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

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).

1. additionAfter addition
2. temperaturethe mixture was heated
3. temperatureat reflux for 2.5 h
4. customevaporated in vacuo
5. additionWater was added (500 mL)
6. extractionthe aqueous solution was extracted with EtOAc (3×150 mL)
7. washThe combined organic phase was washed with brine (100 mL)
8. dry with materialdried over anhydrous Na2SO4
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customThe residue was purified by column chromatography on silica gel (eluting with 25% EtOAc in petroleum ether)

ORD record

ord-5e4a6fb433c54010a6b23b2d5bc24de3

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09115151B2