6-Chloropyridine-2-carbonitrile → (6-Chloropyridin-2-yl)methanamine

Temperature

-5 °C

A 1M solution of lithium aluminium hydride in THF (2.88 ml, 2.88 mmol) was added dropwise to a solution of 6-chloro-2-cyanopyridine (532 mg, 3.84 mmol) in THF (10 ml) at −5° C. under an atmosphere of nitrogen. The mixture was stirred at −5° C. for two hours and the reaction quenched by careful, sequential addition of water (0.1 ml), 15% aqueous sodium hydroxide solution (0.1 ml) and then water (0.3 ml). The mixture was stirred for one hour at 0° C., the insolubles removed by filtration and the filter pad washed thoroughly with methanol. The resulting solution was evaporated and the residue purified by column chromatography on silica gel eluting with DCM/methanol/ammonia (95:5:0 increasing in polarity to 90:10:1) to give the title compound. (215 mg, 40%) as an oil. NMR (DMSO): 2.10 (br s, 2H), 3.75 (s, 2H), 7.30 (d, 1H), 7.55 (d, 1H), 7.80 (t, 1H).

1. customthe reaction quenched by careful,
2. additionsequential addition of water (0.1 ml), 15% aqueous sodium hydroxide solution (0.1 ml)
3. stirringThe mixture was stirred for one hour at 0° C.
4. customthe insolubles removed by filtration
5. washthe filter pad washed thoroughly with methanol
6. customThe resulting solution was evaporated
7. customthe residue purified by column chromatography on silica gel eluting with DCM/methanol/ammonia (95:5:0 increasing in polarity to 90:10:1)

ORD record

ord-7a31a6aa077e4c3c966732a6bf8bab4b

Source dataset

uspto-grants-2009_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07521453B2