General procedure for the synthesis of (R)-1-BOC-2-cyanopiperidine from R-N-Boc-prolinamide: b) Synthesis of 1,1-dimethylethyl (2R)-2-(aminocarbonyl)-1-pyrrolidine carboxylate. To a solution of 1,1-dimethylethyl (2R)-2-(aminocarbonyl)-1-piperidine carboxylate (269 mg, 1.17 mmol) in tetrahydrofuran (THF, 10 mL) was added sequentially triethylamine (0.33 mL, 2.34 mmol) and trifluoroacetic anhydride (0.17 mL, 1.17 mmol) at 0 °C. The reaction mixture was stirred at 0 °C for 1 h and then concentrated under vacuum. The concentrated residue was dissolved in ethyl acetate (EtOAc) and washed sequentially with saturated sodium bicarbonate solution, 0.5 N hydrochloric acid and brine. The organic phase was dried with anhydrous sodium sulfate (Na2SO4), filtered and concentrated to afford 1,1-dimethylethyl (2R)-2-cyano-1-piperidine carboxylate (255 mg, 99% yield) as a crystalline solid. The 1H NMR (CDCl3) data of the product were as follows: δ 5.23 (br, 1H), 4.05 (br, 1H), 2.93 (br, 1H), 1.93-1.39 (m, 6H), 1.46 (s, 9H).
