Formamide → 5-[(4-Chlorophenyl)methoxy]pyridine-2-carboxamide

Participants

Reaction Steps

To 3-(4-chlorobenzyloxy)pyridine (2.19 g, 10 mmol) in formamide (10 ml) at 10° is slowly added conc. sulfuric acid. The reaction is then cooled to 5°, and FeSO4.7H2O (4.16 g, 15 mmol), finely powdered, and hydrogen peroxide (1.7 ml of 30% solution, 0.51 g of H2O2, 15 mmol) are added simultaneously over 10 minutes, with rapid stirring and cooling to 12°-18°. After addition is complete, the reaction is allowed to sit at RT overnight. Ethyl acetate and water are added to the reaction slurry. The layers are separated, and the aqueous phase is extracted with ethyl acetate (3X). The combined organic layers are washed with water and with brine and are dried over calcium sulfate. The residue is taken up in ether, leaving an oily residue. The oily residue is then taken up in chloroform, washed with sat. sodium carbonate, with water and with brine and purified by preparative thin layer chromatography (developing with 50% ethyl acetate/hexane and 0.05% ammonium hydroxide). The second band is collected, yielding 5-(4-chlorobenzyloxy)pyridine-2-carboxamide.

Provenance & Evidence