反应详情

温度

0 °C

A solution of 4.67 g of ethyl 3-amino-4,4,4-trifluorocrotonate in 15 ml of toluene is added dropwise while stirring at 0° C. during 20 minutes to a suspension of 1.11 g of a 55% sodium hydride dispersion in 30 ml of absolute dimethylformamide, and the mixture is stirred at 0° C. for 15 minutes. The reaction mixture is subsequently cooled to -40° C. and a solution of 6.24 g of 2-chloro-4-fluoro-5-isocyanatophenyl methyl carbonate in 30 ml of toluene is added dropwise during 5 minutes. The reaction mixture is stirred at room temperature for 1 hour and stirred for a further 30 minutes with a solution of 5.40 g of sodium carbonate in 100 ml of water. The aqueous phase is separated. extracted twice with 50 ml of diethyl ether each time and adjusted to pH 1 with 8 ml of 2N hydrochloric acid. The mixture is extracted twice with 100 ml of diethyl ether each time and the organic phases are washed with water. dried over anhydrous sodium sulphate and evaporated to dryness under reduced pressure. The residue is recrystallized from diethyl ether/n-hexane. There is obtained 3-(4-chloro-2-fluoro-5-hydroxyphenyl)-6-trifluoromethyl-2,4(1H,3H)-pyrimidinedione, m.p. 223°-225° C.

1. temperatureThe reaction mixture is subsequently cooled to -40° C.
2. stirringThe reaction mixture is stirred at room temperature for 1 hour
3. customThe aqueous phase is separated
4. extractionextracted twice with 50 ml of diethyl ether each time
5. extractionThe mixture is extracted twice with 100 ml of diethyl ether each time
6. washthe organic phases are washed with water
7. dry with materialdried over anhydrous sodium sulphate
8. customevaporated to dryness under reduced pressure
9. customThe residue is recrystallized from diethyl ether/n-hexane