Dimethylformamide → (E)-3-[3-(4-Fluorophenyl)-1-isopropyl-1H-indol-2-yl]-acrylic Acid

HRID 352101Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 352101
Br[C:2]1[N:3]([CH:18]([CH3:20])[CH3:19])[C:4]2[C:9]([C:10]=1[C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1)=[CH:8][CH:7]=[CH:6][CH:5]=2.CN(C=O)C.C(=O)([O-])[O-].[Cs+].[Cs+].[C:32]([OH:36])(=[O:35])[CH:33]=[CH2:34]>O>[F:17][C:14]1[CH:15]=[CH:16][C:11]([C:10]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[N:3]([CH:18]([CH3:20])[CH3:19])[C:2]=2/[CH:34]=[CH:33]/[C:32]([OH:36])=[O:35])=[CH:12][CH:13]=1

Komponenten

6

Edukt 4

HCID 6228DimethylformamideHCID 6581Acrylic AcidHCID 10796Cesium carbonateHCID 227150602-bromo-3-(4-fluorophenyl)-1-isopropyl-1H-indole

Produkt 1

HCID 22715053(E)-3-[3-(4-Fluorophenyl)-1-isopropyl-1H-indol-2-yl]-acrylic Acid

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Versuchsvorschrift

2 g (6.02 mmol) of 2-bromo-3-(4-fluorophenyl)-1-isopropyl-1H-indole, 10 ml of DMF and 0.5 ml of water are introduced into a 50 ml three-necked, round-bottomed flask, which has been purged with nitrogen and is equipped with a magnetic stirrer, thermometer, reflux condenser, gas inlet tube and nitrogen delivery line, and degassing is carried out for 30 min. by introducing nitrogen. 24 mg (1.0 mol %) of the catalyst K4 from WO-A-99/47474 and 2.15 g (6.6 mmol) of caesium carbonate are then added and degassing is carried out for a further 1 hour. 1.0 g (13.8 mmol) of acrylic acid are subsequently added and the suspension is heated at reflux for 2 hours. The DMF is then distilled off, the residue is cooled, 10 ml of 1N hydrochloric acid are added and the aqueous phase is extracted three times with 50 ml of ethyl acetate. The combined organic phases are washed three times with 30 ml of saturated sodium carbonate solution, slightly acidified again using 1N hydrochloric acid, and washed three times with 50 ml of saturated sodium chloride solution in order to render neutral. Drying over magnesium sulfate, filtration and concentration by evaporation are then carried out. The residue (1.83 g) is dissolved in THF, 5 g of silica gel are added and the solution is concentrated by evaporation using a rotary evaporator. The charged silica gel is transferred into a glass frit, and non-polar secondary products are eluted using hexane/ethyl acetate=10:1 and then the product is eluted using ethyl acetate. Concentration by evaporation yields a yellow solid which, according to NMR, is the desired product in pure form.

Aufarbeitung

  1. customround-bottomed flask, which has been purged with nitrogen
  2. customis equipped with a magnetic stirrer
  3. temperaturethermometer, reflux condenser, gas inlet tube
  4. customnitrogen delivery line, and degassing
  5. additionby introducing nitrogen
  6. customdegassing
  7. waitis carried out for a further 1 hour
  8. temperaturethe suspension is heated
  9. temperatureat reflux for 2 hours
  10. distillationThe DMF is then distilled off
  11. temperaturethe residue is cooled
  12. addition10 ml of 1N hydrochloric acid are added
  13. extractionthe aqueous phase is extracted three times with 50 ml of ethyl acetate
  14. washThe combined organic phases are washed three times with 30 ml of saturated sodium carbonate solution
  15. washwashed three times with 50 ml of saturated sodium chloride solution in order
  16. dry with materialDrying over magnesium sulfate, filtration and concentration by evaporation
  17. dissolutionThe residue (1.83 g) is dissolved in THF
  18. addition5 g of silica gel are added
  19. concentrationthe solution is concentrated by evaporation
  20. customa rotary evaporator
  21. washare eluted
  22. washthe product is eluted
  23. concentrationConcentration
  24. customby evaporation
  25. customyields a yellow solid which

Quellen und Nachweise

ORD-Eintrag
ord-32209762a4034378b630a880249f97bf
Quelldatensatz
uspto-grants-2004_06
Patentnummer
US06743926B2

Notizen zur Reaktion

Wird geladen…