Synthesis
3-Fluoropyridine (25 g, 257 mmol) was slowly added dropwise to a solution of tetrahydrofuran (600 mL) containing butyl lithium (270 mmol) and diisopropylamine (27.4 g, 271 mmol) at -78 °C. The reaction mixture was stirred continuously at this temperature for 1 hour. Subsequently, crushed dry ice was added to the reaction system and gradually warmed to room temperature over 1 hour. Upon completion of the reaction, the pH of the reaction solution was adjusted to 5 with an aqueous solution of hydrogen chloride and acidified. The resulting precipitate was collected by filtration and dried. The final 3-fluoroisonicotinic acid (25.2 g, 179 mmol, 70% yield) was obtained as colorless crystals.
