Methyl iodide → 3-[4-(4-Chlorophenylmethoxy)-2-fluorophenyl]-1-methyl-6-trifluoromethyluracil

Participants

Reaction Conditions

Reaction Steps

A stirred mixture of 3.8 grams (0.02 mole) of ethyl 3-amino-4,4,4-trifluoro-2-butenoate and 0.8 gram (0.02 mole) of sodium hydride in 60 mL of tetrahydrofuran was cooled to -20° C., and a solution of 5.5 grams (0.02 mole) of 2-fluoro-4-(4-chlorophenylmethoxy)phenyl isocyanate in 60 mL of tetrahydrofuran was added slowly. Upon completion of addition, the reaction mixture was allowed to warm to ambient temperature. The reaction mixture was then heated to 70° C. where it was stirred for about 18 hours. After this time the reaction mixture was cooled and concentrated under reduced pressure to a solid residue. The residue was slurried in diethyl ether and filtered to collect the solid sodium salt of 3-[4-(4-chlorophenylmethoxy)-2-fluorophenyl]-6-trifluoromethyluracil. The solid sodium salt was then taken up with 2.8 grams (0.2 mole) of potassium carbonate and 5.9 grams (0.04 mole) of methyl iodide in 80 mL of N,N-dimethylformamide, and the stirred mixture was heated at 70° C. for about 7 hours. After this time the reaction mixture was poured into water, and the resultant solid was collected by filtration, yielding, when dried, 4.5 grams of 3-[4-(4-chlorophenylmethoxy)-2-fluorophenyl]-1-methyl-6-trifluoromethyluracil, mp 134°-135° C. The NMR spectrum was consistent with the proposed structure.

Provenance & Evidence