反应详情

温度

80 °C

A mixture of N-[1-(4-bromophenyl)ethyl]-5-fluoro-2-(4-fluorophenoxy)nicotinamide (step 1, 398 mg, 0.92 mmol), 1,3-bis(diphenylphosphino)-propane (38 mg, 0.09 mmol), palladium (II) acetate (21 mg, 0.09 mmol), triethylamine (0.38 mL, 2.76 mmol), N,N-dimethylforamide (6 mL) and methanol (4 mL) was stirred at 80° C. for 16 h under carbon monoxide atmosphere. After cooling to room temperature, the mixture was diluted with ether (100 mL) and washed with water (60 mL×3). The organic layer was dried over magnesium sulfate and evaporated. The residue was purified by flush column chromatography on silica gel eluting with hexane/ethyl acetate (2:1) to afford 296 mg (78%) of the title compounds as white solids: 1H-NMR (CDCl3) δ 8.32 (1H, dd, J=8.1, 3.1 Hz), 8.21 (1H, d, J=7.3 Hz), 8.04–7.99 (3H, m), 7.43 (2H, d, J=8.2 Hz), 7.27–7.13 (4H, m), 5.38 (1H, dq, J=7.3, 6.9 Hz), 3.90 (3H, s), 1.60 (3H, d, J=6.9 Hz); MS (ESI) m/z 413 (M+H)+, 411 (M−H)−.

1. temperatureAfter cooling to room temperature
2. washwashed with water (60 mL×3)
3. dry with materialThe organic layer was dried over magnesium sulfate
4. customevaporated
5. customThe residue was purified
6. customby flush column chromatography on silica gel eluting with hexane/ethyl acetate (2:1)