General procedure for the synthesis of tert-butyl 3-cyanopiperidine-1-carboxylate (3) from N-BOC-3-piperidinecarboxamide: To a solution of tert-butyl-3-carbamoylpiperidine-1-carboxylate (2) (1.0 g, 4 mmol) in anhydrous methylene chloride (20 mL) was added triethylamine (3.1 g, 31.0 mmol), followed by a slow, dropwise addition of trifluoroacetic acid anhydride (4.1 g , 20.0 mmol). The reaction mixture was gradually warmed to room temperature and stirred continuously for 16 hours. Upon completion of the reaction, the mixture was partitioned between dichloromethane (50 mL) and water (50 mL). The organic phase was washed with saturated sodium bicarbonate solution (100 mL) and subsequently dried over anhydrous sodium sulfate. The organic phase was concentrated under reduced pressure to give a viscous liquid product 3 (800 mg, 87% yield).1H NMR (400 MHz, CDCl3) δ 1.49 (s, 9H), 1.77 (m, 2H), 1.97 (brs, 1H), 2.66 (m, 1H), 3.35-3.84 (brs, 4H).
