反应详情

A mixture of Pd(PPh3)2Cl2 (0.42 g, 0.57 mmol) and 2-bromo-5-hydroxypyridine (1.0 g, 5.75 mmol) in DME (20 mL) was degassed with N2. 2M Na2CO3 (10 mL) was added, and the mixture was stirred at ambient temperature for 10 minutes. 4-Bromo-2-fluorobenzeneboronic acid (1.48 g, 6.61 mmol) was added. The reaction mixture was degassed again, purged with N2 and heated at 80° C. overnight, then cooled to ambient temperature, and partitioned between water and EtOAc. Concentrated HCl was added carefully to adjust aqueous pH to about 8, the mixture was filtered thought Celite®, and the EtOAc layer was separated and washed with brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give the crude product as a dark brown oil. The crude product was purified by chromatography on a silica gel column eluted with 20% EtOAc/hexane to give 0.168 g of 6-(4-bromo-2-fluorophenyl)-3-pyridinol as an off-white solid. The impure fractions were combined, concentrated and further purified with 1:5 acetone/hexane to give additional 78 mg of 6-(4-bromo-2-fluorophenyl)-3-pyridinol (0.246 g overall, 16% yield). 1H NMR (400 MHz, CD3OD): δ 8.20 (d, 1H, J=2.7 Hz), 7.75-7.65 (m, 1H), 7.62 (dd, 1H, Ja=8.7 Hz, Jb=2.1 Hz), 7.50-7.40 (m, 2H), 7.28 (dd, 1H, Ja=8.5 Hz, Jb=2.9 Hz); LRMS (ESI), m/z 268/270 (M+H).

1. customwas degassed with N2
2. addition2M Na2CO3 (10 mL) was added
3. customThe reaction mixture was degassed again
4. custompurged with N2
5. temperatureheated at 80° C. overnight
6. temperaturecooled to ambient temperature
7. custompartitioned between water and EtOAc
8. additionConcentrated HCl was added carefully
9. filtrationthe mixture was filtered
10. customthe EtOAc layer was separated
11. washwashed with brine
12. dry with materialdried over Na2SO4
13. filtrationfiltered
14. concentrationthe filtrate was concentrated
15. customto give the crude product as a dark brown oil
16. customThe crude product was purified by chromatography on a silica gel column
17. washeluted with 20% EtOAc/hexane