To a solution of 9.0 g 1-BOC-4-piperidinecarbohydrazide (37 mmol, 1 eq.) in 40 mL of THF was added 8.1 mL of N,N-dimethylformamide dimethyl acetal (55.4 mmol, 1.5 eq.). The reaction mixture was stirred under nitrogen protection at 50 °C for 4 hours. After completion of the reaction, the solvent was removed under reduced pressure and the residue was dissolved in 40 mL of toluene and 400 mg of p-toluenesulfonic acid was added. The mixture was heated at 100 °C and protected by nitrogen for 18 hours. At the end of the reaction, the volatiles were removed under reduced pressure and the residue was partitioned between dichloromethane and aqueous sodium bicarbonate. The organic phase was dried with magnesium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography with the eluent dichloromethane/methanol (98:2 v/v to 95:5 v/v) to afford 8.07 g of 1-Boc-4-(5-methyl-1,3,4-oxadiazol-2-yl)piperidine as a white solid in 81% yield.1H NMR (400 MHz, CD3OD): δ 1.42 (s, 9H), 1.70 (m , 2H), 2.05 (m, 2H), 2.50 (s, 3H), 3.00 (m, 2H), 3.15 (m, 1H), 4.05 (m, 2H); LCMS: m/z APCl+, 268 [MH]+; Elemental analysis results: C, 58.26%; H, 7.96%; N, 15.78%; theoretical value (C13H21N3O3 ): C, 58.41%; H, 7.92%; N, 15.72%.
