反应详情

A stirred solution of 211.0 grams (0.619 mole) of 3-(4-chloro-2,6-difluorophenyl)-1-methyl-6-trifluoromethyl-2,4(1H,3H)-pyrimidinedione in 600 mL of concentrated sulfuric acid was cooled to less than 10° C., and 44 mL (0.689 mole) of aqueous 70% nitric acid was added dropwise at a rate to maintain the reaction temperature below 10° C. Upon completion of addition, the reaction mixture was analyzed by GC, which indicated the reaction was incomplete. The reaction was allowed to warm to ambient temperature and an additional 5 mL (0.078 mole) of aqueous 70% nitric acid was added. The reaction mixture was again analyzed by GC, which indicated the reaction was complete. The reaction mixture was poured into ice-water. The resulting solid was collected by filtration, washed with water, and then taken up in 600 mL of methylene chloride. The resulting solution was washed with two 600 mL portions of water, one 600 mL portion of an aqueous saturated sodium bicarbonate solution, and one 600 mL portion of an aqueous saturated sodium chloride solution. The organic layer was separated, dried with magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure, yielding a waxy tan solid. The solid was triturated with heptane and allowed to stand for about 72 hours. At the conclusion of this period, the solid was collected by filtration, washed with heptane, and dried under reduced pressure, yielding 201.4 grams of title compound. The NMR spectrum was consistent with the proposed structure.

1. temperatureto maintain the reaction temperature below 10° C
2. additionUpon completion of addition
3. filtrationThe resulting solid was collected by filtration
4. washwashed with water
5. washThe resulting solution was washed with two 600 mL portions of water, one 600 mL portion of an aqueous saturated sodium bicarbonate solution, and one 600 mL portion of an aqueous saturated sodium chloride solution
6. customThe organic layer was separated
7. dry with materialdried with magnesium sulfate
8. filtrationfiltered
9. concentrationThe filtrate was concentrated under reduced pressure
10. customyielding a waxy tan solid
11. customThe solid was triturated with heptane
12. filtrationAt the conclusion of this period, the solid was collected by filtration
13. washwashed with heptane
14. customdried under reduced pressure