General procedure for the synthesis of 6-chloro-4-methoxynicotinic acid from methyl 6-chloro-4-methoxynicotinate: lithium hydroxide (1.84 g, 43.9 mmol) was added to a solution of the intermediate from step 2 (2.94 g, 14.6 mmol) in a mixture of methanol (30 mL), tetrahydrofuran (30 mL) and water (3 mL) at 0°C. The reaction mixture was stirred at room temperature for 3 hours. The volatiles were removed under reduced pressure and the residue was diluted with water and washed with dichloromethane. The aqueous layer was acidified to pH ≈ 3 with sodium bisulfate solution and extracted with dichloromethane. The combined organic layers were dried and the volatiles were removed under reduced pressure to give the target product 6-chloro-4-methoxynicotinic acid (2.7 g, 98% yield).
