Bromoacetone → 2-Methylindolizine-6-carbonitrile

HRID 402887

Reaktionsgleichung

Reaktionsgleichung von HRID 402887
Br[CH2:2][C:3](=O)[CH3:4].[C:6]([C:8]1[CH:9]=[CH:10][C:11]([CH3:14])=[N:12][CH:13]=1)#[N:7]>S1(CCCC1)(=O)=O.CCOC(C)=O>[CH3:4][C:3]1[CH:14]=[C:11]2[N:12]([CH:2]=1)[CH:13]=[C:8]([C:6]#[N:7])[CH:9]=[CH:10]2

Komponenten

5

Edukt 2

HCID 11715BromoacetoneHCID 2819956-Methylpyridine-3-carbonitrile

Produkt 1

HCID 5933682-Methylindolizine-6-carbonitrileAusbeute 84 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8857Ethyl AcetateLösungsmittelHCID 31347SulfolaneLösungsmittel

Reaktionsbedingungen

Temperatur
45 °C

Versuchsvorschrift

1-Bromo-propan-2-one (2.26 ml) is added under an atmosphere of argon to a solution of 5-cyano-2-methylpyridine (5.0 g, 41.9 mmol) in sulfolane (30 ml). The reaction mixture is stirred for 48 hours at 45° C., then diluted with EtOAc. The precipitated salt is filtered off and dissolved in water (50 ml). The aqueous solution is washed with EtOAc, then a 10% aqueous solution of NaHCO3 (30 ml) is added, and the mixture is heated to reflux for 1 hour. After cooling, the reaction mixture is filtered, and the filtrate is extracted three times with EtOAc. The combined organic layers are dried over Na2SO4, filtered, and concentrated in vacuo. The residue is purified via flash chromatography (hexane/EtOAc 8:1, +0.2% NEt3) to afford the title compound (5.50 g, 84%). 1H NMR (400 MHz, d6-DMSO): δ=9.10-9.09 (m, 1H), 7.59 (s, 1H), 7.55 (d, J=9.0 Hz, 1H), 6.90 (dd, J=9.3/1.7 Hz, 1H), 6.55 (s, 1H), 2.39 (s, 3H). MS (ES+): 157 (M+H)+.

Aufarbeitung

  1. filtrationThe precipitated salt is filtered off
  2. dissolutiondissolved in water (50 ml)
  3. washThe aqueous solution is washed with EtOAc
  4. additiona 10% aqueous solution of NaHCO3 (30 ml) is added
  5. temperaturethe mixture is heated
  6. temperatureto reflux for 1 hour
  7. temperatureAfter cooling
  8. filtrationthe reaction mixture is filtered
  9. extractionthe filtrate is extracted three times with EtOAc
  10. dry with materialThe combined organic layers are dried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe residue is purified via flash chromatography (hexane/EtOAc 8:1, +0.2% NEt3)

Quellen und Nachweise

ORD-Eintrag
ord-2e18701dd2f74d6693b39c1b7977faf9
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08742132B2

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