4-Bromobiphenyl → 1-[2-(1-Biphenyl-4-ylpiperidin-4-yl)ethyl]-2-oxo-1,2,3,4-tetrahydroquinoline-5-carboxaldehyde

Temperatur

100 °C

Palladium acetate (34 mg, 0.15 mmol), tri-tert-butylphosphine tetrafluoroborate (66 mg, 0.23 mmol) and sodium tert-butoxide (218 mg, 2.27 mmol) were added to a toluene solution (10 ml) of 5-(1,3-dioxolan-2-yl)-1-(2-piperidin-4-ylethyl)-3,4-dihydro-1H-quinolin-2-one (500 mg, 1.52 mmol) and 4-bromobiphenyl (424 mg, 1.82 mmol), followed by stirring in an argon atmosphere at 100° C. for 7.5 hours. After cooling to room temperature, water was added to the reaction mixture, and extraction with ethyl acetate was performed. The extract was dried over sodium sulfate and concentrated under reduced pressure, and the residue was purified by basic silica gel column chromatography (n-hexane:ethyl acetate=2:1). The purified product was concentrated under reduced pressure, and the residue was dissolved in acetone (10 ml). p-Toluenesulfonic acid monohydrate (104 mg) and water (2 ml) were added, followed by heating under reflux for 15 minutes. The resulting mixture was cooled to room temperature and concentrated under reduced pressure. The residue was rendered basic by adding an aqueous solution of potassium carbonate, and washed for 10 minutes in an ultrasonic washing machine. The produced insoluble matter was collected by filtration, washed with water and dried to thereby obtain 213 mg (yield: 32.1%) of 1-[2-(1-biphenyl-4-ylpiperidin-4-yl)ethyl]-2-oxo-1,2,3,4-tetrahydroquinoline-5-carboxaldehyde as a colorless solid.

1. temperatureAfter cooling to room temperature
2. dry with materialThe extract was dried over sodium sulfate
3. concentrationconcentrated under reduced pressure
4. customthe residue was purified by basic silica gel column chromatography (n-hexane:ethyl acetate=2:1)
5. concentrationThe purified product was concentrated under reduced pressure
6. dissolutionthe residue was dissolved in acetone (10 ml)
7. additionp-Toluenesulfonic acid monohydrate (104 mg) and water (2 ml) were added
8. temperatureby heating
9. temperatureunder reflux for 15 minutes
10. temperatureThe resulting mixture was cooled to room temperature
11. concentrationconcentrated under reduced pressure
12. additionby adding an aqueous solution of potassium carbonate
13. washwashed for 10 minutes in an ultrasonic washing machine
14. filtrationThe produced insoluble matter was collected by filtration
15. washwashed with water
16. customdried

ORD-Eintrag

ord-85906ae623154310b72d4a48ad1dadbd

Quelldatensatz

uspto-grants-2010_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07777038B2