Triphenylphosphine → 7-Bromo-5-chloro-2,3-dihydropyrano(4,3,2-de)quinoline

To a stirred solution of 8-bromo-5-hydroxy-4-(2-hydroxyethyl)quinolin-2(1H)-one (0.560 g; 1.971 mmol) in tetrahydrofuran (25 ml) was added triphenylphosphine (0.775 g; 2.96 mmol) followed by the dropwise addition of diisopropyl azodicarboxylate (0.582 ml; 2.96 mmol). The reaction mixture was stirred at room temperature for 2 h, concentrated under reduced pressure and the remaining crude residue was slowly added to phosphorus oxychloride (2.5 ml; 26.7 mmol) at room temperature. The reaction mixture was heated at 100° C. for 1 h and then cooled to room temperature before removing of the volatiles under reduced pressure. The residue was dissolved in dichloromethane, washed with a solution of sodium hydroxide 1N, water and brine, dried over magnesium sulphate and concentrated under reduced pressure. Purification by flash chromatography on silica gel using a gradient of ethyl acetate (5-40%) in heptane furnished 0.220 g (39%) of 7-bromo-5-chloro-2,3-dihydropyrano[4,3,2-de]quinoline as a white solid.

1. concentrationconcentrated under reduced pressure
2. temperatureThe reaction mixture was heated at 100° C. for 1 h
3. temperaturecooled to room temperature
4. custombefore removing of the volatiles under reduced pressure
5. dissolutionThe residue was dissolved in dichloromethane
6. washwashed with a solution of sodium hydroxide 1N, water and brine
7. dry with materialdried over magnesium sulphate
8. concentrationconcentrated under reduced pressure
9. customPurification by flash chromatography on silica gel using a gradient of ethyl acetate (5-40%) in heptane

ORD record

ord-c0966cd9394045a5b4866c0897566676

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08785638B2