反应详情

Thionyl chloride (5.88 g, 49.4 mmol) was added dropwise to anhydrous methanol (45 mL) at 5° C. The mixture was stirred at this temperature for 30 min. Then 5-fluoro-2-hydroxy-3-nitrobenzoic acid was added to the mixture and the resulting mixture was heated to reflux for 24 hr. Solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate (100 mL), washed with water (100 mL×3), brine (50 mL), dried over anhydrous sodium sulfate and concentrated to give crude product. The crude product was purified by chromatography (silica gel, petroleum ether/ethyl acetate=100:1 to 5:1) to give methyl 5-fluoro-2-hydroxy-3-nitrobenzoate (3.4 g, yield 80% for two steps). 1H-NMR (400 MHz, CDCl3-d) δ 4.04 (s, 3H), 7.88-7.90 (dd, J1=7.6 Hz, J2=3.2 Hz, 1H), 7.93-7.96 (dd, J1=7.6 Hz, J2=3.2 Hz, 1H), 11.74 (s, 1H); LC-MS (ESI) m/z 216 [M+1]+.

1. temperaturethe resulting mixture was heated
2. temperatureto reflux for 24 hr
3. customSolvent was removed under reduced pressure
4. dissolutionThe residue was dissolved in ethyl acetate (100 mL)
5. washwashed with water (100 mL×3), brine (50 mL)
6. dry with materialdried over anhydrous sodium sulfate
7. concentrationconcentrated
8. customto give crude product
9. customThe crude product was purified by chromatography (silica gel, petroleum ether/ethyl acetate=100:1 to 5:1)