反应详情

温度

0 °C

To a cooled (0° C.) solution of 7-amino-4-methyl-2H-1,4-benzoxazin-3(4H)-one (10.0 g, 56 mmol) in water (80 mL) was added concentrated sulfuric acid (17 mL). After stirring at 0° C. for 10 min, a solution of sodium nitrite (4.1 g, 59 mmol) in water (10 mL) was added dropwise. After stirring for 0.5 h, the reaction mixture was added dropwise to a solution of cupric sulfate (50 g) in water (300 mL) at reflux. Once the addition was complete, the reaction mixture was allowed to cool to ambient temperature and was extracted with ethyl acetate (5×200 mL). The combined organic solution was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by trituration with ice-cold ethyl acetate (25 mL) and the solid was collected by vacuum filtration, air-dried and dried under high vacuum to afford 7-hydroxy-4-methyl-2H-1,4-benzoxazin-3(4H)-one (3.22 g, 32%) as a tan solid: 1H NMR (300 MHz, DMSO-d6) δ9.40 (s, 1H), 6.95 (d, J=8.7 Hz, 1H), 6.45 (dd, J=8.7, 2.6 Hz, 1H), 6.40 (d, J=2.6 Hz, 1H), 4.56 (s, 2H), 3.21 (s, 3H); MS (ES+) m/z 180.1 (M+1).

1. stirringAfter stirring for 0.5 h
2. temperatureat reflux
3. additionOnce the addition
4. temperatureto cool to ambient temperature
5. extractionwas extracted with ethyl acetate (5×200 mL)
6. dry with materialThe combined organic solution was dried over anhydrous sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe residue was purified by trituration with ice-cold ethyl acetate (25 mL)
10. filtrationthe solid was collected by vacuum filtration
11. customair-dried
12. customdried under high vacuum