反应详情

To a mixture of 2-amino-3-hydroxybenzoic acid hydrobromide (0.5 g, 2.14 mmol) and triethylamine (0.90 mL, 6.42 mmol) in dichloromethane (15 mL) was added phenylacetyl chloride (0.28 mL, 2.14 mmol) dropwise, then the reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with dichloromethane, and then washed with 2 N HCl. The aqueous layer was extracted with dichloromethane. The combined organic layers were washed with brine, dried (Na2SO4), filtered and concentrated. The crude product was dissolved in toluene (8 mL) and the solution was treated with p-toluenesulfonic acid monohydrate (537 mg, 2.83 mmol). The reaction mixture was then heated to reflux for 5 h. The reaction was cooled to room temperature, poured into water and extracted with ethyl acetate. The organic layer was separated, then washed with water (3×100 mL), brine, dried (Na2SO4), filtered and concentrated to afford 2-benzylbenzoxazole-4-carboxylic acid (277 mg, 51%) as a white solid: 1H NMR (500 MHz, DMSO-d6) δ 13.08 (br s, 1H), 7.91 (dd, J=7.1, 1.0 Hz, 1H), 7.85 (dd, J=7.7, 1.0 Hz, 1H), 7.44 (t, J=7.9 Hz, 1H), 7.40-7.34 (m, 4H), 7.31-7.27 (m, 1H), 4.40 (s, 2H); MS (ESI+) m/z 254 (M+H).

1. washwashed with 2 N HCl
2. extractionThe aqueous layer was extracted with dichloromethane
3. washThe combined organic layers were washed with brine
4. dry with materialdried (Na2SO4)
5. filtrationfiltered
6. concentrationconcentrated
7. dissolutionThe crude product was dissolved in toluene (8 mL)
8. temperatureThe reaction mixture was then heated
9. temperatureto reflux for 5 h
10. temperatureThe reaction was cooled to room temperature
11. extractionextracted with ethyl acetate
12. customThe organic layer was separated
13. washwashed with water (3×100 mL), brine
14. dry with materialdried (Na2SO4)
15. filtrationfiltered
16. concentrationconcentrated