Sodium Hydroxide → Tert-butyl 4-(aminomethyl)-4-(cyclopropylmethyl)piperidine-1-carboxylate

Participants

Reaction Steps

A solution of the tert-butyl 4-cyano-4-cyclopropylmethylpiperidine-1-carboxylate (I-2) (1.00 g, 3.78 mmol) in ethanol (5 mL) was added to 1M sodium hydroxide in 95% ethanol-water (75 mL) and the solution degassed with nitrogen. Raney Nickel (50% slurry in water) (2.6 g) was added and the black suspension shaken under hydrogen pressure (40 psi) at room temperature for 12 h. The catalyst was filtered off and washed with 95% ethanol-water. The filtrate was evaporated in vacuo then partitioned between water and DCM. The organic phase was separated and the aqueous phase re-extracted with DCM twice. The combined organic phase was dried (MgSO4) and the solvent removed in vacuo to leave tert-butyl 4-aminomethyl-4-cyclopropylmethylpiperidine-1-carboxylate (I-3) that was used in the next step without further purification. 1H NMR (500 MHz, CDCl3): δ 3.44 (m, 2H), 3.32 (m, 2H), 2.71 (s, 2H), 1.41 (s, 9H), 1.46-1.38 (m, 4H), 1.28 (d, J=6.7, 2H), 1.46 (s, 9H), 0.60 (m, 1H), 0.46 (m, 2H), 0.05 (m, 2H).

Provenance & Evidence