Lithium Hexamethyldisilazide → 2,6-difluoro-N-{1-[(2-methyl-5-nitrophenyl)methyl]-1H-pyrazol-3-yl}benzamide

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Reaction Steps

To a solution of 2,6-difluoro-N-1H-pyrazol-3-ylbenzamide (for a preparation see Intermediate 9) (1.80 g, 8.07 mmol) in THF (30 ml) at ambient temperature under nitrogen was added 1.0 M lithium bis(trimethylsilyl)amide in THF (8 mL, 8.00 mmol) and stirred for 20 min. To the solution was added a solution of 2-(bromomethyl)-1-methyl-4-nitrobenzene (1.81 g, 7.87 mmol) in THF (20 ml) and stirred overnight. The solvent was removed in vacuo and the residue partitioned between ethyl acetate (150 ml) and saturated aqueous sodium hydrogen carbonate (50 ml). The phases were separated and the aqueous phase washed with ethyl acetate (25 ml). The combined organic extracts were dried (MgSO4), filtered and the solvent removed in vacuo to leave a yellow oil (3.5 g). The residue was loaded in dichloromethane and purified on silica 100 g using 0-100% ethyl acetate-cyclohexane. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a white foam (2.1 g); LCMS (System 4) MH+=373, tRET=2.60 min.

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