24522-30-3

455-14-1

372-09-8

24522-30-3

In 700 L of tetrahydrofuran, 63.4 kg of cyanoacetic acid was dissolved and stirred at room temperature and under nitrogen protection. The resulting solution was cooled to 0 to 10°C, followed by slow dropwise addition of N-methylmorpholine at the same temperature over about 1 hour. Next, 100.0 kg of 4-trifluoromethylaniline was added dropwise. Continuing at the same temperature, 91.3 kg of isopropyl chlorocarbonate was slowly added dropwise to the reaction mixture over about 1 hour. After the dropwise addition was completed, the reaction was continued with stirring for 1 to 2 hours. After completion of the reaction, 200 L of water was added to the reaction mixture, stirred and left to stratify. The organic layer (upper layer) was washed with 16.7% brine, followed by the addition of 400 L of isopropanol and concentrated under reduced pressure until the volume of liquid was reduced to 400 L. 400 L of isopropanol was added again, and the concentration was repeated under reduced pressure until the volume of liquid was 400 L. 100 L of isopropanol was added to the concentrated solution at 20 to 30 °C followed by a slow dropwise addition of 500 L of water at about 20 °C. The reaction was completed with the addition of 500 L of water. After completion of the dropwise addition, stirring was continued for 1 hour at the same temperature. The mixture was cooled to 0 to 10°C and stirred at that temperature for 1 hour. The precipitated crystals were collected by filtration and dried to give 134.5 kg of 2-cyano-N-(4-(trifluoromethyl)phenyl)acetamide (IV) in 95.0% yield.