Ethanol → 6-fluoro-5-[4-(hydroxymethyl)phenyl]-1H-indole-3-carbaldehyde

HRID 1054576Notes

Reaction equation

HRID 1054576 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[F: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)C.C(=O)([O-])[O-].[K+].[K+]>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].C1(C)C=CC=CC=1>[F: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

Participants

7

Reactant 4

HCID 702EthanolHCID 11430Potassium CarbonateHCID 27347064-(Hydroxymethyl)benzeneboronic acidHCID 735543615-Bromo-6-fluoro-1H-indole-3-carbaldehyde

Product 1

HCID 866985806-fluoro-5-[4-(hydroxymethyl)phenyl]-1H-indole-3-carbaldehydeYield 58.4%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 5-bromo-6-fluoro-1H-indole-3-carbaldehyde (100 mg, 0.413 mmol), [4-(hydroxymethyl)phenyl]boronic acid (69 mg, 0.454 mmol), ethanol (1.04 mL), toluene (1.0 mL) and 2 M aqueous potassium carbonate (0.824 mL, 1.65 mmol) were deoxygenated with nitrogen. [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium (II) (25 mg, 0.033 mmol) was added and the reaction mixture was deoxygenated with nitrogen for 2 more minutes. The reaction mixture was sealed and heated at 90° C. for 16 hours. After cooling to room temperature, the phases were separated, and the aqueous phase was diluted with water and extracted twice with ethyl acetate. The combined organic layers were concentrated in vacuo and purified using silica gel chromatography (1:3 to 3:1 ethyl acetate/heptanes) to give the title compound (65 mg). MS (ES−) 268.2 (M−H)−.

Workup

  1. customwere deoxygenated with nitrogen
  2. customthe reaction mixture was deoxygenated with nitrogen for 2 more minutes
  3. customThe reaction mixture was sealed
  4. temperatureAfter cooling to room temperature
  5. customthe phases were separated
  6. additionthe aqueous phase was diluted with water
  7. extractionextracted twice with ethyl acetate
  8. concentrationThe combined organic layers were concentrated in vacuo
  9. custompurified

Sources & evidence

ORD record
ord-b057b958f4a04a61a02376d1db4ec391
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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