54-20-6

3932-97-6

The general procedure for the synthesis of 2,4-dichloro-5-trifluoromethylpyrimidine from 5-trifluoromethyluracil is as follows: 1. 5-Trifluoromethyluracil (250 g, 1.39 mol) and phosphorus trichloride (655 mL, 6.94 mol, 5 eq.) were added to a 3L four-neck flask fitted with an overhead stirrer, a reflux condenser, a dosing funnel, and an internal thermocouple under nitrogen protection. 2. concentrated phosphoric acid (85 wt%, 9.5 mL, 0.1 eq.) was added to the reaction mixture in a single addition and a moderate exothermic phenomenon was observed. 3. Diisopropylethylamine (245 mL, 1.39 mol, 1 eq.) was added slowly dropwise over 15 minutes, controlling the dropwise acceleration so that the internal temperature of the reaction reached 85-90 °C at the end of the dropwise acceleration. Upon completion of the dropwise addition, the reaction mixture changed to a homogeneous light orange solution. 4. The reaction mixture was heated to 100 °C and held for 20 hours until HPLC analysis showed complete consumption of the feedstock. 5. The heating was stopped and the reaction mixture was cooled to 40 °C and then slowly added dropwise to a pre-cooled mixture of 3N HCl (5 L, 10 eq.) and ether (2 L), maintaining the temperature of the quench tank. 6. Separate the organic and aqueous layers, the aqueous layer being extracted once with ether (1 L). The organic layers were combined and washed with water until the washings were neutral (5 times, 1.5 L each), then dried over MgSO4 and concentrated to give 288 g (95% yield) of a light yellow-orange oily product with 96% HPLC purity. 7. The product can be extracted under reduced pressure from aqueous solution of 1.5 L of ether (2 L). 7. The product was further purified by reduced pressure distillation (boiling point 109 °C, 79 mmHg).