Synthesis
Step 3: Synthesis of 6-chloro-5-fluoropyridinecarboxylic acid
Methyl 6-chloro-5-fluoropyridinecarboxylate (1.35 g, 7.095 mmol) was dissolved in a solvent mixture of THF and H2O (6:1, 42 mL, v/v), followed by addition of lithium hydroxide monohydrate (596 mg, 14.19 mmol). The reaction mixture was stirred at room temperature for 3 hours. Upon completion of the reaction, the reaction solution was concentrated under reduced pressure, distilled water (20 mL) was added to dissolve the residue, and the solution was acidified by slow dropwise addition of 1N HCl aqueous solution. The acidified solution was extracted with 5% MeOH/MC (30 mL × 2). The organic layers were combined, dried with anhydrous sodium sulfate, filtered, concentrated and dried under vacuum to give 1.04 g of white solid product in 80% yield.
