Step I. Preparation of methyl 2,6-dichloroisonicotinate
A mixed solution of 187 g (0.974 mol) of 2,6-dichloroisonicotinic acid, 1650 ml of methanol and 5 ml of concentrated sulfuric acid was heated and refluxed for 24 hours. After completion of the reaction, most of the solvent was evaporated under reduced pressure to give the crude product. The crude product was dissolved in 750 ml of dichloromethane and washed sequentially with water and 1N sodium hydroxide solution. The organic layer was separated and dried with anhydrous sodium sulfate, followed by evaporation of the solvent under reduced pressure to give 174 g (86.7% yield) of methyl 2,6-dichloroisonicotinate with a melting point of 205 °C.
