Preparation of 4-amino-2-chloronicotinic acid: 4-amino-2-chloronicotinic acid methyl ester (21.0 g, 112.9 mmol) and LiOH (10.3 g, 247.5 mmol) were added to a solvent mixture of dioxane:MeOH:water (3:2:1). The reaction mixture was heated to 85 °C and kept for 2 hours. The solvent was removed by evaporation under reduced pressure and the residue was dissolved in a minimum volume of water and acidified to pH 4 with saturated citric acid solution. the aqueous solution was concentrated until a precipitate just started to appear. The mixture was allowed to stand overnight at 10°C to allow complete precipitation. The resulting white solid was collected by filtration and recrystallized from the mixture of isopropanol-hexane solvent to give 4-amino-2-chloronicotinic acid (13 g, 66% yield).1H NMR (400 MHz, DMSO-d6): δ 7.59 (d, 1H), 6.47 (d, 1H), 6.37 (brs, 2H).
