反应详情

温度

90 °C

In a 500 mL flask was placed 1,1-dimethylethyl carbamate (6.03 g, 51.5 mmol), methyl 3-bromo-2-fluorobenzoate (10 g, 42.9 mmol), Pd2(dba)3.CHCl3 (0.89 g, 0.86 mmol), xantphos (1.49 g, 2.57 mmol) and cesium carbonate (16.8 g, 51.5 mmol). The flask was sealed with a rubber septum, placed under high vacuum, and toluene (200 mL) was added. Three cycles of high vacuum/N2 were performed and the reaction mixture was stirred at 90° C. overnight. The reaction was filtered through a pad of celite with EtOAc washing and concentrated. To the residue was added DCM (200 mL) followed by TFA (50 mL, 649 mmol), and the mixture was stirred at rt for 1 h. The volatiles were removed under reduced pressure and the residue was taken up in EtOAc and washed with saturated NaHCO3 and brine. The organic layer was dried over NaSO4, stripped onto silica and column chromatographed on silica with 5% to 50% EtOAc:Hexane to give 5.53 g (76%) of the title compound of Step B. 1H-NMR (400 MHz, DMSO-d6) δ 6.92-7.01 (m, 3H), 5.37 (s, 2H), and 3.81 (s, 3H). MS (ESI): 170 [M+H]+.

1. customIn a 500 mL flask was placed
2. customThe flask was sealed with a rubber septum
3. additionwas added
4. filtrationThe reaction was filtered through a pad of celite with EtOAc washing
5. concentrationconcentrated
6. additionTo the residue was added DCM (200 mL)
7. stirringthe mixture was stirred at rt for 1 h
8. customThe volatiles were removed under reduced pressure
9. washwashed with saturated NaHCO3 and brine
10. dry with materialThe organic layer was dried over NaSO4
11. customchromatographed on silica with 5% to 50% EtOAc