反应详情

温度

90 °C

To a solution of (1-(tert-butoxycarbonyl)-4-fluoro-1H-indol-2-yl)boronic acid (126 g, 0.45 mol) and 6-chloro-2-iodopyridin-3-ol (96 g, 0.37 mmol) in 1,4-dioxane (1.8 L) and water (0.2 L) were added Pd(PPh3)2Cl2 (13.2 g, 18.6 mmol) and NaHCO3 (94.8 g, 1.13 mol) under nitrogen atmosphere, and the mixture was heated at 90° C. under N2 for 16 h. The reaction mixture was cooled to room temperature, diluted with EtOAc (900 mL), filtered and concentrated. The residue was diluted with H2O (400 mL) and EtOAc (800 mL), and the layer was separated, the aqueous layer was extracted with EtOAc (3*400 mL). The combined organic layers were washed with brine (800 mL), dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography (PE:EtOAc=20:1˜3:1) to give 6-chloro-2-(4-fluoro-1H-indol-2-yl)pyridin-3-ol (70 g, yield: 70.1%). 1H-NMR (MeOD, 400 MHz) δ 7.36 (s, 1H), 7.23˜7.27 (m, 2H), 7.03˜7.11 (m, 2H), 6.63˜6.68 (m, 1H). MS (M+H)+: 263 (M+H).

1. temperatureThe reaction mixture was cooled to room temperature
2. filtrationfiltered
3. concentrationconcentrated
4. additionThe residue was diluted with H2O (400 mL) and EtOAc (800 mL)
5. customthe layer was separated
6. extractionthe aqueous layer was extracted with EtOAc (3*400 mL)
7. washThe combined organic layers were washed with brine (800 mL)
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated
11. customThe residue was purified by column chromatography (PE:EtOAc=20:1˜3:1)