反应详情

温度

50 °C

A suspension of 2-bromo-5-fluoropyridin-4-ylboronic acid (1.569 g, 7.14 mmol) and 1,4-difluoro-2-vinylbenzene (1 g, 7.14 mmol) in dimethylformamide (20 mL) was flushed with a balloon of oxygen. To this was added sodium carbonate (1.51 g, 14.3 mmol) and palladium(II) acetate (0.16 g, 0.71 mmol) as solids in one portion. The flask was flushed with another balloon of oxygen and fitted with a balloon of oxygen. The reaction was warmed to 50° C. After 1 h, the reaction was treated with a second portion of sodium carbonate (0.75 g) and boronic acid (1.6 g). This process was repeated twice more (total boronic acid addition=6.3 g). The reaction was cooled to room temperature, diluted with ether, washed with water (3×), then brine, dried over magnesium sulfate, and concentrated. Column chromatography (2.5%→5% EtOAc/Hex) gave 89 mg (4.0%) as a white solid. 1H NMR (CDCl3) Shift: 8.28 (d, J=1.8 Hz, 1H), 7.68 (d, J=5.5 Hz, 1H), 7.49 (d, J=16.5 Hz, 1H), 7.33 (ddd, J=8.9, 5.8, 3.1 Hz, 1H), 7.17 (d, J=16.8 Hz, 1H), 6.98-7.14 (m, 2H). 19F NMR (CDCl3) Shift: −118.54 (d, J=13.0 Hz, 1F), −122.71 (br. s., 1F), −135.71 (br. s., 1F). Mass spec.: 314.0 (MH)+.

1. customwas flushed with a balloon of oxygen
2. customThe flask was flushed with another balloon of oxygen
3. customfitted with a balloon of oxygen
4. additionthe reaction was treated with a second portion of sodium carbonate (0.75 g) and boronic acid (1.6 g)
5. addition(total boronic acid addition=6.3 g)
6. temperatureThe reaction was cooled to room temperature
7. additiondiluted with ether
8. washwashed with water (3×)
9. dry with materialbrine, dried over magnesium sulfate
10. concentrationconcentrated
11. customColumn chromatography (2.5%→5% EtOAc/Hex) gave 89 mg (4.0%) as a white solid