4:1~1:1). The resultant oily product was crystallized from hexane to give 2-(2,4-difluorophenyl)-3-(3,4,5,6-tetrahydro-2H-pyran-2-yl)oxy-1-(1H-1,2,4-triazol-1-yl)-2-butanol (51.4 g) as colorless powder, m.p. 93°-95° C. Elemental Analysis for C17H21F2N3O3 : Calcd.: C, 57.78; H, 5.99; N, 11.89 Found: C, 57.82; H, 6.04; N, 11.77.

Provenance & Evidence