反应详情

温度

100 °C

A mixture of ethyl 6-(3-chloro-4-fluorobenzyl)-4-hydroxy-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxylate (22 g, 58 mmol), glacial acetic acid (500 mL), and hydrogen peroxide (65.8 mL, 30% by weight in water) was heated at 100° C. for four hours. The resultant solution was cooled in an ice bath to 25° C. and treated with saturated aqueous sodium sulfite solution while keeping the reaction mixture below 40° C. When starch paper test showed complete consumption of residual peroxide, the solution was concentrated to two third of its volume, pH was adjusted to ˜3 with aqueous HCl and the solution was extracted with dichloromethane (3 times). The organic extracts were combined, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum to afford the title product as oil. 1H NMR (400 MHz, CDCl3) δ 12.65 (s, 1H), 7.9 (s, 1H), 7.38 (dd, J=2, 7 Hz, 1H), 7.27-7.1 (m, 2H), 4.66 (s, 2H), 4.44 (q, J=7 Hz, 2H), 3.52 (t, J=7 Hz, 2H), 2.90 (t, J=7 Hz, 2H), 1.38 (t, J=7 Hz, 3H). ES MS M+1=395.0

1. customthe reaction mixture below 40° C
2. customconsumption of residual peroxide
3. concentrationthe solution was concentrated to two third of its volume
4. extractionthe solution was extracted with dichloromethane (3 times)
5. dry with materialdried over anhydrous sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated under vacuum