反应详情

To a stirred solution of 2,6-difluoro-N-1H-pyrazol-3-ylbenzamide (for a preparation see Intermediate 9)(100 mg, 0.448 mmol) in dry THF (6.0 ml) under nitrogen at ambient temperature was added 1.0 M lithium bis(trimethylsilyl)amide (0.45 ml, 0.45 mmol) dropwise and then the solution stirred for approximately 30 min. To the solution was added a solution of crude 2-(bromomethyl)-4-(phenyloxy)-1-(trifluoromethyl)benzene (0.135 g) in dry THF (2.5 ml) and stirred for 7 h. The solvent was removed using a stream of nitrogen. To the residue was added saturated aqueous sodium bicarbonate (approximately 7 ml) and then the residue extracted three times with chloroform. The combined organic extracts were filtered through a hydrophobic frit. The solvent was removed in vacuo and the residue purified on MDAP (Method B). The appropriate fractions were combined and solvent evaporated in vacuo. The residue was dried under high vacuum at 45° C. to give the title compound as a white solid (85 mg); LCMS: (System 4) MH+=474, tRET=3.30 min.

1. customat ambient temperature
2. stirringstirred for 7 h
3. customThe solvent was removed
4. additionTo the residue was added saturated aqueous sodium bicarbonate (approximately 7 ml)
5. extractionthe residue extracted three times with chloroform
6. filtrationThe combined organic extracts were filtered through a hydrophobic frit
7. customThe solvent was removed in vacuo
8. customthe residue purified on MDAP (Method B)
9. customsolvent evaporated in vacuo
10. customThe residue was dried under high vacuum at 45° C.