反应详情

To a solution of ethyl 2-(7-chloro-1,2,3,4-tetrahydro-2,4-dioxoquinazolin-1-yl)acetate (176 g) in N,N-dimethylformamide (3.5 l) was added sodium hydride (60% in mineral oil, 32.3 g) at 0° C. and the mixture was stirred at room temperature for 4 hours. To the reaction mixture was added a solution of 4-bromo-2-fluorobenzyl bromide (200 g) in N,N-dimethylformamide (100 ml) below 20° C. over a 20-minute period and the resulting mixture was stirred at room temperature for 1 hour. 3N Aqueous hydrochloric acid (62.2 ml) was added to the mixture below 15° C. and the solvent was evaporated in vacuo. The residue was poured into a mixture of ethyl acetate (3 l) and water (3 l), and the resulting mixture was stirred for 15 minutes. The precipitates were filtered off and the organic layer was separated. The solution was washed with brine, dried over magnesium sulfate and evaporated in vacuo. The residue was crystallized with addition of isopropyl ether and the crystals were collected by filtration and washed with isopropyl ether. The crude crystals and the precipitates were mixed and recrystallized from a mixture of ether acetate (0.9 l) and n-hexane (0.9 l) to give ethyl 2-[3-(4-bromo-2-fluorobenzyl)-7-chloro-1,2,3,4-tetrahydro-2,4-dioxoquinazolin-1-yl]acetate (251 g).

1. stirringthe resulting mixture was stirred at room temperature for 1 hour
2. customthe solvent was evaporated in vacuo
3. additionThe residue was poured into a mixture of ethyl acetate (3 l) and water (3 l)
4. stirringthe resulting mixture was stirred for 15 minutes
5. filtrationThe precipitates were filtered off
6. customthe organic layer was separated
7. washThe solution was washed with brine
8. dry with materialdried over magnesium sulfate
9. customevaporated in vacuo
10. customThe residue was crystallized with addition of isopropyl ether
11. filtrationthe crystals were collected by filtration
12. washwashed with isopropyl ether
13. additionThe crude crystals and the precipitates were mixed
14. customrecrystallized from a mixture of ether acetate (0.9 l) and n-hexane (0.9 l)