Methanol → Tert-butyl 4-(cyanomethyl)piperazine-1-carboxylate

Participants

Reaction Steps

To a partially dissolved solution of piperazine-1-carboxylic acid tert-butyl ester (2.0 g, 10 mmol) in THF (30 mL) is added 60% NaH (0.44 g, 11 mmol). The resulting solution is stirred for 5 min before the addition of bromoacetonitrile (0.9 mL, 13 mmol). The reaction is stirred for 4 h. MeOH (1 mL) is added and the solution is concentrated and the residue is diluted with EtOAc, washed with 1 N HCl, H2O, NaHCO3 and the solution is dried over MgSO4. The filtrate is concentrated and the crude product is chromatographed using a silica column (50% EtOAc/PE-EtOAc) to yield 4-cyanomethyl-piperazine-1-carboxylic acid tert-butyl ester. 1H NMR (300 MHz, CDCl3) δ4.41 (s, 2H), 4.16 (s, 2H), 3.75 (t, 2H), 3.51 (t, 2H), 1.47 (s, 9H).

Provenance & Evidence