反应详情

温度

80 °C

To a solution of 2-hydroxy-5-(trifluoromethoxy)phenylboronic acid (Preparation 23, 20.5 g, 92.4 mmol) and 4-bromo-3-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole or 4-bromo-5-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole (Preparation 22, 22.7 g, 82.2 mmol) in 1,2-dimethoxyethane (300 mL) and 2 M potassium carbonate in water (117 mL, 212 mmol) was added tetrakis(triphenylphosphine)palladium(0) (5.0 g, 4.3 mmol). The solution was sparged with argon (×3) and heated at 80° C. for 8 hours. The reaction mixture was cooled to ambient temperature and the layers separated. The aqueous phase was washed with ethyl acetate (×2). The combined organic phase was dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography (0 to 30% ethyl acetate in hexanes gradient elution) and concentrated in vacuo. Excess hexanes was added to the residue and the resulting solid was collected by filtration and dried in vacuo to afford the title compound as off white crystals (19.5 g).

1. customThe solution was sparged with argon (×3)
2. temperatureThe reaction mixture was cooled to ambient temperature
3. customthe layers separated
4. washThe aqueous phase was washed with ethyl acetate (×2)
5. dry with materialThe combined organic phase was dried over anhydrous magnesium sulfate
6. concentrationconcentrated in vacuo
7. customThe residue was purified by silica gel column chromatography (0 to 30% ethyl acetate in hexanes gradient elution)
8. concentrationconcentrated in vacuo
9. additionExcess hexanes was added to the residue
10. filtrationthe resulting solid was collected by filtration
11. customdried in vacuo