Sulfuric Acid → 6-Chloro-8-methoxyquinoline

Temperature

140 °C

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%):

1. filtrationfiltered through celite
2. customthe layers separated
3. extractionThe aqueous layer was extracted with DCM (2×500 mL)
4. washthe combined organic layers were washed with brine (500 mL)
5. dry with materialdried over anhydrous sodium sulfate
6. concentrationconcentrated in vacuo
7. customThe resulting crude product was purified with silica gel chromatography
8. washeluting with 20% EtOAc in petroleum ether

ORD record

ord-6b80d4b4f3ca4b5f941a386492eabbba

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08592629B2