反应详情

Phenylmagnesium bromide (3.11 mL, 3.0 M in ether, 9.34 mmol) was added at room temperature to a solution of 8-chloro-2-methyl-4H-3,1-benzoxazin-4-one (2.15 g, 10.9 mmol) in benzene (10 mL) and tetrahydrofuran (3 mL). The reaction was refluxed for 2h, cooled, and quenched with 2N hydrochloric acid (10 mL). The layers were separated and the organic phase washed with 5% sodium hydroxide, dried over magnesium sulfate, and concentrated. The residue was refluxed in ethanol (12 mL) and 6N hydrochloric acid (6 mL) overnight, then concentrated in vacuo. The residue was dissolved in benzene (30 mL) and treated with 5N ammonium hydroxide (20 mL). The organic extract was dried and concentrated. The crude product was purified by chromatography (silica gel, 0 to 5% ethyl acetate in hexane gradient elution), giving the title compound (0.84 g). 1H NMR (500 MHz, CDCl3) δ 7.63 (d, J=7 Hz, 2H), 7.54 (t, J=7 Hz, 1H), 7.49–7.42 (m, 3H), 7.39 (d, J=8 Hz, 1H), 6.56 (t, J=8 Hz, 1H), 6.58 (br s, 2H).

1. temperaturecooled
2. customquenched with 2N hydrochloric acid (10 mL)
3. customThe layers were separated
4. washthe organic phase washed with 5% sodium hydroxide
5. dry with materialdried over magnesium sulfate
6. concentrationconcentrated
7. temperatureThe residue was refluxed in ethanol (12 mL)
8. concentration6N hydrochloric acid (6 mL) overnight, then concentrated in vacuo
9. dissolutionThe residue was dissolved in benzene (30 mL)
10. additiontreated with 5N ammonium hydroxide (20 mL)
11. extractionThe organic extract
12. customwas dried
13. concentrationconcentrated
14. customThe crude product was purified by chromatography (silica gel, 0 to 5% ethyl acetate in hexane gradient elution)