Dimethylformamide → 7-bromo-5-chloro-1H-indole-3-carbaldehyde

HRID 913964

Reaktionsgleichung

Reaktionsgleichung von HRID 913964
P(Cl)(Cl)(Cl)=O.[Br:6][C:7]1[CH:8]=[C:9]([Cl:16])[CH:10]=[C:11]2[C:15]=1[NH:14][CH:13]=[CH:12]2.CN([CH:20]=[O:21])C>>[Br:6][C:7]1[CH:8]=[C:9]([Cl:16])[CH:10]=[C:11]2[C:15]=1[NH:14][CH:13]=[C:12]2[CH:20]=[O:21]

Komponenten

4

Edukt 3

HCID 6228Dimethylformamide2×HCID 24813Phosphorus oxychlorideHCID 247295047-bromo-5-chloro-1H-indole

Produkt 1

HCID 575461137-bromo-5-chloro-1H-indole-3-carbaldehydeAusbeute 82 %

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Phosphorus oxychloride (3.11 mL, 33.4 mmol) was added dropwise to a 0° C sample of DMF (30 mL). The reaction was stirred 30 min at 0° C., then 7-bromo-5-chloro-1H-indole (7.0 g, 30.4 mmol) in DMF (5 mL)was added and the reaction was warmed to ambient temperature and stirred 20 hours. Ice water (300 mL) was added, and the resulting thick solid was filtered. The product was detected by TLC in both filtrate and cake. Cake and filtrate were combined, and sodium hydroxide (10N) was added until most solids disappeared, then the mixture was extracted with ethyl acetate (4×100 mL). The organic layers were dried with MgSO4 and evaporated to a solid that weighed 10.5 g. The residue was dissolved in 400 mL boiling ethyl acetate, the insoluble material was filtered away and the filtrate was evaporated. 7-bromo-5-chloro-1H-indole-3-carbaldehyde (6.45 g, 24.95 mmol, 82% yield) was obtained as an off-white solid. 1H-NMR (CDCl3, 400 MHz) δ 9.99 (s, 1H), 8.35 (s, 1H), 8.32 (s, 1H), 7.92 (s, 1H), 7.47 (d, J=2.0 Hz, 1H). LC/MS (HPLC method 4): tR=2.87 min, 257.91(MH)+.

Aufarbeitung

  1. temperaturethe reaction was warmed to ambient temperature
  2. stirringstirred 20 hours
  3. filtrationthe resulting thick solid was filtered
  4. additionsodium hydroxide (10N) was added until most solids
  5. extractionthe mixture was extracted with ethyl acetate (4×100 mL)
  6. dry with materialThe organic layers were dried with MgSO4
  7. customevaporated to a solid that
  8. dissolutionThe residue was dissolved in 400 mL
  9. filtrationthe insoluble material was filtered away
  10. customthe filtrate was evaporated

Quellen und Nachweise

ORD-Eintrag
ord-e8ac9ee96e52429c9f40f89914f50e29
Quelldatensatz
uspto-grants-2011_09
Patentnummer
US08026257B2

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