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

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Reaction Steps

To a solution of the crude 2-(6-acetoxy-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester in THF (80 mL) was added morpholine (5.5 mL, 63 mmol) and the mixture was heated to reflux overnight. The reaction mixture was cooled to ambient temperature and diluted with EtOAc (100 mL). The mixture was washed with brine (30 mL) and the combined organic phase was dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatograph on silica gel (eluting with 10% EtOAc in petroleum ether) to give 2-(6-hydroxy-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester as a white solid (3.2 g, 57% over two steps). 1H NMR (CDCl3, 400 MHz): δ 6.88 (d, J=8.8 Hz, 1H), 6.47 (dd, J=2.8 Hz, J=8.8 Hz, 1H), 6.39 (d, J=2.8 Hz, 1H), 5.24 (q, J=6.8 Hz, 1H), 4.54 (d, J=14.8 Hz, 2H), 4.20 (q, J=7.2 Hz, 2H), 1.62 (d, J=6.8 Hz, 3H), 1.21 (t, J=7.2 Hz, 3H). The phenol OH was not observed in CDCl3.

Provenance & Evidence