反应详情

温度

-30 °C

To a suspension of sodium hydride (60% dispersion in oil, 2.5 g) in anhydrous N,N-dimethylformamide (100 ml) was added dropwise a solution of ethyl-3-amino-4,4,4-trifluorocrotonate in toluene (50 ml) at 0° C. under nitrogen atmosphere. After addition, the mixture was stirred for 20 min at same temperature, then cooled to −30° C. A solution of (4-chloro-2-nitrophenyl)isocyanate in toluene (50 ml) was added dropwise. After stirring for 20 min, the cold bath was removed and the resulting mixture was stirred overnight at ambient temperature. The reaction mixture was partitioned between ethyl acetate and 1N-hydrochloric acid. The organic phase was washed with brine (×2) and dried over anhydrous sodium sulfate. The solvent was removed in vacuo and the residue was purified by column chromatography on silica gel eluted with ethyl acetate and hexane (1:1) to afford 3-(4-chloro-2-nitrophenyl)-6-trifluoromethyl-2,4(1H, 3H)-pyrimidinedione (10.2 g) as a yellow solid.

1. additionAfter addition
2. stirringAfter stirring for 20 min
3. customthe cold bath was removed
4. stirringthe resulting mixture was stirred overnight at ambient temperature
5. customThe reaction mixture was partitioned between ethyl acetate and 1N-hydrochloric acid
6. washThe organic phase was washed with brine (×2)
7. dry with materialdried over anhydrous sodium sulfate
8. customThe solvent was removed in vacuo
9. customthe residue was purified by column chromatography on silica gel
10. washeluted with ethyl acetate and hexane (1:1)