反应详情

A solution of phenylmethyl 2-[(4-hydroxy-3-nitrophenyl)carbonyl]benzoate (5.78 g, 15.3 mmol) in acetic acid (50 mL) was treated with iron powder (8.5 g, 153 mmol) at 50° C. for 30 min. After cooling to rt, the mixture was diluted with ethyl acetate, and the solids were removed by filtration though celite. The organic filtrate was washed with saturated sodium bicarbonate, which lead to further precipitation of solid contaminants. These solids were removed by filtration. The resulting organic filtrate was dried over magnesium sulfate, filtered, and concentrated to a brown foam. This material was taken up in DMF (30 mL). To this solution was added ethoxycarbonyl isothiocyanate (2.6 mL, 23 mmol). After stirring for 35 min, EDC (4.4 g, 23 mmol) was added to the reaction mixture. The mixture was stirred at rt for 35 min and then was stirred for a further 1 h at 65° C., and then it was cooled to rt. To the mixture was added 10% aqueous citric acid, and the resulting aqueous mixture was extracted twice with ethyl acetate. The organic extracts were combined, washed with brine, dried over magnesium sulfate, filtered, and concentrated to a brown solid. Contaminants were removed by trituration with methanol. Desired phenylmethyl 2-[(2-{[(ethyloxy)carbonyl]amino}-1,3-benzoxazol-5-yl)carbonyl]benzoate was isolated as a white solid (637 mg, 1.4 mmol, 9.4% yield). A sample was further purified by reverse phase HPLC. 1H NMR (400 MHz, CDCl3): 10.91 (br s, 1H), 8.12 (m 1H), 7.95 (br s, 1H), 7.67 (m, 1H), 7.63-7.52 (m, 3H), 7.47-7.38 (m, 2H), 7.26-7.13 (m, 5H), 5.08 (s, 2H), 4.29 (q, 2H), 1.38 (t, 3H); MS (EI) for C25H20N2O6: 445 (MH+).

1. customthe solids were removed by filtration though celite
2. washThe organic filtrate was washed with saturated sodium bicarbonate, which
3. customlead to further precipitation of solid contaminants
4. customThese solids were removed by filtration
5. dry with materialThe resulting organic filtrate was dried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated to a brown foam
8. stirringThe mixture was stirred at rt for 35 min
9. stirringwas stirred for a further 1 h at 65° C.
10. temperatureit was cooled to rt
11. extractionthe resulting aqueous mixture was extracted twice with ethyl acetate
12. washwashed with brine
13. dry with materialdried over magnesium sulfate
14. filtrationfiltered
15. concentrationconcentrated to a brown solid
16. customContaminants were removed by trituration with methanol