Methanol → 2-(Hydroxymethyl)pyridine-4-carbonitrile

A solution of 4-cyanopyridine (5.20 g, 50.0 mmol) in 90 ml of methanol is treated with a mixture of H2SO4 (6.42 g, 65.5 mmol, 1.31 equiv.) and water (45 ml) at once followed by the addition of (NH4)2S2O8 (22.8 g, 100 mmol, 2.0 equiv.). The contents were heated to reflux at which point vigorous refluxing ensued for several minutes. After refluxing for 24 h, the reaction mixture is partially concentrated to remove most of the methanol, treated with ice-water mixture and basified with ammonium hydroxide (20 ml, 29% aq). The residue is extracted four times with chloroform, the combined extracts are dried with anhyrous Na2SO4 and concentrated at reduced pressure. Chromatography is accomplished using 300 g of silica gel packed and eluted with acetone-methylene chloride (1:6) to provide 2.65 g (39.5%) of 4-Cyano-2-hydroxymethylpyridine.

1. temperatureThe contents were heated
2. temperatureto reflux at which point
3. temperaturevigorous refluxing
4. waitensued for several minutes
5. temperatureAfter refluxing for 24 h
6. concentrationthe reaction mixture is partially concentrated
7. customto remove most of the methanol
8. additiontreated with ice-water mixture
9. extractionThe residue is extracted four times with chloroform
10. dry with materialthe combined extracts are dried with anhyrous Na2SO4
11. concentrationconcentrated at reduced pressure
12. washeluted with acetone-methylene chloride (1:6)

ORD record

ord-96da7b6fa48243259cbc50437ef4fcbf

Source dataset

uspto-grants-2000_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06043248