The general procedure for the synthesis of 5-fluoropyridine-2-carboxylic acid from ethyl 5-fluoropyridine-2-carboxylate is as follows: 5-fluoropyridine-2-carboxylic acid (200 mg, 1.13 mmol) was reacted with ethanol (6 mL) and a dioxane solution of 4M HCl (0.5 mL) for 20 hours at 90°C. After completion of the reaction, the mixture was concentrated and mixed with saturated sodium carbonate solution and dichloromethane. The organic layer was separated, washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give ethyl 5-fluoropyridine-2-carboxylate (94 mg, 49.3% yield). Subsequently, ethyl 5-fluoropyridine-2-carboxylate (94 mg, 0.556 mmol) was dissolved in dichloromethane (4.0 mL) at room temperature, and a toluene solution of 1M DIBAL (1.23 mL, 1.23 mmol) was slowly added. The reaction mixture was stirred for 30 min, then the reaction was quenched with 2 M sodium carbonate solution and extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product 5-fluoropyridine-2-carboxaldehyde (39 mg, 54.7% yield), which could be used directly in the subsequent reaction without further purification.GC-MS analysis showed a molecular ion peak (M+) of 125.
