Hydrazine hydrate (1:1) → 4-Methoxy-2-indolinone

HRID 2416930Notes

Reaction equation

HRID 2416930 reaction equation
O.NN.[CH3:4][O:5][C:6]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:7]=1[C:8](=O)[C:9](=[O:15])[NH:10]2.C([O-])(=O)C.[Na+]>CN(C)C=O>[CH3:4][O:5][C:6]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:7]=1[CH2:8][C:9](=[O:15])[NH:10]2

Participants

5

Reactant 3

HCID 24654Hydrazine hydrate (1:1)HCID 517045Sodium AcetateHCID 113788194-methoxy-2,3-dihydro-1H-indole-2,3-dione

Product 1

HCID 5960014-Methoxy-2-indolinoneYield 79.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

Hydrazine monohydrate (265 mL, 5.46 mol) is added to a flask containing 4-methoxyisatin (484.26 g, 2.73 mol), sodium acetate (22.31 g, 0.27 mol) and dimethylformamide (2.4 L). The temperature rose from 19.2° C. to 31.9° C. within 5 minutes, and when the exotherm had ceased the solution is further heated to 110° C. over 40 minutes. Vigorous off-gassing is observed, and the temperature rose above the set point slowly. After 30 minutes the temperature stabilized at 110° C. and the gas evolution tapered off. The solution is kept at 110° C. for 40.5 hours at which point the heating mantle is removed and the solution is allowed to cool. At 40° C., the solution is seeded with 100 mg of 4-methoxyindole, and the contents are cooled to 17° C. with an ice bath. The resulting mixture is poured into water (6.2 L) which had been pre-cooled to 6° C. The flask is rinsed with water (600 mL), and the thick slurry is cooled to 4° C. before being filtered through polypropylene. The filter cake is rinsed with water (3×1.5 L) and the solid is dried in a 50° C. vacuum oven to provide 353 g of 4-methoxyindolin-2-one.

Workup

  1. waitAfter 30 minutes the temperature stabilized at 110° C.
  2. waitThe solution is kept at 110° C. for 40.5 hours at which point
  3. customthe heating mantle is removed
  4. temperatureto cool
  5. customAt 40° C.
  6. temperaturethe contents are cooled to 17° C. with an ice bath
  7. additionThe resulting mixture is poured into water (6.2 L) which
  8. temperaturehad been pre-cooled to 6° C
  9. washThe flask is rinsed with water (600 mL)
  10. temperaturethe thick slurry is cooled to 4° C.
  11. filtrationbefore being filtered through polypropylene
  12. washThe filter cake is rinsed with water (3×1.5 L)
  13. customthe solid is dried in a 50° C. vacuum oven

Sources & evidence

ORD record
ord-04653e9cdd124cd09521089b426941ec
Source dataset
uspto-grants-2004_11
Patent number
US06825220B2

Reaction notes

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