反应详情

温度

85 °C

A solution of 5-bromo-2-nitropyridine (15 g, 73.9 mmol) in DMF (300 mL) was sparged with Ar, treated with Cs2CO3 (48.2 g, 148 mmol) and 2-chloro-4-hydroxypyridine (10.53 g, 81 mmol), sparged again with Ar and heated at 85° C. overnight. The mixture was cooled to RT, filtered through a bed of silica gel, washed thoroughly with EtOAc, and the filtrate treated with 5% LiCl and stirred overnight. The layers were separated, the aqueous layer extracted with additional EtOAc (4×) and the combined organics were dried over Na2SO4 and concentrated to dryness. The residue was dissolved in EtOAc, treated with 5% LiCl, stirred for 1 h, the layers separated and the aqueous layer extracted with EtOAc (3×). The combined organics were dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (EtOAc/Hex). The material was suspended in MTBE, sonicated and the resulting solid collected via filtration to afford 2-chloro-4-((6-nitropyridin-3-yl)oxy)pyridine (6.06 g, 33%). 1H NMR (400 MHz, DMSO-d6): δ 8.62 (d, J=2.4, 1H), 8.43-8.39 (m, 2H), 8.06 (dd, J=8.8, 2.8 Hz, 1H), 7.36 (d, J=2.0 Hz, 1H), 7.23 (dd, J=5.6, 2.0 Hz, 1H); MS (ESI) m/z: 252.0 (M+H+).

1. customsparged again with Ar
2. temperatureThe mixture was cooled to RT
3. filtrationfiltered through a bed of silica gel
4. washwashed thoroughly with EtOAc
5. additionthe filtrate treated with 5% LiCl
6. customThe layers were separated
7. extractionthe aqueous layer extracted with additional EtOAc (4×)
8. dry with materialthe combined organics were dried over Na2SO4
9. concentrationconcentrated to dryness
10. dissolutionThe residue was dissolved in EtOAc
11. additiontreated with 5% LiCl
12. stirringstirred for 1 h
13. customthe layers separated
14. extractionthe aqueous layer extracted with EtOAc (3×)
15. dry with materialThe combined organics were dried over Na2SO4
16. concentrationconcentrated to dryness
17. custompurified via silica gel chromatography (EtOAc/Hex)
18. customsonicated
19. filtrationthe resulting solid collected via filtration