Synthesis
Example 2: Synthesis of 4,6-dichloro-2-trifluoromethylpyrimidine (Compound V)
Step 2: In a 5L round-bottomed flask equipped with a mechanical stirrer, 4,6-dihydroxy-2-trifluoromethylpyrimidine (VI; 540 g; 3.0 mol) was mixed with phosphorus trichloride (1300 mL; 2147 g; 14.0 mol). Triethylamine (607 g; 6.0 mol) was added slowly over a period of 1 h. Exothermic phenomena were observed during the reaction. Subsequently, the reaction mixture was heated on a dry bath for 3 hours. Upon completion of the reaction, the mixture was cooled to 40°C and then slowly poured into a mixture consisting of 10 kg of ice and 2 kg of water under continuous stirring. The mixture was extracted using dichloromethane (4 x 0.5 L). The organic phases were combined, dried with anhydrous magnesium sulfate and filtered. The filtrate was concentrated under vacuum to give the crude product V. For further purification, the purified product in the form of a colorless liquid was obtained by distillation (steam bath, 48°-50°C/2 mmHg) in 78.8% yield.
Elemental Analysis Results:
Calculated values (C5HCl2F3N2) : C, 27.68; H, 0.47; N, 12.91.
Measured values: C, 27.45; H, 0.39; N, 12.86.
References
[1] Patent: US4963678, 1990, A
[2] Patent: WO2005/95357, 2005, A2. Location in patent: Page/Page column 140; 141
[3] Patent: CN106883185, 2017, A. Location in patent: Paragraph 0018
