In a 250 mL three-neck flask, 2,4-dichloropyrimidine (5.0 g, 33.56 mmol) was dissolved in a solvent mixture of 1,4-dioxane and water (4:1, 50 mL) and pyridine-3-boronic acid (4.95 g, 40.27 mmol), potassium carbonate (9.28 g, 67.12 mmol) and Pd(dppf)Cl2 (2.45 g , 3.36 mmol). The system was displaced three times with argon, gradually heated to 90 °C and reacted for 4 hours. Upon completion of the reaction, the system was concentrated under reduced pressure to remove most of the solvent, ethyl acetate (150 mL) and water (100 mL) were added for extraction and separation, and then the aqueous phase was extracted with ethyl acetate (80 mL). The organic phases were combined and washed with water (80 mL×2) and saturated saline (80 mL×2) sequentially, and the organic phase was dried with anhydrous sodium sulfate for 3 h. The crude product was obtained by filtration and concentration. The crude product was stirred with mixed solvents of petroleum ether and ethyl acetate (6 mL) for 1 h, filtered and dried in vacuum to obtain 4.8 g of 2-chloro-4-(3-pyridinyl)pyrimidine in 74.6% yield with HPLC purity >95%.
