Chloroform → 5-(Hydroxymethyl)nicotinonitrile

Temperature

165 °C

A stirred mixture of 5-hydroxymethyl-3-bromopyridine (8.50 g, 45.2 mmol) and copper (I) cyanide (10.1 g, 11.3 mmol) in pyridine (50 mL) was heated in a sealed pressure reaction vessel at 165° C. for 20 hours. After cooling to 23° C., the mixture was diluted with concentrated ammonium hydroxide (15 mL) and saturated aqueous ammonium chloride (60 mL), after stirring for 2 hours, the mixture was treated with chloroform (50 mL) and allowed to set for 72 hours. The aqueous layer was then extracted with chloroform. The combined organic extracts were dried (MgSO4), filtered, and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, 2 inch column, 4:1 EtOAc:hexane as eluant) followed by crystallization from diethyl ether to afford 5-hydroxymethyl-3-pyridinecarbonitrile (5.42 g, 40.4 mmol, 89% yield): Rf 0.49 (EtOAc); 1H NMR (CDCl3, 200 MHz)δ8.80 (m, 2H), 8.03 (s, 1H), 4.83 (s, 2H).

1. temperatureAfter cooling to 23° C.
2. waitto set for 72 hours
3. extractionThe aqueous layer was then extracted with chloroform
4. dry with materialThe combined organic extracts were dried (MgSO4)
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe residue was purified by flash chromatography (silica gel, 2 inch column, 4:1 EtOAc:hexane as eluant)
8. customfollowed by crystallization from diethyl ether

ORD record

ord-eb2d65ebfb204e508210ae122fbd8280

Source dataset

uspto-grants-1991_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05002949