2-Chloro-5-fluoropyridine

5350-93-6

31301-51-6

The general procedure for the synthesis of 2-chloro-5-fluoropyridine from 2-chloro-5-aminopyridine is as follows: in a 25-mL three-necked flask equipped with a reflux condenser, thermocouple, and stirring system, 1 g (7.78 mmol) of 2-chloro-5-aminopyridine was dissolved in 14.3 g of o-dichlorobenzene, and added dropwise over a 5-min period of 5 min at room temperature to 1.64 g (11.5 mmol, 1.47 molar equivalents) of the boron trifluoride ethyl ether complex. Upon completion of the dropwise addition, the reaction solution was beige in color and accompanied by the formation of a precipitate. Subsequently, the reaction system was heated to 105 °C and maintained for 20 minutes before 1.05 g (9.2 mmol, 1.18 mole equivalents, 90% purity) of tert-butyl nitrite was added to 5.0 g of o-dichlorobenzene at a controlled titration rate of 25 ml/hr. The reaction was kept at 105 °C and continued for 25 min, after which the heating was stopped. The yield of 2-chloro-5-fluoropyridine was 36% as determined by 19F NMR.