Citric Acid → methyl 1-(biphenyl-4-ylmethyl)-1H-indole-7-carboxylate

HRID 1909882Notes

Reaction equation

HRID 1909882 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[C:10]([O:12][CH3:13])=[O:11])[CH:3]=[CH:2]1.CC(C)([O-])C.[K+].Br[CH2:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[CH:24][CH:23]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C>[C:25]1([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:24]=[CH:23][C:22]([CH2:21][N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][C:8]=3[C:10]([O:12][CH3:13])=[O:11])[CH:3]=[CH:2]2)=[CH:27][CH:26]=1

Participants

6

Reactant 4

HCID 311Citric AcidHCID 2577161,1'-Biphenyl, 4-(bromomethyl)-HCID 676694Methyl indole-7-carboxylateHCID 23665647Potassium tert-butoxide

Product 1

HCID 58306447methyl 1-(biphenyl-4-ylmethyl)-1H-indole-7-carboxylateYield 85.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To methyl 1H-indole-7-carboxylate (1.5 g) was added DMF (15 mL), and potassium tert-butoxide (1.5 g) was added thereto under ice-cooling, followed by stirring for 10 minutes. 4-(Bromomethyl)biphenyl (2.8 g) was added thereto, followed by stirring at room temperature for 19 hours. The reaction mixture was again ice-cooled, and a 10% aqueous citric acid solution (20 mL) was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=97/3-95/5) to obtain methyl 1-(biphenyl-4-ylmethyl)-1H-indole-7-carboxylate (2.5 g).

Workup

  1. additionwas added
  2. temperatureunder ice-cooling
  3. stirringby stirring at room temperature for 19 hours
  4. temperaturecooled
  5. extractionfollowed by extraction with ethyl acetate
  6. washThe organic layer was washed with saturated brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=97/3-95/5)

Sources & evidence

ORD record
ord-f9d7aff4fdae4c36aecc30e87435c9da
Source dataset
uspto-grants-2013_12
Patent number
US08598355B2

Reaction notes

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