Acetic Acid → Ethyl 6-chloroindole-2-carboxylate

HRID 603939Notes

Reaction equation

HRID 603939 reaction equation
[CH2:1]([O:3][C:4](=[O:18])[C:5](=O)[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][C:8]=1[N+:14]([O-])=O)[CH3:2].CC(O)=O>C(O)C.ClCCl.[Fe]>[CH2:1]([O:3][C:4]([C:5]1[NH:14][C:8]2[C:7]([CH:6]=1)=[CH:12][CH:11]=[C:10]([Cl:13])[CH:9]=2)=[O:18])[CH3:2]

Participants

6

Reactant 2

HCID 176Acetic AcidHCID 11173303Ethyl 3-(4-chloro-2-nitrophenyl)-2-oxopropanoate

Product 1

HCID 7015027Ethyl 6-chloroindole-2-carboxylate

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

To crude 3-(4-chloro-2-nitro-phenyl)-2-oxo-propionic acid ethyl ester (151 mmol) in ethanol:glacial HOAc (1:1, v/v, 560 mL) at rt was added iron powder (74.4 g) and the reaction mixture was stirred at reflux for 4 h. The mixture was filtered and evaporated to give a residue which was redistributed in dichloromethane/1N HCl. The organic layer was washed with 1N HCl, NaHCO3, and brine and dried. Evaporation followed by crystallization (DCM) gave 6-Chloro-1H-indole-2-carboxylic acid ethyl ester as a pale yellow solid (16.8 g, 50% over 2 steps).

Workup

  1. temperatureat reflux for 4 h
  2. filtrationThe mixture was filtered
  3. customevaporated
  4. customto give a residue which
  5. washThe organic layer was washed with 1N HCl, NaHCO3, and brine
  6. customdried
  7. customEvaporation
  8. customfollowed by crystallization (DCM)

Sources & evidence

ORD record
ord-6b67dc4938034cd990f3c829fc8d756e
Source dataset
uspto-grants-2011_03
Patent number
US07906548B2

Reaction notes

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