Butyl vinyl ether → 1-(6-Fluoroquinolin-8-yl)ethan-1-one

Temperature

90 °C

To a solution of 6-fluoro-8-bromo-quinoline (1.53 g, 6.8 mmol) in acetonitrile (35 mL) was added palladium(II) acetate (0.31 g, 1.36 mmol, 0.2 eq.), butyl vinyl ether (2.04 g, 20 mmol, 3.0 eq.), and 1,3-bis(diphenylphosphino)propane (0.70 g, 1.7 mmol, 0.25 eq) was added triethylamine (1.1 g, 11 mmol, 1.6 eq). The resulting mixture was heated to 90° C. for 17 hr and then evaporated under reduced pressure. The residue was dissolved in aqueous hydrochloric acid (2M, 15 mL) and stirred, at room temperature, for 1.5 hr. This mixture was then diluted with water (35 mL) and the pH adjusted with solid sodium hydrogen carbonate until neutral. The mixture was then extracted with ethyl acetate (100 mL); the organic phase was dried over magnesium sulphate. The resulting mixture was filtered and concentrated under reduced pressure to give a brown oil. This crude product was purified by chromatography on silica gel eluting with 10% ethyl acetate in pentane (by volume) to produce the title compound as a pale yellow solid (0.91 g, 71%).

1. customevaporated under reduced pressure
2. dissolutionThe residue was dissolved in aqueous hydrochloric acid (2M, 15 mL)
3. additionThis mixture was then diluted with water (35 mL)
4. extractionThe mixture was then extracted with ethyl acetate (100 mL)
5. dry with materialthe organic phase was dried over magnesium sulphate
6. filtrationThe resulting mixture was filtered
7. concentrationconcentrated under reduced pressure
8. customto give a brown oil
9. customThis crude product was purified by chromatography on silica gel eluting with 10% ethyl acetate in pentane (by volume)

ORD record

ord-f42c6b7281f640fa86089c8eeda44af2

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08916593B2