Water → 5-Methoxyoxindole

HRID 1937570Notes

Reaction equation

HRID 1937570 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[C:6]2=O.O.NN.O>C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH2:6]2

Participants

5

Reactant 3

HCID 962WaterHCID 24654Hydrazine hydrate (1:1)HCID 383335-Methoxyisatin

Product 1

HCID 15142865-MethoxyoxindoleYield 15.2%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

5-Methoxyisatin (5.0 g) and 30 mL hydrazine hydrate were heated to reflux for 15 minutes. The reaction mixture was cooled to room temperature and 50 mL water was added. The mixture was extracted 3 times with 25 mL of ethyl acetate, the organic layers were combined, dried over anhydrous sodium sulfate and concentrated to give a yellow solid. The solid was stirred in ethyl acetate and 1.1 g of insoluble material removed by vacuum filtration and saved. This material proved to be 2-hydrazinocarbonylmethyl-4-anisidine. The filtrate was concentrated and chromatographed on silica gel eluting with ethyl acetate:hexane 1:1 to give 0.7 g of 5-methoxy-2-oxindole as a dirty yellow solid. The 1.1 g of 2-hydrazinocarbonylmethyl-4-anisidine was refluxed for 1 hour in 20 mL of 1 N sodium hydroxide. The mixture was cooled, acidified to pH 2 with concentrated hydrochloric acid and extracted 3 times with 25 mL of ethyl acetate. The organic extracts were combined, washed with brine, dried over anhydrous sodium sulfate and concentrated to give 0.8 g of 5-methoxy-2-oxindole as a dirty yellow solid. The combined yield was 1.5 g or 33%.

Workup

  1. temperatureto reflux for 15 minutes
  2. extractionThe mixture was extracted 3 times with 25 mL of ethyl acetate
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated
  5. customto give a yellow solid
  6. custom1.1 g of insoluble material removed by vacuum filtration
  7. concentrationThe filtrate was concentrated
  8. customchromatographed on silica gel eluting with ethyl acetate:hexane 1:1

Sources & evidence

ORD record
ord-f175346f8c914dc0a7e84880f4f3af56
Source dataset
uspto-grants-2002_05
Patent number
US06395734B1

Reaction notes

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