P-Toluenesulfonylhydrazide → Ethyl 1-cyclopropyl-3-methyl-4-methoxy-1H-indole-6-carboxylate

HRID 420145Notes

Reaction equation

HRID 420145 reaction equation
[CH:1]1([N:4]2[C:12]3[C:7](=[C:8]([O:18][CH3:19])[CH:9]=[C:10]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH:11]=3)[C:6]([CH:20]=O)=[CH:5]2)[CH2:3][CH2:2]1.S(NN)(C1C=CC(C)=CC=1)(=O)=O>CCO>[CH:1]1([N:4]2[C:12]3[C:7](=[C:8]([O:18][CH3:19])[CH:9]=[C:10]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH:11]=3)[C:6]([CH3:20])=[CH:5]2)[CH2:2][CH2:3]1

Participants

4

Reactant 2

HCID 15303P-ToluenesulfonylhydrazideHCID 86621575ethyl 1-cyclopropyl-3-formyl-4-methoxy-1H-indole-6-carboxylate

Product 1

HCID 66649525Ethyl 1-cyclopropyl-3-methyl-4-methoxy-1H-indole-6-carboxylateYield 88.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a stirred solution of 3.30 g of ethyl 1-cyclopropyl-3-formyl-4-methoxy-1H-indole-6-carboxylate in 33 ml of EtOH was added 2.57 g of TsNHNH2 and the mixture was refluxed for 30 min. After evaporation of EtOH, the mixture was diluted with 28 ml of DMF and 28 ml of sulfolane, then 2.89 g of NaBH3CN and 0.57 g of TsOH H2O was added thereto successively. The mixture was refluxed for 30 min and cooled to room temperature. After diluted with Et2O, the mixture was washed successively with water, saturated NaHCO3aq, and saturated brine, dried over Na2SO4, concentrated. The residue was purified on SiO2 column chromatography (EtOAc/n-hexane system) to give 2.78 g of Ethyl 1-cyclopropyl-3-methyl-4-methoxy-1H-indole-6-carboxylate as a colorless powder.

Workup

  1. temperaturethe mixture was refluxed for 30 min
  2. customAfter evaporation of EtOH
  3. additionthe mixture was diluted with 28 ml of DMF and 28 ml of sulfolane
  4. addition2.89 g of NaBH3CN and 0.57 g of TsOH H2O was added
  5. temperatureThe mixture was refluxed for 30 min
  6. additionAfter diluted with Et2O
  7. washthe mixture was washed successively with water, saturated NaHCO3aq, and saturated brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated
  10. customThe residue was purified on SiO2 column chromatography (EtOAc/n-hexane system)

Sources & evidence

ORD record
ord-138a66f5b527496497f505dc3dc323fa
Source dataset
uspto-grants-2012_01
Patent number
US08093389B2

Reaction notes

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