反应详情

温度

35 °C

Additional procedure. Ethyl 3-hydroxy-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxylate (50 g, 0.186 mol) and ethanol SDA3A (500 mL) was added to a 1 L round bottom flask equipped with a mechanical stirrer, nitrogen inlet-outlet, temperature probe, and condenser. Triethylamine (18.86 g, 0.186 mol) was added to the slurry. The resulting solution was heated to 35° C. followed by slow addition of 4-fluorobenzylamine (35.0 g, 0.279 mol). The thick slurry was heated at 78° C. with stirring for 6 h. The reaction mixture was polish filtered and the filtrate reheated to 70° C. The pH was adjusted to about 1.0 by slow addition of 1N HCl (405 mL). The thick slurry was cooled to 20–25° C., the solids filtered off, washed twice with ethanol SDA 3A (each 250 mL) and twice with water (each 500 mL). The white solid was dried in vacuo at 50–55° C. to afford N-[(4-fluorophenyl)methyl]-4,6,7,9-tetrahydro-3-hydroxy-9,9-dimethyl-4-oxo-pyrimido[2,1-c][1,4]oxazine-2-carboxamide (58.9 g).

1. customequipped with a mechanical stirrer, nitrogen inlet-outlet
2. temperatureThe thick slurry was heated at 78° C.
3. filtrationfiltered
4. customreheated to 70° C
5. additionThe pH was adjusted to about 1.0 by slow addition of 1N HCl (405 mL)
6. temperatureThe thick slurry was cooled to 20–25° C.
7. filtrationthe solids filtered off
8. washwashed twice with ethanol SDA 3A (each 250 mL) and twice with water (each 500 mL)
9. customThe white solid was dried in vacuo at 50–55° C.