Hydrochloric Acid → HCID 70395308, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 1.0 g of ethyl 3-amino-4,4,4-trifluorocrotonate in 10 ml of absolute toluene is added dropwise while stirring at 0° C. during 15 minutes to a suspension of 0.24 g of a 55% sodium hydride dispersion in 20 ml of absolute dimethylformamide and the mixture is stirred at 0° C. for 15 minutes. The reaction mixture is subsequently cooled to -30° C. and treated with a solution of 1.26 g of 4-chloro-2-fluoro-5-isopropoxyphenyl isocyanate in 10 ml of absolute toluene. The temperature rises rapidly to -10° C. and the reaction mixture is thereafter stirred at room temperature for 2 hours. The reaction mixture is poured into a solution of 3 ml of 2N hydrochloric acid and 500 ml of water and the aqueous mixture is extracted twice with 100 ml of ethyl acetate each time, and the organic phases are washed twice with 50 ml of water each time, dried over anhydrous sodium sulphate and evaporated to dryness under reduced pressure. The residue is recrystallized from diethyl ether/n-hexane. Via ethyl 3-[3-(4-chloro-2-fluoro-5 -isopropoxyphenyl)ureido]-4,4,4-trifluorocrotonate (m.p. 144°-146° C.), which is not isolated, there is obtained 3-(4-chloro-2-fluoro-5-isopropoxyphenyl)-6 -trifluoromethyl-2,4(1H,3H)-pyrimidinedione, m.p. 195°-197° C.

Provenance & Evidence