反应详情

温度

85 °C

To 2-(5-bromo-2-fluorophenyl)-3,5-difluoropyridine (0.746 g, 2.59 mmol) and bis(neopentyl glycolato)diboron (0.704 g) was added dry 1,4-dioxane (9 ml) and dry dimethylsulfoxide (1.1 ml), followed by dry potassium acetate (0.542 g) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (0.080 g). The mixture was thoroughly degassed with nitrogen, and then stirred at 85° C. for 24 h. On cooling to room temperature, 1 N aqueous sodium hydroxide (24 ml) was added, and the mixture stirred for 0.5 h. Diethyl ether was added and the aqueous phase was separated and washed with diethyl ether. The organic extracts were washed with water, and the combined aqueous phases were filtered, then acidified to pH 5 by addition of 2 N aqueous hydrochloric acid (12 ml). The resulting solid was collected by filtration, washed with water, and dried in vacuo at 60° C. to afford 0.618 g of 4-fluoro-3-(3,5-difluoropyridin-2-yl)phenylboronic acid as a colourless solid: 1H NMR (400 MHz, DMSO-d6) δ 8.69 (1H, d, J 2.3 Hz), 8.21 (2H, s), 7.94-8.14 (3H, m), 7.34 (1H, dd, J 8.2, 10.6 Hz).

1. customThe mixture was thoroughly degassed with nitrogen
2. temperatureOn cooling to room temperature
3. addition1 N aqueous sodium hydroxide (24 ml) was added
4. stirringthe mixture stirred for 0.5 h
5. additionDiethyl ether was added
6. customthe aqueous phase was separated
7. washwashed with diethyl ether
8. washThe organic extracts were washed with water
9. filtrationthe combined aqueous phases were filtered
10. additionacidified to pH 5 by addition of 2 N aqueous hydrochloric acid (12 ml)
11. filtrationThe resulting solid was collected by filtration
12. washwashed with water
13. customdried in vacuo at 60° C.