Ethyl 3-phenylprop-2-enoate → 3-(3-cyano-1H-Indol-4-yl)-3-phenyl-acrylic acid ethyl ester

HRID 1716664Notes

Reaction equation

HRID 1716664 reaction equation
Br[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]([C:11]#[N:12])=[CH:5][NH:6]2.[C:13]([O:23][CH2:24][CH3:25])(=[O:22])[CH:14]=[CH:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH2:24]([O:23][C:13](=[O:22])[CH:14]=[C:15]([C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]([C:11]#[N:12])=[CH:5][NH:6]2)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH3:25]

Participants

4

Reactant 2

HCID 7649Ethyl 3-phenylprop-2-enoateHCID 27632324-Bromo-1H-indole-3-carbonitrile

Product 1

HCID 673553223-(3-cyano-1H-Indol-4-yl)-3-phenyl-acrylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 74236Tetrabutylammonium BromideCatalyst

Conditions

Temperature
110 °C

Procedure

A mixture of 4-bromo-1H-indole-3-carbonitrile LVII (2 g, 9.05 mmol), ethyl cinnamate (3.19 g, 18.1 mmol), tetrabutylammonium bromide (582 mg, 1.81 mmol), TEA (2.52 ml, 18.1 mmol) and palladium-dichloro-[bis-(tri-ortho-tolyl)phosphine] (357 mg, 0.453 mmol) in a sealed vial was stirred at 110° C. for 20 hours. The reaction mixture was cooled to room temperature, partitioned between H2O and DCM, and the aqueous layer was extracted with DCM. The organic extracts were combined, dried over Na2SO4, filtered, concentrated, and purified via flash chromatography (hexane/EtOAc) affording 3-(3-cyano-1H-Indol-4-yl)-3-phenyl-acrylic acid ethyl ester LVIII as a yellow solid (1.57 g, 55% yield).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. custompartitioned between H2O and DCM
  3. extractionthe aqueous layer was extracted with DCM
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified via flash chromatography (hexane/EtOAc)

Sources & evidence

ORD record
ord-e579b51b79374a94bcf017ab3d6e8170
Source dataset
uspto-grants-2010_09
Patent number
US07803830B2

Reaction notes

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