4-Hydroxy-6-methoxyquinoline

25063-43-8

13788-72-2

1. 4-Methoxyaniline (1.27 g) and 5-methoxymethylene-2,2-dimethyl-[1,3]dioxolane-4,6-dione (1.82 g) were dissolved in 2-propanol (40 mL), and the reaction was stirred for 2 hours at 50°C. The reaction was completed by distillation under reduced pressure. After completion of the reaction, the solvent was removed by distillation under reduced pressure and the residue was washed with ether to afford 5-[(4-methoxyphenylamino)methylene]-2,2-dimethyl-[1,3]dioxolane-4,6-dione (1.98 g, 73% yield). 2. 5-[(4-methoxyphenylamino)methylene]-2,2-dimethyl-[1,3]dioxolane-4,6-dione (1.28 g) and biphenyl (5.2 g) were suspended in diphenyl ether (20 mL) and the reaction was stirred at 220 °C for 1 hour. The reaction mixture was purified by column chromatography in methanol-chloroform system to afford 6-methoxy-1H-quinolin-4-one (398 mg, 49% yield). 3. 6-Methoxy-1H-quinolin-4-one (398 mg) was suspended in diisopropylethylamine (3 mL), phosphorus trichloride (1 mL) was added, and the reaction was stirred at 100 °C for 1 hour. After completion of the reaction, water was added under cooling in an ice bath and the aqueous layer was neutralized with aqueous sodium bicarbonate. The organic layer was extracted with ethyl acetate, the ethyl acetate layer was washed with water and dried with anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure and the residue was purified by column chromatography in acetone-chloroform system to give 4-chloro-6-methoxyquinoline (375 mg, 42% yield).