Chloroacetyl chloride → 7-Methyl-2H-1,4-benzoxazin-3(4H)-one

Participants

Reaction Steps

To a mixture of 2-amino-5-methyl-phenol (Alfa, 15.0 g, 122 mmol), K2CO3 (50.5 g, 365 mmol) and Bu4NBr (3.94 g, 12.18 mmol) in acetonitrile (400 mL) at 0° C. was added 2-chloroacetyl chloride (15.1 g, 10.0 mL, 134 mmol) drop-wise. After addition, the mixture was heated at reflux for 2.5 h. The reaction mixture was cooled to ambient temperature and evaporated in vacuo. Water was added (500 mL) and the aqueous solution was extracted with EtOAc (3×150 mL). The combined organic phase was washed with brine (100 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 25% EtOAc in petroleum ether) to give 7-methyl-4H-benzo[1,4]oxazin-3-one as a brown solid (14.1 g, 71%). 1H NMR (DMSO-d6, 400 MHz): δ 10.58 (s, 1H), 6.76 (m, 3H), 4.52 (s, 2H), 2.21 (s, 3H).

Provenance & Evidence