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A stirred solution of 11.8 grams (0.039 mole) of 3-(4-amino-2-fluorophenyl)-1-methyl-6-trifluoromethyluracil and 25 mL of concentrated hydrochloric acid in 130 mL of acetone was cooled to below 10° C., and a solution of 2.7 grams (0.039 mole) of sodium nitrite in 10 mL of water was added dropwise. Upon completion of addition, the reaction mixture was stirred at below 10° C. for one hour. After this time 0.3 gram (0.003 mole) of copper(I) chloride was added in one portion. The reaction mixture was then cooled to 0° C., and 33.5 grams (0.390 mole) of methyl 2-propenoate was added slowly, portion-wise. The addition caused an exothermic reaction, which raised the reaction mixture temperature to about 15° C. Upon completion of addition, the reaction mixture was allowed to warm to ambient temperature, where it was stirred for about 16 hours. The reaction mixture was then poured into water, and the mixture was extracted with diethyl ether. The ether extract was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residue. The residue was subjected to column chromatography on silica gel. Elution was accomplished using 1:1 heptane-methylene chloride and methylene chloride. The product-containing fractions were combined and concentrated under reduced pressure, yielding 10.4 grams of methyl 2-chloro-3-[3-fluoro-4-(1-methyl-6-trifluoromethyl-2,4(1H,3H)-pyrimidinedion-3-yl)phenyl]propanoate, mp 101°-103° C. The NMR spectrum was consistent with the proposed structure.

1. additionUpon completion of addition
2. additionThe addition
3. customan exothermic reaction, which
4. temperatureraised the reaction mixture temperature to about 15° C
5. additionUpon completion of addition
6. temperatureto warm to ambient temperature
7. stirringwhere it was stirred for about 16 hours
8. extractionthe mixture was extracted with diethyl ether
9. extractionThe ether extract
10. dry with materialwas dried with magnesium sulfate
11. filtrationfiltered
12. concentrationThe filtrate was concentrated under reduced pressure to a residue
13. washElution
14. concentrationconcentrated under reduced pressure