DIAD (3.92 mL, 19.90 mmol) was added dropwise to a stirred solution of 4-nitro-1H-pyrazole (1.5 g, 13.27 mmol), tert-butyl 4-hydroxypiperidine-1-carboxylate (2.67 g, 13.27 mmol) and triphenylphosphine (5.22 g, 19.90 mmol) in THF (30 mL) cooled to 0° C. under a nitrogen atmosphere. The resulting solution was stirred at 0° C. for 10 minutes then allowed to warm to room temperature and stirred overnight. The mixture was diluted with isohexane (80 mL) and EtOAc (20 mL) and then stirred vigorously. The mixture was filtered and the solid washed with isohexane (20 mL). The combined filtrates were evaporated and the residue was purified by chromatography on silica, eluting with a gradient of 20-50% EtOAc in isohexane. Fractions containing product were combined and evaporated to afford tert-butyl 4-(4-nitropyrazol-1-yl)piperidine-1-carboxylate (3.63 g, 92% yield); 1H NMR spectrum: (300 MHz, DMSO) 1.42 (9H, s), 1.79-1.84 (2H, m), 2.01-2.05 (2H, m), 2.87-2.98 (2H, m), 4.40-4.47 (1H, m), 8.28 (1H, s), 8.95 (1H, s). b) A mixture of tert-butyl 4-(4-nitropyrazol-1-yl)piperidine-1-carboxylate (3.63 g, 12.25 mmol) and 10% palladium on carbon (0.326 g, 0.31 mmol) in EtOH (200 mL) were stirred under an atmosphere of hydrogen for 18 hours. The mixture was filtered through Celite and the filtrate loaded onto an SCX column. The mixture was eluted first with MeOH and then with a 7M solution of NH3 in MeOH. Fractions containing product were combined and evaporated to afford tert-butyl 4-(4-aminopyrazol-1-yl)piperidine-1-carboxylate (2.100 g, 64% yield); 1H NMR spectrum: (300 MHz, DMSO) δ 1.41 (9H, s), 1.65-1.74 (2H, m), 1.89-1.92 (2H, m), 2.81-2.93 (2H, m), 3.75 (2H, s), 3.99 (2H, d), 4.09-4.16 (1H, m), 6.91 (1H, s), 7.06 (1H, s); Mass spectrum: m/z (ESI+) (M+H)+=211.0.
