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

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Reaction Steps

A mixture of 2-aminopyridine (Aldrich; 0.487 g), 1,3-dichloroacetone (Aldrich; 0.73 g), and dimethoxyethane (6 mL) is stirred at room temperature for 2.5 h and then at 60° C. for 30 min. Dimethoxyethane is then removed under reduced pressure and ethanol (10 mL) is added. The mixture is stirred at 80° C. for 20 min and then cooled and concentrated under reduced pressure. The residue is partitioned between dichloromethane and aq. sodium bicarbonate and the organic layers are filtered through sodium sulfate and concentrated. Dichloromethane and ethyl acetate are added to the residue and the solids are removed by filtration. The filtrate is concentrated and the residue is chromatographed on silica gel using ethyl acetate/hexane (50/50) to give 0.495 g of 2-(chloromethyl)imidazo[1,2-a]pyridine; mp >255° C.; 1H NMR (CDCl3) δ 4.78, 6.80, 7.19, 7.58, 7.62, 8.08.

Provenance & Evidence