反应详情

To a mixture of 2-amino-3-hydroxybenzoic acid hydrobromide (0.30 g, 1.28 mmol) and pivaloyl chloride (0.16 mL, 1.28 mmol) in dichloromethane (10 mL) was added triethylamine (0.72 mL, 5.12 mmol) dropwise, then the reaction mixture was stirred at room temperature for 1 h. 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 (10 mL) and the solution was treated with p-toluenesulfonic acid monohydrate (240 mg, 1.26 mmol). The reaction mixture was then heated to reflux for 1.5 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, brine, dried (Na2SO4), filtered and concentrated. The crude product was purified by column chromatography (silica gel, 9:1 to 3:1 ethyl acetate/methanol) to afford 2-tert-butylbenzoxazole-4-carboxylic acid (0.15 g, 53%) as a white solid: 1H NMR (300 MHz, DMSO-d6) δ 7.75-7.71 (m, 2H), 7.33 (t, J=7.8 Hz, 1H), 1.45 (s, 9H); MS (ESI+) m/z 220 (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 (10 mL)
8. temperatureThe reaction mixture was then heated
9. temperatureto reflux for 1.5 h
10. temperatureThe reaction was cooled to room temperature
11. extractionextracted with ethyl acetate
12. customThe organic layer was separated
13. washthen washed with water, brine
14. dry with materialdried (Na2SO4)
15. filtrationfiltered
16. concentrationconcentrated
17. customThe crude product was purified by column chromatography (silica gel, 9:1 to 3:1 ethyl acetate/methanol)