Sulfuric Acid → 6-Chloro-8-methoxyquinoline

Participants

Reaction Conditions

Reaction Steps

Concentrated sulphuric acid (40 mL) was added to a mixture of 4-chloro-2-anisidine hydrochloride (20 g, 127 mmol), m-nitrobenzene sulfonic acid sodium salt (42.4 g, 190 mmol), boric acid (10 g, 161.8 mmol), ferrous sulfate (6.0 g, 21.5 mmol) and glycerol (400 mL) at room temperature. The mixture was heated at 140° C. for 30 minutes. The reaction mixture was diluted with water (500 mL) and the pH adjusted to 10 with 10% aqueous sodium hydroxide solution. DCM (1 L) was added, stirred for 30 minutes, filtered through celite and the layers separated. The aqueous layer was extracted with DCM (2×500 mL) and the combined organic layers were washed with brine (500 mL), dried over anhydrous sodium sulfate and concentrated in vacuo. The resulting crude product was purified with silica gel chromatography eluting with 20% EtOAc in petroleum ether to yield the title compound as a liquid (14.2 g, 58%):

Provenance & Evidence