Potassium Carbonate → 2-(6-Nitro-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

A suspension of 6-nitro-4H-benzo[1,4]oxazin-3-one (135.0 g, 700 mmol) and K2CO3 (289.8 g, 2100 mmol) in DMF (1.5 L) was stirred at 70° C. for 0.5 h and then 2-bromo-propionic acid ethyl ester (136.3 mL, 1050 mmol) was added to the mixture. The reaction mixture was heated at 80° C. for 2 h then cooled to ambient temperature. The solvent was removed in vacuo and the residue was dissolved in water (600 mL) and extracted with EtOAc (3×200 mL). The combined organic layer was concentrated, washed with brine (3×30 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo to give the crude product, which was purified by chromatography on silica gel (eluting with 20% EtOAc in petroleum ether) to give 2-(6-nitro-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester as a brown liquid (185.0 g, 90%). 1H NMR (CDCl3, 400 MHz): δ 7.90 (dd, J=2.4 Hz, J=9.2 Hz, 1H), 7.72 (d, J=2.4 Hz, 1H), 7.06 (d, J=9.2 Hz, 1H), 5.27 (q, J=7.2 Hz, 1H), 4.67 (d, J=15.2 Hz, 2H), 4.18 (m, 2H), 1.62 (d, J=7.2 Hz, 3H), 1.18 (t, J=7.2 Hz, 3H).

Provenance & Evidence