反应详情

温度

80 °C

To a solution of (2R,3S)-2-(2,4-difluorophenyl)-3-methyl-2-[(1H-1,2,4-triazol-1-yl)methyl]oxirane (2.46 g, 9.8 mmol, obtained as described in Tasaka et al., Chem.Pharm.Bull. 1993, 41, 1035-1042) in N-methylpyrrolidone (10 mL), 7-chloro-3H-quinazolin-4-one (1.77 g, 9.8 mol) and K2CO3 (1.35 g, 9.8 mmol) were added. The resulting solution was heated at 80° C. for 3 days. The mixture was cooled to room temperature, water was then added and the pH was adjusted to 7. The mixture was extracted with ethyl acetate (4×). The combined organic extracts were washed with water (4×), dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated to a reduced volume and was allowed to crystallize at 0° C. The resulting product was filtered, dried and dissolved in hot ethanol (10 mL/g). The insoluble material was filtered off, and the filtrate was then poured over cold water (120 mL/g of UR-9825) under stirring. The resulting precipitate was filtered and dried in vacuo (50° C.) to give the desired product as a white amorphous powder (3.1 g, 75%).

1. temperatureThe mixture was cooled to room temperature
2. extractionThe mixture was extracted with ethyl acetate (4×)
3. washThe combined organic extracts were washed with water (4×)
4. dry with materialdried over anhydrous Na2SO4
5. filtrationfiltered
6. concentrationThe filtrate was concentrated to a reduced volume
7. customto crystallize at 0° C
8. filtrationThe resulting product was filtered
9. customdried
10. dissolutiondissolved in hot ethanol (10 mL/g)
11. filtrationThe insoluble material was filtered off
12. additionthe filtrate was then poured over cold water (120 mL/g of UR-9825)
13. filtrationThe resulting precipitate was filtered
14. customdried in vacuo (50° C.)