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

Temperature

0 °C

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).

1. stirringThe reaction mixture was stirred at 0° C. for 30 min
2. temperatureto warm to ambient temperature
3. stirringstirred overnight
4. customThe aqueous layer was separated
5. extractionextracted with CH2Cl2
6. dry with materialThe combined organic extracts were dried over MgSO4
7. filtrationfiltered
8. concentrationthe filtrate was concentrated
9. customThe crude product was purified by chromatography on a silica gel column

ORD record

ord-729afd91454a4fc68a1d5c285f0d0286

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08101634B2