Acetic Acid → Methyl indole-6-carboxylate

HRID 853720Notes

Reaction equation

HRID 853720 reaction equation
[C:1](O)(=O)C.O.C1(C)C=CC=CC=1.[CH3:13][C:14]1[CH:23]=[CH:22][C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:16][C:15]=1[N+:24]([O-])=O>CN(C=O)C.[Fe].C1CCCCC1>[NH:24]1[C:15]2[C:14](=[CH:23][CH:22]=[C:17]([C:18]([O:20][CH3:21])=[O:19])[CH:16]=2)[CH:13]=[CH:1]1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 962WaterHCID 1140TolueneHCID 81816Methyl 4-methyl-3-nitrobenzoate

Product 1

HCID 639844Methyl indole-6-carboxylateYield 80%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 6228DimethylformamideSolventHCID 8078CyclohexaneSolvent

Conditions

Temperature
80 °C

Procedure

Into a reaction flask were introduced 176.4 g of iron powder, 43.5 g of acetic acid, 71.2 g of water and 273.3 g of toluene. The content of the flask was heated to 80° C. Then, a solution of 131.8 g of methyl 4-methyl-3-nitrobenzoate in 110.4 g of DMF was dropwise added into the above-mentioned mixed solution over a period of about one hour, after which the resulting mixture was stirred for an additional 4 hours at 80° C. After cooling the reaction mixture, the solid material was removed by filtration. The filtrate was washed with 5% aqueous solution of NaOH, and washed with 5% aqueous solution of hydrochloric acid and water, and then the toluene was distilled off to obtain a brown-colored solid product. Then, 164.3 g of cyclohexane was added to dissolve the solid product at about 80° C. The resulting solution was cooled to room temperature, and the deposited crystalline material was collected by filtration and dried to obtain 73.8 g (yield 80.0%) of methyl indole-6-carboxylate monomer.

Workup

  1. temperatureAfter cooling the reaction mixture
  2. customthe solid material was removed by filtration
  3. washThe filtrate was washed with 5% aqueous solution of NaOH
  4. washwashed with 5% aqueous solution of hydrochloric acid and water
  5. distillationthe toluene was distilled off
  6. customto obtain a brown-colored solid product
  7. dissolutionto dissolve the solid product at about 80° C
  8. temperatureThe resulting solution was cooled to room temperature
  9. filtrationthe deposited crystalline material was collected by filtration
  10. customdried

Sources & evidence

ORD record
ord-32e26a04ef3241fe8b6944d93fc82fca
Source dataset
uspto-grants-2007_08
Patent number
US07255779B2

Reaction notes

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