Under nitrogen protection, 300 g of anhydrous tetrahydrofuran was added to the reaction flask with stirring turned on, followed by the addition of 17 g of 2-methoxy-5-chloropyridine and cooling of the reaction system to -30 °C. Slowly 70mL of 2.0M n-butyllithium dichloromethane solution was added dropwise. After the dropwise addition was completed, stirring was continued for 30 minutes, and then 26 g of 1,4,7-trimethyl-1,4,7-triazacyclononane was slowly added dropwise. After the reaction mixture was kept at -30°C for 2 hours, 26 mL of trimethyl borate was added slowly dropwise and stirring was continued for 1 hour. Subsequently, the reaction system was slowly warmed to room temperature and stirred for 1 hour. 400 g of concentrated hydrochloric acid was added to the reaction mixture and stirred for 1 hour for hydrolysis reaction. Stirring was stopped and allowed to stand for layering. The organic layer was separated and the aqueous layer was extracted three times with 100 g of petroleum ether. All organic layers were combined, dried with 50 g of anhydrous sodium sulfate and filtered. The filtrate was concentrated to dryness under reduced pressure to give 16 g of the target product 5-chloro-2-methoxy-4-pyridineboronic acid.
