反应详情

To a suspension of NaH (38.5 g, 60% in mineral oil, 0.962 mol, washed with hexane three times) in DMF (1 L) cooled in an ice-bath was added triazole (133 g, 1.92 mol) portionwise over a period of 30 min. After completion of the addition, the mixture was warmed to room temperature. The above crude 2-(2,5-Difluorophenyl)-2-[(1R)-1-(3,4,5,6,-tetrahydro-2H-pyran-2-yloxy)ethyl]oxirane was added and the mixture was heated at 70° C. for 8 h. After cooling to room temperature, the reaction mixture was quenched with water (1 L) and the mixture was extracted with EtOAc (1 L×3). The EtOAc layer was combined and washed with water and brine, dried over MgSO4, and evaporated under reduced pressure. The portion of residue was chromatographed on silicagel for analysis (n-hexane: EtOAc=4:1˜1:5) to give pure (3R)-2-(2,5-difluorophenyl)-3-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)-1-(1H-1,2,4-triazol-1-yl)-2-butanol.

1. temperaturecooled in an ice-bath
2. additionAfter completion of the addition
3. temperaturethe mixture was heated at 70° C. for 8 h
4. temperatureAfter cooling to room temperature
5. customthe reaction mixture was quenched with water (1 L)
6. extractionthe mixture was extracted with EtOAc (1 L×3)
7. washwashed with water and brine
8. dry with materialdried over MgSO4
9. customevaporated under reduced pressure
10. customThe portion of residue was chromatographed on silicagel for analysis (n-hexane: EtOAc=4:1˜1:5)