Potassium Carbonate → 4,6-difluoro-5-[4-(2-hydroxyethoxy)phenyl]-1H-indole-3-carbaldehyde

HRID 338287Notes

Reaction equation

HRID 338287 reaction equation
Br[C:2]1[C:3]([F:14])=[C:4]2[C:8](=[CH:9][C:10]=1[F:11])[NH:7][CH:6]=[C:5]2[CH:12]=[O:13].CC1(C)COB([C:22]2[CH:31]=[CH:30][C:25]([O:26][CH2:27][CH2:28][OH:29])=[CH:24][CH:23]=2)OC1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.CCO.O.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]>[F:14][C:3]1[C:2]([C:22]2[CH:31]=[CH:30][C:25]([O:26][CH2:27][CH2:28][OH:29])=[CH:24][CH:23]=2)=[C:10]([F:11])[CH:9]=[C:8]2[C:4]=1[C:5]([CH:12]=[O:13])=[CH:6][NH:7]2

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 866985785-Bromo-4,6-difluoro-1H-indole-3-carbaldehydeHCID 866986342-[4-(5,5-Dimethyl-1,3,2-dioxaborinan-2-yl)phenoxy]ethanol

Product 1

HCID 866986334,6-difluoro-5-[4-(2-hydroxyethoxy)phenyl]-1H-indole-3-carbaldehydeYield 38%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A solution of 5-bromo-4,6-difluoro-1H-indole-3-carbaldehyde (150 mg, 0.58 mmol) and 2-[4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenoxy]ethanol (158 mg, 0.64 mmol) in toluene (5 mL) and EtOH (1.6 mL) was added to a solution of potassium carbonate (240 mg, 1.74 mmol) in water (1.2 mL) and Pd(dppf)Cl2 (24 mg, 0.029 mmol) at room temperature under N2. TLC (petroleum ether/EtOAc=1:1) showed the reaction was complete. The reaction was cooled to room temperature, and extracted with ethyl acetate (20 mL×2). The organic layers were washed with brine (10 mL), dried over sodium sulfate, concentrated in vacuo, and purified by column chromatography to give the title compound (70 mg, 38%) as a yellow solid.

Workup

  1. extractionextracted with ethyl acetate (20 mL×2)
  2. washThe organic layers were washed with brine (10 mL)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. custompurified by column chromatography

Sources & evidence

ORD record
ord-53d67ec629ce4d348e80bb588c85104c
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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