反应详情

Add N-bromosuccinimide (2.46 g, 13.86 mmol) and benzoyl peroxide (0.152 g, 0.630 mmol) to a solution of 2-fluoro-5-methyl-benzoic acid methyl ester (1.06 g, 6.30 mmol) in carbon tetrachloride (50 mL). Heat the mixture at reflux for 4 h. Cool the mixture to room temperature and wash with saturated aqueous sodium bicarbonate solution (10 mL) and brine (10 mL). Dry the organic layer over anhydrous sodium sulfate, filter, and concentrate under reduced pressure. Dissolve the resulting residue in dimethylsulfoxide (30 mL) and heat at reflux for 16 h. Cool the mixture to room temperature and dilute with water (100 mL) and ethyl acetate (100 mL). Extract the aqueous layer with ethyl acetate (3×100 mL). Wash the combined organic layers with water (3×100 mL), followed by brine (100 mL). Dry the organic layer over anhydrous sodium sulfate, filter and concentrate. Purify the residue by chromatography over silica gel, eluting with hexanes/ethyl acetate (80:20), to provide the title compound as a tan solid (0.228 g, 20%). 1H NMR (CDCl3, 300 MHz) δ 3.89 (s, 3H), 7.31-7.44 (m, 1H), 8.05-8.12 (m, 1H), 8.44-8.53 (m, 1H), 10.00 (s, 1H); TLC Rf=0.65 (3:1 Hexanes/Ethyl Acetate).

1. temperatureHeat the mixture
2. temperatureat reflux for 4 h
3. washwash with saturated aqueous sodium bicarbonate solution (10 mL) and brine (10 mL)
4. dry with materialDry the organic layer over anhydrous sodium sulfate
5. filtrationfilter
6. concentrationconcentrate under reduced pressure
7. dissolutionDissolve the resulting residue in dimethylsulfoxide (30 mL)
8. temperatureheat
9. temperatureat reflux for 16 h
10. temperatureCool the mixture to room temperature
11. additiondilute with water (100 mL) and ethyl acetate (100 mL)
12. extractionExtract the aqueous layer with ethyl acetate (3×100 mL)
13. washWash the combined organic layers with water (3×100 mL)
14. dry with materialDry the organic layer over anhydrous sodium sulfate
15. filtrationfilter
16. concentrationconcentrate
17. customPurify the residue by chromatography over silica gel
18. washeluting with hexanes/ethyl acetate (80:20)