反应详情

温度

5 °C

In a 1000 mL-volume glass flask equipped with a stirrer, a thermometer and a reflux condenser were placed 50.0 g (172 mmol.) of 4-(4-fluorophenyl)-2-hydroxy-6-isopropyl-5-methoxycarbonylpyrimidine, 20.8 g (189 mmol.) of sodium t-pentoxide, and 344 mL of acetonitrile, and the resulting mixture was stirred at 0-10° C. for 30 minutes. To the mixture was slowly added 36.1 g (189 mmol.) of p-toluenesulfonyl chloride, and the reaction was carried out at for 5 hours at room temperature. Subsequently, the reaction mixture was cooled to a temperature of 0-10° C. To the cooled reaction mixture were added 28.2 g (258 mmol.) of N-methylmethanesulfonamide and 26.5 g (241 mmol.) of sodium t-pentoxide. The mixture was kept at 0-10° C. for one hour and then heated to 75-82° C. for 2 hours under refluxing, to carry out a reaction. After the reaction was complete, the mixture was cooled to room temperature. To the cooled mixture was added 344 mL of water. The aqueous mixture was cooled to 0-10° C. and stirred for one hour, precipitating a crystalline product. The crystalline product was collected by filtration and dried, to obtain 45.3 g of 4-(4-fluorophenyl)-6-isopropyl-5-methoxycarbonyl-2-(N-methyl-N-methanesulfonylamino)pyrimidine as a pale yellow crystalline product. The yield was 68% (based on the amount of 4-(4-fluorophenyl)-2-hydroxy-6-isopropyl-5-methoxycarbonylpyrimidine).

1. customIn a 1000 mL-volume glass flask equipped with a stirrer
2. customwas carried out at for 5 hours at room temperature
3. temperatureSubsequently, the reaction mixture was cooled to a temperature of 0-10° C
4. customTo the cooled reaction mixture
5. waitThe mixture was kept at 0-10° C. for one hour
6. temperatureheated to 75-82° C. for 2 hours
7. temperatureunder refluxing
8. customa reaction
9. temperaturethe mixture was cooled to room temperature
10. temperatureThe aqueous mixture was cooled to 0-10° C.
11. stirringstirred for one hour
12. customprecipitating a crystalline product
13. filtrationThe crystalline product was collected by filtration
14. customdried