Cyanogen Bromide → 4-(Hydroxymethyl)piperidine-1-carbonitrile

Participants

Reaction Conditions

Reaction Steps

A solution of 4-piperidinemethanol (10 g, 86.8 mmol) in CH2Cl2 (20 mL) was added dropwise to a slurry of NaHCO3 (14.6 g, 173.6 mmol) in water (10 mL) at 0° C. The mixture was stirred at 0° C. for 30 min, and then charged with cyanogen bromide (3.0M in CH2Cl2, 32 mL, 95.5 mmol) at 0° C. The reaction mixture was stirred at 0° C. for 30 min, then allowed to warm to ambient temperature, and stirred overnight. The aqueous layer was separated and extracted with CH2Cl2. The combined organic extracts were dried over MgSO4, filtered, and the filtrate was concentrated. The crude product was purified by chromatography on a silica gel column using 0 to 100% EtOAc/hexane to give 7.88 g (65%) of 4-(hydroxymethyl)-1-piperidinecarbonitrile as a tan solid. 1H NMR (400 MHz, CDCl3): δ 3.52 (d, 2H, J=6.4 Hz), 3.50-3.40 (m, 2 H), 3.05-2.95 (m, 2H), 1.77 (m, 2H), 1.68-1.54 (m, 1H) 1.44-1.29 (m, 2H); LRMS (ESI), m/z 141 (M+H).

Provenance & Evidence