Chloroacetaldehyde → Ethyl imidazo[1,2-a]pyridine-6-carboxylate

Participants

Reaction Steps

A mixture of 2-amino-5-pyridine carboxylic acid ethyl ester (4.5 g, 27.1 mmol), chloroacetaldehyde (5.7 ml, 40.6 mmol, 45% w/w in water) and toluene (125 ml) was heated to reflux and water was collected in a Dean Stark trap. After 3 hours at reflux the reaction mixture was cooled to room temperature and the resulting precipitate was collected by filtration and washed with ether. The solid was dissolved in water and the solution was neutralized by the addition of concentrated aqueous ammonium hydroxide. The aqueous layer was extracted with chloroform, the organic layer was washed with brine and the solvent was removed in vacuo. The residue was dissolved in ethyl acetate, treated with charcoal and passed through a plug of silica. Removal of the solvent in vacuo afforded 3.1 g (60%) of 6-carboethoxy imidazo[1,2-a]-pyridine as an off-white solid, m.p. 93°-94° C. when recrystallized from tert-butylmethyl ether and dried for 16 hours at 50° C. in high vacuum.

Provenance & Evidence