反应详情

温度

105 °C

A suspension of (2,4-dichlorophenyl)methanol (4.10 g, 23.2 mmol), 2-chloro-4-iodopyridine (5.05 g, 21.1 mmol), Cs2CO3 (8.94 g, 27.4 mmol), CuI (4.01 g, 21.1 mmol) and 1,10-phenanthroline (760 mg, 4.22 mmol) in toluene (20 mL) was degassed by bubbling N2 through the suspension for 15 min. The suspension was put under N2, and heated at 105° C. for 18 h. The suspension was cooled, EtOAc (50 mL) was added, and the resulting suspension was passed through a plug of SiO2. The resulting solution was concentrated under reduced pressure. Flash chromatography on silica gel (hexanes/(1:1 EtOAc/hexanes), 100:0 to 0:100) afforded a white solid. A suspension of the white solid and NH4OAc (6.13 g, 79.5 mmol) in 1:1 HCO2H/H2O (40 mL) was heated at reflux with stirring for 4 d. The solution was cooled and concentrated under reduced pressure. The resulting residue was made basic with saturated NaHCO3 solution and the resulting suspension was filtered. The solid was washed with H2O and dried under reduced pressure. Flash chromatography on silica gel ((1:1 EtOAc/hexanes)/(9:0.9:0.1 CH2Cl2/MeOH/NH4OH), 100:0 to 0:100) afforded 1.36 g (24%) of the title compound as a white solid: 1H NMR (300 MHz, DMSO-d6) δ 11.16 (br s, 1H), 7.71 (d, J=2.1 Hz, 1H), 7.61 (d, J=8.1, 1H), 7.50 (dd, J=8.4, 2.1 Hz, 1H), 7.26 (d, J=7.2 Hz, 1H), 5.91 (dd, J=7.5, 2.7 Hz, 1H), 5.81 (d, J=2.4 Hz, 1H), 5.10 (s, 2H).

1. customwas degassed
2. customby bubbling N2 through the suspension for 15 min
3. temperatureThe suspension was cooled
4. additionEtOAc (50 mL) was added
5. concentrationThe resulting solution was concentrated under reduced pressure
6. customFlash chromatography on silica gel (hexanes/(1:1 EtOAc/hexanes), 100:0 to 0:100) afforded a white solid
7. temperaturewas heated
8. temperatureat reflux
9. temperatureThe solution was cooled
10. concentrationconcentrated under reduced pressure
11. filtrationthe resulting suspension was filtered
12. washThe solid was washed with H2O
13. customdried under reduced pressure