反应详情

温度

-20 °C

A mixture of 0.40 g (0.01 0 mole) of sodium hydride and 1.83 g (0.10 mole) of ethyl 3-amino-4,4,4-trifluorocrotonate was cooled to -20° C. To this mixture was slowly added 2.23 g (0.01 mole) of 4-chloro-2,3-dihydro-2,2-dimethylbenzofuran-7-yl isocyanate. Upon completion of addition, the reaction mixture was allowed to warm to ambient temperature at which it was stirred for one hour. At the conclusion of this period the reaction mixture was heated to 85° C. at which it was stirred for approximately 16 hours. Then 1.38 g (0.01 mole) of potassium carbonate and 2.80 g (0.020 mole) of methyl iodide were added to the reaction mixture, and it was heated at 75° C. for seven hours. At the conclusion of this period the mixture was filtered, and the filtrate diluted with 200 mL of water. This mixture was extracted with diethyl ether. The extracts were dried over anhydrous magnesium sulfate, filtered, and the solvent evaporated from the filtrate under reduced pressure, leaving a yellow oil as residue. This oil was passed through a column of silica gel, eluting with methylene chloride:heptane (70:30). Product-containing fractions were combined, and the solvent was evaporated under reduced pressure, leaving a solid residue. This residue was washed with petroleum ether, yielding 1.50 g of 3-(4-chloro-2,3-dihydro-2,2-dimethylbenzofuran-7-yl)-1-methyl-6-trifluoromethyluracil (Compound 3), m.p. 152°-153° C. The NMR spectrum was consistent with the proposed structure.

1. additionUpon completion of addition
2. temperatureto warm to ambient temperature at which it
3. temperatureAt the conclusion of this period the reaction mixture was heated to 85° C. at which it
4. stirringwas stirred for approximately 16 hours
5. temperaturewas heated at 75° C. for seven hours
6. filtrationAt the conclusion of this period the mixture was filtered
7. additionthe filtrate diluted with 200 mL of water
8. extractionThis mixture was extracted with diethyl ether
9. dry with materialThe extracts were dried over anhydrous magnesium sulfate
10. filtrationfiltered
11. customthe solvent evaporated from the filtrate under reduced pressure
12. customleaving a yellow oil as residue
13. washeluting with methylene chloride:heptane (70:30)
14. customthe solvent was evaporated under reduced pressure
15. customleaving a solid residue
16. washThis residue was washed with petroleum ether