1,2-Dichloroethane → Phenylmethyl 2-[(2-{[(ethyloxy)carbonyl]amino}-1,3-benzoxazol-5-yl)carbonyl]benzoate

Participants

Reaction Steps

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+).

Provenance & Evidence