Potassium Carbonate → 6-chloro-5-{4-[1-(hydroxymethyl)cyclobutyl]phenyl}-1H-indole-3-carbaldehyde

HRID 338397

Reaktionsgleichung

Reaktionsgleichung von HRID 338397
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][C:3]=1B1OCC(C)(C)CO1.[C:19](=O)([O-])[O-:20].[K+].[K+].Br[C:26]1[CH:31]=[CH:30][C:29]([C:32]2([CH2:36][OH:37])[CH2:35][CH2:34][CH2:33]2)=[CH:28][CH:27]=1>O1CCOCC1.CN(C=O)C.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:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:19]=[O:20])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:26]1[CH:31]=[CH:30][C:29]([C:32]2([CH2:36][OH:37])[CH2:35][CH2:34][CH2:33]2)=[CH:28][CH:27]=1

Komponenten

7

Edukt 3

HCID 11430Potassium CarbonateHCID 58538689(1-(4-Bromophenyl)cyclobutyl)methanolHCID 866987336-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole

Produkt 1

HCID 866987376-chloro-5-{4-[1-(hydroxymethyl)cyclobutyl]phenyl}-1H-indole-3-carbaldehydeAusbeute 68 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 6228DimethylformamideLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

A mixture of 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole (260 mg, 1.00 mmol) and N,N-dimethylformiminium chloride (250 mg, 2.00 mmol) in dry dioxane (5 mL) and DMF (1 mL) was sealed in a reaction vessel and stirred at room temperature for 10 minutes to give a white slurry. To the slurry was added 2M aqueous potassium carbonate (2.5 mL, 5.0 mmol), [1-(4-bromophenyl)cyclobutyl]methanol (240 mg, 1.00 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (50 mg). The reaction mixture was degassed with nitrogen and heated to 90° C. for 30 minutes. The reaction was quenched with water (20 mL) and extracted with EtOAc (3×20 mL). The combined organic phases were dried and concentrated in vacuo to give 6-chloro-5-{4-[1-(hydroxymethyl)cyclobutyl]phenyl}-1H-indole-3-carbaldehyde (180 mg, 68% yield), which was used into next step without further purification.

Aufarbeitung

  1. customwas sealed in a reaction vessel
  2. customto give a white slurry
  3. customThe reaction mixture was degassed with nitrogen
  4. temperatureheated to 90° C. for 30 minutes
  5. customThe reaction was quenched with water (20 mL)
  6. extractionextracted with EtOAc (3×20 mL)
  7. customThe combined organic phases were dried
  8. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-84ae9c62db7c40049adc7ab9d4f73573
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08889730B2

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