反应详情

To a mixed suspension of 7-chloro-2,4-dioxo-1,2,3,4-tetrahydroquinazoline (20 g) and hexamethyldisilazane (16.42 g) in toluene (60 ml) was added sulfuric acid (0.80 g) dropwise and the silylation reaction was carried out at an internal temperature of 110˜120° C. for 6 hours. After completion of silylation, the toluene was distilled off to recover a concentrate containing 7-chloro-2,4-bis(trimethylsilyloxy)quinazoline. To this concentrate were added propylene carbonate (40 ml), ethyl chloroacetate (13.72 g) and ethyl bromoacetate (3.40 g), and the reaction was carried out at an internal temperature of 125˜140° C. for 6 hours. After completion of reaction, the reaction mixture was cooled to an internal temperature of ≦70° C. and ethyl acetate (80 ml) was added. Then, methanol (60 ml) was added dropwise over 30 minuets. After completion of dropwise addition, the mixture was cooled to ≦20° C. and stirred for 1 hour. The resulting crystal crop was harvested by filtration, washed serially with methanol (40 ml) and water (100 ml) and dried to provide ethyl 2-(7-chloro-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-1-yl)acetate (28.16 g) as white crystals.

1. customthe silylation reaction
2. distillationAfter completion of silylation, the toluene was distilled off
3. customto recover a concentrate
4. additioncontaining 7-chloro-2,4-bis(trimethylsilyloxy)quinazoline
5. additionTo this concentrate were added propylene carbonate (40 ml), ethyl chloroacetate (13.72 g) and ethyl bromoacetate (3.40 g)
6. waitthe reaction was carried out at an internal temperature of 125˜140° C. for 6 hours
7. customAfter completion of reaction
8. additionwas added
9. additionAfter completion of dropwise addition
10. temperaturethe mixture was cooled to ≦20° C.
11. filtrationThe resulting crystal crop was harvested by filtration
12. washwashed serially with methanol (40 ml) and water (100 ml)
13. customdried