Benzaldehyde → 3-phenylfuro[3,4-c]-pyridine-1-(3H)-one

Temperatur

-30 °C

Under a nitrogen atmosphere, 14.35 g (105.5 mmol) of 2,2,6,6-tetramethylpiperidine was dissolved in tetrahydrofuran (200 ml) as a solvent, and the solution was cooled to −30° C. After that, 60 mL (1.6-mol/L solution, 96.1 mmol) of normal butyllithium was slowly dropped to the solution. After the dropping, the mixture was heated to 0° C., and was stirred for 15 minutes. After that, the mixture was cooled to −70° C. A solution (100 ml) of 5.00 g (48.0 mmol) of isonicotinonitrile in tetrahydrofuran was dropped over 15 minutes to the mixture at −70° C. After the mixture had been stirred at −70° C. for an additional 30 minutes, a solution (50 ml) of 10.2 g (96.1 mmol) of benzaldehyde in tetrahydrofuran was dropped over 5 minutes to the mixture. After having been stirred at −70° C. for an additional 30 minutes, the mixture was slowly heated to 0° C., and water was added to the mixture to stop the reaction. Chloroform was added to the mixture to separate an organic layer, and the layer was washed with water four times. After that, the solvent was removed by distillation, and chloroform (50 ml) and 35 g of silica gel were added to the resultant residue. The mixture was stirred under heat and reflux for 6 hours, and then stirred under heat and reflux for 3 hours with addition of acetic acid. After the mixture had been cooled to room temperature, the solvent was removed by distillation again. The resultant residue was purified by silica gel column chromatography (toluene:ethyl acetate=8:1), whereby 2.06 g of Intermediate Compound 3 were obtained.

1. temperatureAfter the dropping, the mixture was heated to 0° C.
2. temperatureAfter that, the mixture was cooled to −70° C
3. stirringAfter the mixture had been stirred at −70° C. for an additional 30 minutes
4. stirringAfter having been stirred at −70° C. for an additional 30 minutes
5. temperaturethe mixture was slowly heated to 0° C.
6. customthe reaction
7. customto separate an organic layer
8. washthe layer was washed with water four times
9. customAfter that, the solvent was removed by distillation, and chloroform (50 ml) and 35 g of silica gel
10. additionwere added to the resultant residue
11. stirringThe mixture was stirred
12. temperatureunder heat
13. temperaturereflux for 6 hours
14. stirringstirred
15. temperatureunder heat
16. temperaturereflux for 3 hours with addition of acetic acid
17. temperatureAfter the mixture had been cooled to room temperature
18. customthe solvent was removed by distillation again
19. customThe resultant residue was purified by silica gel column chromatography (toluene:ethyl acetate=8:1)

ORD-Eintrag

ord-4b337aba984441aa911b84a26b6a153c

Quelldatensatz

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08072137B2