Potassium Carbonate → 1h-Indole-5-carboxylic acid,3-methyl-2-phenyl-,ethyl ester

HRID 723633Notes

Reaction equation

HRID 723633 reaction equation
[NH2:1][C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][C:3]=1I.[Li+].[Cl-].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[K+].[K+].[C:41]1([C:47]#[C:48][CH3:49])[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1>CN(C=O)C.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:41]1([C:47]2[NH:1][C:2]3[C:3]([C:48]=2[CH3:49])=[CH:4][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:11][CH:12]=3)[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1

Participants

9

Reactant 5

HCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 69601MethylphenylacetyleneHCID 433294Lithium ChlorideHCID 459320Ethyl 4-amino-3-iodobenzoate

Product 1

HCID 218745001h-Indole-5-carboxylic acid,3-methyl-2-phenyl-,ethyl esterYield 57.2%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Adapting the procedure of H.-C. Zhang (Tet. Lett. 1997, 38, 2439) ethyl 4-amino-3-iodobenzoate (from example 10, 0.500 g, 1.72 mmol) was dissolved in DMF (5 mL) and LiCl (0.073 g, 1.72 mmol, 1 equivalent), PPh3 (0.090 g, 0.34 mmol, 0.2 equivalent), K2CO3 (1.188 g, 8.6 mmol, 5 equivalents) and phenylpropyne (0.645 mL, 5.76 mmol, 3 equivalents) were added. The solution was degassed by purging with argon for 1 h and palladium acetate (0.039 g, 0.17 mmol, 0.1 equivalent) was added. The mixture was stirred at 80° C. under argon for 20 h. The reaction mixture was diluted with water (25 mL) and extracted with EtOAc (50 mL). The extract was washed with brine (3×25 mL) and dried (MgSO4). Concentration under reduced pressure and purification by flash chromatography with 10–15% EtOAc-hexane gave the desired 2-phenyl-3-methyl indole (0.275 g, least polar component) and the 3-phenyl-2-methyl isomer (0.109 g, more polar component).

Workup

  1. customThe solution was degassed
  2. customby purging with argon for 1 h
  3. extractionextracted with EtOAc (50 mL)
  4. washThe extract was washed with brine (3×25 mL)
  5. dry with materialdried (MgSO4)
  6. concentrationConcentration
  7. customunder reduced pressure and purification by flash chromatography with 10–15% EtOAc-hexane

Sources & evidence

ORD record
ord-9bb1f289a13d4bbf8f85985e11340eb2
Source dataset
uspto-grants-2006_11
Patent number
US07141574B2

Reaction notes

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