反应详情

A mixture of 2-chloro-5-fluoronicotinic acid (2.61 g, 14.9 mmol), 4-fluorophenol (2.02 g, 18 mmol), potassium carbonate (4.56 g, 33 mmol), copper bronze (211 mg, 3.3 mmol), and cuprous iodide (230 mg, 1.2 mmol) in N,N-dimethylforamide (40 mL) was heated under reflux in an oil bath for 6 h. The reaction mixture was filtered through a pad of Celite®. The filtrate was partitioned between ethyl acetate (200 mL) and 2 N hydrochloric acid (200 mL). The organic phase was separated and the aqueous phase was extracted with ethyl acetate (200 mL). The combined organic extracts were washed with brine (50 mL) and dried (sodium sulfate). After removal of solvent, the residual oil was dissolved in methanol (50 mL). To the solution were added conc. hydrochloric acid (1 mL) and the mixture was heated under reflux for 4 h. The volatile components were removed under reduced pressure, and the residue was purified by flash column chromatography on silica gel (150 g) eluting with hexane/ethyl acetate (3/1) to afford 2.63 g (67%) of the title compound: 1H-NMR (CDCl3) δ 8.11 (1H, d, J=3.1 Hz), 8.02 (1H, dd, J=7.7, 3.1 Hz), 7.11–7.07 (4H, m), 3.96 (3H, s); MS (ESI) m/z 266 (M+H)+.

1. temperaturewas heated
2. temperatureunder reflux in an oil bath for 6 h
3. filtrationThe reaction mixture was filtered through a pad of Celite®
4. customThe filtrate was partitioned between ethyl acetate (200 mL) and 2 N hydrochloric acid (200 mL)
5. customThe organic phase was separated
6. extractionthe aqueous phase was extracted with ethyl acetate (200 mL)
7. washThe combined organic extracts were washed with brine (50 mL)
8. dry with materialdried (sodium sulfate)
9. customAfter removal of solvent
10. dissolutionthe residual oil was dissolved in methanol (50 mL)
11. additionTo the solution were added conc. hydrochloric acid (1 mL)
12. temperaturethe mixture was heated
13. temperatureunder reflux for 4 h
14. customThe volatile components were removed under reduced pressure
15. customthe residue was purified by flash column chromatography on silica gel (150 g)
16. washeluting with hexane/ethyl acetate (3/1)