Method 2: Concentrated nitric acid (14 mL) was slowly added to concentrated sulfuric acid (43 mL) that had been pre-cooled to 0°C, ensuring that the temperature of the reaction system was maintained below 10°C. The reaction system was then heated to 70°C. The reaction system was then heated to 70°C. After addition, the mixed acid solution was warmed to 70 °C, followed by the addition of commercially available 2,6-dichloro-4-methylnicotinonitrile (20.0 g, 107 mmol). The heating was continued until the internal temperature of the reaction system reached 105°C. The heating was stopped. After 2 hours of reaction, TLC monitoring showed complete reaction. The reaction mixture was cooled to room temperature and quenched by slowly pouring into ice (100 g) under vigorous stirring. The precipitated solid was collected by filtration and washed with cold water (10 mL). The resulting solid was dissolved in ethyl acetate (100 mL) and the solution was dried over anhydrous sodium sulfate and concentrated to give 2,6-dichloro-4-methylnicotinic acid (21.0 g, 96% yield) as a white solid: Rf = 0.20 (unfolding reagent ratio 1:1 ethyl acetate/hexane solvent mixture).
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