反应详情

To a solution of 4-fluorophenol (224 mg, 2.0 mmol) in DMF (5.0 mL) was added sodium hydride (48 mg, 2.0 mmol) at room temperature. After stirring for 10 min, methyl 2-chloro-5-iodonicotinate (J. Org. Chem. 1989, 54, 3618, 594 mg, 2.0 mmol) was added to the reaction mixture. The reaction mixture was stirred under reflux for 16 h. Then the reaction mixture was poured into water (50 mL) and extracted with ether (50 mL×3). The combined organic extracts were washed with brine (50 mL) and dried (sodium sulfate). After removal of the solvent, the residue was purified by flash column chromatography on silica gel (50 g) eluting with hexane/ethyl acetate (2/1) to afford 644 mg (86%) of the title compound: 1H-NMR (CDCl3) δ 8.51 (1H, d, J=2.3 Hz), 8.41 (1H, s), 7.09 (4H, d, J=6.2 Hz), 3.95 (3H, s); MS (ESI) m/z 374 (M+H)+.

1. stirringThe reaction mixture was stirred
2. temperatureunder reflux for 16 h
3. extractionextracted with ether (50 mL×3)
4. washThe combined organic extracts were washed with brine (50 mL)
5. dry with materialdried (sodium sulfate)
6. customAfter removal of the solvent
7. customthe residue was purified by flash column chromatography on silica gel (50 g)
8. washeluting with hexane/ethyl acetate (2/1)