5-(Trifluoromethyl)nicotinonitrile

Synthesis

557-21-1

436799-33-6

951624-83-2

Example 1.1.27: Synthesis of (5-(trifluoromethyl)pyridin-3-yl)methanamine: 3-bromo-5-(trifluoromethyl)pyridine (1.0 g, 4.42 mmol, 1 eq.) was dissolved in 20 mL of anhydrous DMF. The solution was degassed by argon bubbling. Zinc cyanide (Zn(CN)2, 0.312 g, 2.65 mmol, 0.6 eq.) and tetrakis(triphenylphosphine)palladium (Pd(PPh3)4) were subsequently added and the resulting reaction mixture was heated to 80 °C and stirred overnight. Upon completion of the reaction, the mixture was cooled to room temperature and diluted with ether (Et2O). The organic and aqueous layers were separated by adding 28% ammonia (NH4OH) with continuous stirring. The organic layer was sequentially washed three times with water, once with brine and dried with anhydrous sodium sulfate (Na2SO4). After filtration to remove inorganic salts, the filtrate was concentrated under reduced pressure. Finally, it was purified by silica gel fast column chromatography to obtain 5-(trifluoromethyl)nicotinonitrile (0.310 g, 1.95 mmol, 44% yield).

References