反应详情

温度

89 °C

A stirred mixture of (5-bromo-2-pyridinyl)methanol (105) (753 mg, 4.00 mmol), 3-fluoro-4-(trifluoromethoxy)phenylboronic acid (56) (see Example 2G) (1.165 g, 5.20 mmol) and Pd(dppf)Cl2 (366 mg, 0.50 mmol) in toluene (40 mL) and EtOH (20 mL) was degassed for 15 min (vacuum pump) and then N2 was added. An aqueous solution of 2M Na2CO3 (10 mL, 20.0 mmol) was added by syringe and the stirred mixture was again degassed for 15 min, and then N2 was added. The resulting mixture was stirred at 89° C. for 2 h, and then cooled, diluted with aqueous NaHCO3 (120 mL) and extracted with CH2Cl2 (6×100 mL). The extracts were evaporated to dryness and the residue was chromatographed on silica gel. Elution with 50-75% CH2Cl2/petroleum ether firstly gave foreruns, and then further elution with 75% CH2Cl2/petroleum ether and 0-0.5% MeOH/CH2Cl2 gave {5-[3-fluoro-4-(trifluoromethoxy)phenyl]-2-pyridinyl}methanol (106) (687 mg, 60%) as a light yellow-brown solid: mp 51-53° C.; 1H NMR (CDCl3) δ 8.76 (d, J=1.9 Hz, 1H), 7.84 (dd, J=8.1, 2.3 Hz, 1H), 7.46-7.34 (m, 4H), 4.83 (d, J=5.1 Hz, 2H), 3.47 (t, J=5.2 Hz, 1H); HRESIMS calcd for C13H10F4NO2m/z [M+H]+ 288.0642, found 288.0641.

1. customwas degassed for 15 min (vacuum pump)
2. additionN2 was added
3. customthe stirred mixture was again degassed for 15 min
4. additionN2 was added
5. temperaturecooled
6. additiondiluted with aqueous NaHCO3 (120 mL)
7. extractionextracted with CH2Cl2 (6×100 mL)
8. customThe extracts were evaporated to dryness
9. customthe residue was chromatographed on silica gel
10. washElution with 50-75% CH2Cl2/petroleum ether firstly gave foreruns
11. washfurther elution with 75% CH2Cl2/petroleum ether and 0-0.5% MeOH/CH2Cl2