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

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.

1. temperatureThe homogeneous solution was heated in an oil bath at 165° C. for 6 hours
2. temperatureThe reaction mixture was cooled to room temperature
3. stirringThe reaction mixture was stirred
4. temperatureheated to 115° C. for 3 hours
5. temperatureThe mixture was cooled to room temperature
6. customIt was partitioned between ethyl acetate and water
7. customThe organic layer was separated
8. extractionthe aqueous layer was extracted with ethyl acetate
9. washThe combined organic extracts were washed with brine
10. dry with materialdried over MgSO4
11. filtrationfiltered
12. concentrationconcentrated
13. customThe crude product was purified by flash column chromatography

ORD-Eintrag

ord-14a08cc41b5f4753b29be261cb5ca4a3

Quelldatensatz

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08394818B2