25462-85-5

64-17-5

3998-88-7

Step 1: Synthesis of ethyl 2-chloro-6-methylisonicotinate (97). Concentrated sulfuric acid (2 mL) was added dropwise to a stirred solution of 2-chloro-6-methylpyridine-4-carboxylic acid (7.0 g, 40.79 mmol) in ethanol (70 mL) at 0 °C. Subsequently, the reaction mixture was heated to 80 °C and kept for 12 hours. Upon completion of the reaction, the mixture was cooled to room temperature and concentrated under vacuum to remove the solvent. The concentrated residue was diluted with ethyl acetate and washed sequentially with water, sodium bicarbonate solution and saturated aqueous sodium chloride solution. The organic layer was separated, dried over anhydrous sodium sulfate, filtered and concentrated to give ethyl 2-chloro-6-methylisonicotinate (97) (7 g, 86% yield) as a white solid.