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

HRID 338298Notes

Reaction equation

HRID 338298 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].C(=O)([O-])[O-].[K+].[K+].CC1(C)COB([C:28]2[CH:38]=[CH:37][C:31]([O:32][CH2:33][CH2:34][CH2:35][OH:36])=[CH:30][CH:29]=2)OC1>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:28]2[CH:38]=[CH:37][C:31]([O:32][CH2:33][CH2:34][CH2:35][OH:36])=[CH:30][CH:29]=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

5

Reactant 3

HCID 11430Potassium CarbonateHCID 866985785-Bromo-4,6-difluoro-1H-indole-3-carbaldehydeHCID 866986443-(4-(5,5-Dimethyl-1,3,2-dioxaborinan-2-yl)phenoxy)propan-1-ol

Product 1

HCID 866986434,6-difluoro-5-[4-(3-hydroxypropoxy)phenyl]-1H-indole-3-carbaldehydeYield 20%

Reagents, catalysts & solvents 1

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

Procedure

To the slurry of 5-bromo-4,6-difluoro-1H-indole-3-carbaldehyde was added 2M potassium carbonate (0.7 mL) and the mixture was stirred at room temperature for 5 min. Then 3-(4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenoxy)propan-1-ol (120 mg, 0.46 mmol) and Pd(dppf)Cl2 (20 mg) was added to the reaction. The reaction was heated to 90° C. for 30 min. Solvent was removed under reduced pressure to give a residue, which was purified by silica gel chromatography (petroleum ether/ethyl acetate=4:1) to give the title compound (30 mg, 20%) as a yellow solid.

Workup

  1. temperatureThe reaction was heated to 90° C. for 30 min
  2. customSolvent was removed under reduced pressure
  3. customto give a residue, which
  4. customwas purified by silica gel chromatography (petroleum ether/ethyl acetate=4:1)

Sources & evidence

ORD record
ord-24cb6a2cd09441bbbcbde4fb484c40ce
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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