To a 5000 mL three-necked flask, add 3500 mL of the above already prepared methanol solution of hydrogen chloride, 350 g of 5-bromo-2-chloroisonicotinic acid, raise the temperature to 40C and stir the reaction, track the reaction by liquid chromatography, and stop the reaction when the product, methyl 5-bromo-2-chloroisonicotinate, is greater than 85% by liquid chromatography, and the content of the methyl 5-bromo-2-methoxyisonicotinate by-product (3) is less than 1%. Reaction. Neutralize the system with solid sodium bicarbonate to neutral under stirring, filter, drain, rinse the filter cake with methanol, combine the filtrates and concentrate to obtain a brownish-red liquid 320 g, high vacuum distillation, collect 40-60 Pa, 70-75 fractions, obtain a colorless liquid 5-bromo-2-chloroisonicotinic acid methyl ester (296 g), content of 98.9%.
