反应详情

1.0 M LiHMDS (5.00 ml, 5.00 mmol) in THF/ethylbenzene was added slowly to a solution of 2,6-difluoro-N-(1H-pyrazol-3-yl)benzamide (for a preparation see Intermediate 9)(1.12 g, 5 mmol) in THF (50 ml) under nitrogen at ambient temperature. The solution was stirred for 20 min and a solution of methyl 3-(bromomethyl)-4-chlorobenzoate (1.32 g, 5.0 mmol, synthesised according to WO2006079857) in THF (4 ml) was added in one portion. The solution was stirred for 2 h and left overnight. The solution was treated with aqueous ammonium chloride (50 ml) and extracted with ethyl acetate (2×50 ml). The combined organic extracts were dried (Na2SO4), filtered and solvent evaporated in vacuo. The residue was purified on a silica cartridge (50 g) eluted with 0-100% cyclohexane/EtOAc to give the title compound (1.95 g) as a white solid after evaporation from diethyl ether; LCMS: (System 4) MH+=406/408, tRET=2.69 min.

1. customat ambient temperature
2. stirringThe solution was stirred for 2 h
3. waitleft overnight
4. extractionextracted with ethyl acetate (2×50 ml)
5. dry with materialThe combined organic extracts were dried (Na2SO4)
6. filtrationfiltered
7. customsolvent evaporated in vacuo
8. customThe residue was purified on a silica cartridge (50 g)
9. washeluted with 0-100% cyclohexane/EtOAc