Dimethylformamide → 5-Formyl-3-(1-Methylpiperidin-4-yl)-1H-Indole

HRID 277983

Reaktionsgleichung

Reaktionsgleichung von HRID 277983
[H-].[K+].Br[C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[C:7]2[CH:13]1[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]1.C([Li])(C)(C)C.CN(C)[CH:27]=[O:28]>O1CCCC1>[CH:27]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[C:7]2[CH:13]1[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]1)=[O:28]

Komponenten

6

Edukt 4

HCID 6228DimethylformamideHCID 82127Potassium hydrideHCID 157453445-bromo-3-(1-methylpiperidin-4-yl)-1H-indoleHCID 178418306HCID 178418306, Verbindung

Produkt 1

HCID 226267865-Formyl-3-(1-Methylpiperidin-4-yl)-1H-IndoleAusbeute 45,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel3×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a slurry of potassium hydride (20% suspension in mineral oil, 4.30 g, 21.50 mmol) in 80 mL of anhydrous tetrahydrofuran at 0° C. was slowly added dropwise 5-bromo-3-(1-methylpiperidin-4-yl)-1H-indole (6.0 g, 20.5 mmol) in 80 mL of anhydrous tetrahydrofuran. After stirring at 0° C. for 30 minutes, the mixture was cooled to −78° C., and tert-butyl lithium (1.7 M solution in pentane, 45.0 mmol, 26.5 mL) was added dropwise. After 15 minutes, a solution of anhydrous N,N-dimethylformamide (30.7 mmol, 2.4 mL) in 10 mL of anhydrous tetrahydrofuran was added dropwise. The stirred mixture was allowed to warm to room temperature, and was quenched with a 5N aqueous sodium hydroxide solution. The aqueous phase was extracted with diethyl ether, and the ether extracts were separated, washed with brine, dried over sodium sulfate, filtered, concentrated in vacuo and purified by silica gel (flash) chromatography (dichloromethane:methanol 9.5:0.5) to give 2.26 g (45%) of the title product as an oily solid. MS(FD) m/e=242 (M+). EA calculated for C15SH18N2O. ½ H2O: C, 71.69; H, 7.21; N, 11.14. Found: C, 71.38; H, 6.87; N, 11.06.

Aufarbeitung

  1. temperaturethe mixture was cooled to −78° C.
  2. waitAfter 15 minutes
  3. temperatureto warm to room temperature
  4. customwas quenched with a 5N aqueous sodium hydroxide solution
  5. extractionThe aqueous phase was extracted with diethyl ether
  6. customthe ether extracts were separated
  7. washwashed with brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. custompurified by silica gel (flash) chromatography (dichloromethane:methanol 9.5:0.5)

Quellen und Nachweise

ORD-Eintrag
ord-1940e088f51d405abc0b157d8296f5bb
Quelldatensatz
uspto-grants-2002_03
Patentnummer
US06358972B1

Verknüpfte Notizen

Wird geladen…