Step 1: DIPEA (4 mL, 23.20 mmol) was added dropwise to a solution of acetonitrile (80 mL) containing 5-bromo-2-chloropyrimidine (3.0 g, 15.50 mmol) under nitrogen protection. Subsequently, methyl 4-piperidinecarboxylate (3.321 g, 23.20 mmol) was added to the reaction system. The reaction mixture was stirred at room temperature for 16 hours. After completion of the reaction, the solvent was concentrated to dryness by rotary evaporator. Deionized water and ethyl acetate (EtOAc) were added to quench the reaction and the organic layer was separated. The organic phase was dried over anhydrous sodium sulfate and concentrated again to dryness. The crude product was purified by silica gel column chromatography with an elution gradient of heptane/ethyl acetate (100:0 to 0:100). The fractions containing the target product were collected, combined and concentrated to dryness to give methyl 1-(5-bromopyrimidin-2-yl)piperidine-4-carboxylate (1.84 g, 41% yield) as a white solid.
