Lithium Hexamethyldisilazide → HCID 59547920, compound

Participants

Reaction Steps

To a solution of 2,6-difluoro-N-(1H-pyrazol-3-yl)benzamide (for a preparation see Intermediate 9)(3.9 g, 17.5 mmol) in THF (35 ml) at ambient temperature was added 1.0 M lithium bis(trimethylsilyl)amide in THF (17.5 ml, 17.50 mmol, Aldrich) dropwise. The solution was stirred for 20 min. To the solution was added a solution of 2-(bromomethyl)-4-nitro-1-(trifluoromethyl)benzene (7.3 g, 25.7 mmol) in THF (10 ml). The resulting dark brown solution was stirred at ambient temperature for 4.5 h. The solvent was removed in vacuo and the residue partitioned between ethyl acetate (125 ml) and saturated aqueous sodium hydrogen carbonate (75 ml). The phases were separated and the organic phase washed with saturated aqueous sodium hydrogen carbonate (25 ml), dried (MgSO4), filtered and the solvent removed in vacuo to leave a brown oil (˜11 g). The residue was loaded in dichloromethane and purified on silica 100 g×2 using 0-100% ethyl acetate-cyclohexane. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a yellow solid (4.31 g); LCMS: (System 4) MH+=427, tRET=2.80 min.

Provenance & Evidence