Potassium Carbonate → 6-Chloro-5-(4-hydroxymethyl-phenyl)-1H-indole-3-carbaldehyde

HRID 338219

Reaktionsgleichung

Reaktionsgleichung von HRID 338219
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[Cl:11])[NH:7][CH:6]=[C:5]2[CH:12]=[O:13].[OH:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19](B(O)O)=[CH:18][CH:17]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.CCO.CCOC(C)=O.CCOC(C)=O.CCCCCCC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:11][C:10]1[CH:9]=[C:8]2[C:4]([C:5]([CH:12]=[O:13])=[CH:6][NH:7]2)=[CH:3][C:2]=1[C:19]1[CH:20]=[CH:21][C:16]([CH2:15][OH:14])=[CH:17][CH:18]=1

Komponenten

9

Edukt 3

HCID 11430Potassium CarbonateHCID 27347064-(Hydroxymethyl)benzeneboronic acidHCID 866985665-bromo-6-chloro-1H-indole-3-carbaldehyde

Produkt 1

HCID 866985706-Chloro-5-(4-hydroxymethyl-phenyl)-1H-indole-3-carbaldehydeAusbeute 20 %

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 702EthanolLösungsmittelHCID 1140TolueneLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 21899848Ethylacetate heptaneLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

A mixture of 5-bromo-6-chloro-1H-indole-3-carbaldehyde (783 mg, 3.03 mmol), 4-(hydroxymethyl)benzene boronic acid (460 mg, 3.03 mmol), 2N aqueous potassium carbonate (6.4 mL, 13 mmol) in toluene (9 mL) and EtOH (13 mL) was degassed with N2 for 5 minutes, then treated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (247 mg, 0.30 mmol). The mixture was heated in a sealed tube to 120° C. and stirred for 2.5 hours. The reaction mixture was cooled to room temperature, diluted with EtOAc (200 mL), then washed with water (50 mL) and brine (50 mL). The organic layer was dried over MgSO4 and concentrated in vacuo. The resulting brown foam was purified by flash chromatography (20-100% EtOAc/heptane) to afford a pale yellow solid. The solid was dissolved in 5:1 EtOAc/heptane (30 mL), and a colorless precipitate formed. The precipitate was collected by filtration, washed with heptane and dried under vacuum to afford the title compound (173 mg, 20% yield) as a colorless solid. MS (ES+) 286.0 (M+H)+. 1H NMR (500 MHz, CD3OD) δ 9.92 (s, 1H) 8.07 (s, 1H) 8.25 (s, 1H) 7.64 (s, 1H) 7.44 (m, 4H) 4.70 (s, 2H).

Aufarbeitung

  1. customwas degassed with N2 for 5 minutes
  2. temperatureThe reaction mixture was cooled to room temperature
  3. washwashed with water (50 mL) and brine (50 mL)
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe resulting brown foam was purified by flash chromatography (20-100% EtOAc/heptane)
  7. customto afford a pale yellow solid
  8. customa colorless precipitate formed
  9. filtrationThe precipitate was collected by filtration
  10. washwashed with heptane
  11. customdried under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-f76aa54d9f294fed941559c9d9058359
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08889730B2

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