Hydrochloric Acid → Ethyl 6-chloro-4-hydroxy-3-quinolinecarboxylate

Participants

Reaction Steps

A mixture of 4-chloroaniline (156.7 mmol) and ethyl ethoxymethylenemalonate (156.7 mmol) was stirred at room temperature until homogeneous. The homogeneous solution was heated in an oil bath at 165° C. for 6 hours. The reaction mixture was cooled to room temperature and 1 N HCl (3 mL) was added. The reaction mixture was stirred and heated to 115° C. for 3 hours. The mixture was cooled to room temperature and then treated with 20 mL of water. The resulting suspension treated with 10 N NaOH solutions to reach the pH about 8. It was partitioned between ethyl acetate and water. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over MgSO4, filtered and concentrated. The crude product was purified by flash column chromatography using a 9:1 v/v hexane:ethyl acetate as solvent to afford title compound (28 g, 71% yield) as a yellow solid.

Provenance & Evidence