Ethyl Acetate → 1-tert-Butoxycarbonylmethyl-1H-indole-3-carboxylic acid ethyl ester

HRID 1527206Notes

Reaction equation

HRID 1527206 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[NH:8][CH:7]=1)=[O:5])[CH3:2].C(=O)([O-])[O-].[K+].[K+].Br[CH2:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24].CCOC(C)=O>CC#N.O>[CH2:1]([O:3][C:4]([C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[N:8]([CH2:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH:7]=1)=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 79177tert-Butyl bromoacetateHCID 247965Ethyl Indole-3-carboxylate

Product 1

HCID 682832491-tert-Butoxycarbonylmethyl-1H-indole-3-carboxylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a suspension of 1H-indole-3-carboxylic acid ethyl ester (800 mg, 4.23 mmol) and potassium carbonate (1.34 g, 9.72 mmol) in CH3CN (21 mL) under nitrogen was added tert-butyl bromoacetate (875 μL, 5.92 mmol) and the reaction mixture was heated at reflux overnight. The reaction mixture was allowed to cool to RT, EtOAc and water were added and the layers were separated, the aqueous one being re-extracted with EtOAc. The organic layers were washed with brine, dried (Na2SO4), filtered and concentrated. The crude residue was purified by flash column chromatography (c-hexane to c-hexane/EtOAc 1:1) to afford the desired compound. TLC, Rf (EtOAc)=0.77; MS (LC/MS): 304.1 [M+H]+, 302.0 [M−H]−; tR (HPLC conditions a): 4.01 min.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux overnight
  3. customthe layers were separated
  4. extractionthe aqueous one being re-extracted with EtOAc
  5. washThe organic layers were washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude residue was purified by flash column chromatography (c-hexane to c-hexane/EtOAc 1:1)

Sources & evidence

ORD record
ord-fae24d65a5f2472a802ca4c0dd96faf7
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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