General procedure for the synthesis of 2-chloro-3-fluoropyridine from 3-fluoropyridine: n-butyllithium (2.5 M hexane solution, 230 ml, 0.57 mol) was added to a solution of 1,4-diazabicyclo[2.2.2]octane (63.8 g, 0.57 mol) in ether (2.5 L) that had been pre-removed from water by azeotropic boiling, at -20 to -30 °C. After stirring for 1 hour, the temperature was adjusted to -65°C. A solution of 3-fluoropyridine (50.0 g, 0.52 mol) in ether (250 ml) was added dropwise over 10 minutes and the mixture was stirred for another 1 hour. Then an ether (350 ml) solution of hexachloroethane (136.5 g, 0.58 mol) was added dropwise over 15 minutes, keeping the temperature below -60°C, and the mixture was stirred for 2 hours. The reaction was quenched by addition of saturated aqueous NH4Cl solution (250 ml), warmed to ambient temperature and separated. The aqueous phase was extracted with ether (2 x 250 ml) and the combined organic phases were washed with saturated aqueous NH4Cl solution (250 ml), dried over anhydrous MgSO4 and concentrated in vacuum. The residue was diluted with isohexane (150 ml), washed with 2N hydrochloric acid (3 x 100 ml) and then with 37% hydrochloric acid (3 x 50 ml). The acid wash was then extracted with isohexane (3 x 100 ml), alkalized to pH 14 by careful addition of 4N aqueous NaOH (500 ml) and re-extracted with CH2Cl2 (3 x 150 ml). The organic fraction was dried over anhydrous MgSO4 and concentrated in vacuum. The residue was purified by distillation (boiling point 74-82 °C, 1 atm) to give 2-chloro-3-fluoropyridine as a straw-colored oil (42.6 g, 63%).
