The general procedure for the synthesis of N-Boc-cyano-piperidin-4-one from ethyl 3-((tert-butoxycarbonyl)(2-cyanoethyl)amino)propionate was as follows: ethyl 3-((tert-butoxycarbonyl)(2-cyanoethyl)amino)propionate (17.3 g, 64.0 mmol) was dissolved in 200 mL of toluene and 60% sodium hydride (3.84 g, 96.0 mmol). The reaction mixture was heated to reflux and maintained for 3 hours. Upon completion of the reaction, it was cooled to room temperature, diluted with 200 mL of water, and the pH was subsequently adjusted to 3 with 1 N hydrochloric acid solution.The aqueous phase was extracted with ethyl acetate (200 mL x 3). The organic phases were combined, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with ethyl acetate/petroleum ether as eluent to afford 7.8 g (51.6% yield) of tert-butyl 3-cyano-4-oxopiperidine-1-carboxylate as a white solid.1H NMR (400 MHz, DMSO-d6) δ 10.87 (s, 1H), 3.89 (s, 2H), 3.46 (t, J=5.8Hz. 2H), 2.28 (t, J=5.8Hz, 2H).
