反应详情

To a solution of 2,6-difluoro-N-1H-pyrazol-3-ylbenzamide (for a preparation see Intermediate 9)(3 g, 13.4 mmol) in THF (30 ml) was added 1.0 M lithium bis(trimethylsilyl)amide in THF (13.5 ml, 13.5 mmol, Aldrich). The resulting orange solution was stirred at ambient temperature under nitrogen for 30 min. To the reaction was added a solution of 1-(bromomethyl)-4-chloro-2-(trifluoromethyl)benzene (3.7 g, 13.5 mmol, Fluorochem) in THF (5 ml). The resulting orange solution was stirred at ambient temperature under nitrogen overnight. The solvent was removed in vacuo and the residue partitioned between ethyl acetate (125 ml) and aqueous sodium bicarbonate (75 ml). The phases were separated and the organic phase washed with aqueous sodium bicarbonate (50 ml). The combined aqueous phases were washed with ethyl acetate (75 ml). The organic phases were combined, dried, filtered and the solvent removed in vacuo. The residue was loaded in dichloromethane and purified on silica 100 g×2 using a 0-50% ethyl acetate-cyclohexane. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a yellow solid (2.83 g); LCMS: (System 4) MH+=416, tRET=3.14 min.

1. stirringThe resulting orange solution was stirred at ambient temperature under nitrogen overnight
2. customThe solvent was removed in vacuo
3. customthe residue partitioned between ethyl acetate (125 ml) and aqueous sodium bicarbonate (75 ml)
4. customThe phases were separated
5. washthe organic phase washed with aqueous sodium bicarbonate (50 ml)
6. washThe combined aqueous phases were washed with ethyl acetate (75 ml)
7. customdried
8. filtrationfiltered
9. customthe solvent removed in vacuo
10. custompurified on silica 100 g×2 using a 0-50% ethyl acetate-cyclohexane
11. customevaporated in vacuo