General synthesis of (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazole and compound (CAS:1421920-40-2) as raw material for (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-1-(3,3-difluoroazetidin-1-yl)prop-2-en-1-one Procedure: to a 50 mL three-necked round-bottomed flask fitted with a nitrogen inlet under nitrogen protection was added 3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazole (0.18 g, 1.0 eq.) dissolved in DMF (5.0 mL, 27.0 V), followed by the addition of DABCO (0.143 g, 2.0 eq.) and (Z)-1-(3, 3-difluoroazetidin-1-yl)-3-iodo-2-en-1-one (0.192 g, 1.1 eq.). The reaction mixture was stirred at room temperature for 2-3 hours. The reaction progress was monitored by TLC using 80% ethyl acetate-hexane as the mobile phase with an Rf value of 0.60 for the feedstock and 0.4 for the product.Upon completion of the reaction, the mixture was poured into ice water (50 mL) and extracted with EtOAc (3 x 25 mL). The organic layers were combined, washed with brine solution (3 × 25 mL), dried over MgSO4, filtered, and concentrated by rotary evaporation (25 °C, 20 mmHg) to give 0.3 g of crude product. The crude product was purified by silica gel column chromatography (60/120 mesh) using ethyl acetate:hexane as mobile phase. The silica gel column (5 × 10 cm) was packed with hexane and then eluted with ethyl acetate in a gradient manner, starting from 40% ethyl acetate/hexane and gradually increasing to 45% ethyl acetate/hexane, and 50 mL of gradient was collected. The target compound was eluted starting from 40% ethyl acetate/hexane. The TLC distribution grade fractions containing the target compound were combined, resulting in 70 mg of pure product in 25.64% yield.
