2-Aminopyridine → 2-Chloromethyl-imidazo(1,2-A)pyridine

Participants

Reaction Steps

7.09 g (54.1 mmol) of 1,3-dichloroacetone were solubilised in 13 ml of DME, to this solution were added with magnetic stirring, 5 g (52.1 mmol) of 2-aminopyridine. The mixture was stirred at r.t. for 16 h. The solid formed was isolated by filtration and washed with 30 ml of diisopropyl ether. This yellow solid was suspended in 125 ml of absolute ethanol and the mixture was stirred with reflux for 2 h. The mixture was concentrated in vacuo and then the obtained residue was taken up in 150 ml of a mixture consisting of water and ice. The pH of the aqueous phase was basified up to pH 8-9 by adding a saturated NaHCO3 aqueous solution. The aqueous phase was extracted with 3×100 ml of dichloromethane. The combined organic phases were washed with 200 ml of a saturated NaCl aqueous solution, dried on Na2SO4 which was then removed by filtration. The obtained filtrate was concentrated in vacuo. The crude residue was purified by flash chromatography on a silica gel cartridge (eluent: heptane/ethyl acetate gradient, from 50% to 40% of heptane, v/v). 4.77 g (yield=55%) of 2-(chloromethyl)imidazo[1,2-a]pyridine were obtained as a white solid. LC-MS: m/z=167 (MH+); UV purity at 254 nm=99%. 1H NMR (300 MHz, DMSO) δ 8.52 (d, J=6.8 Hz, 1H), 7.99 (s, 1H), 7.51 (d, J=9.1 Hz, 1H), 7.32-7.16 (m, 1H), 6.89 (t, J=6.8 Hz, 1H), 4.84 (s, 2H)

Provenance & Evidence