Hydrazine hydrate (1:1) → 1-benzyl-1,3-dihydro-2H-indol-2-one

HRID 2383627Notes

Reaction equation

HRID 2383627 reaction equation
[CH2:1]([N:8]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:11](=O)[C:9]1=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.NN>CCOCC.CCCCC>[CH2:1]([N:8]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH2:11][C:9]1=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 2647341-Benzylisatin

Product 1

HCID 117908211-benzyl-1,3-dihydro-2H-indol-2-oneYield 78.2%

Reagents, catalysts & solvents 1

HCID 21877078Diethylether pentaneSolvent

Conditions

Temperature
125 °C

Procedure

Prepared according to literature procedure (C. Martin and E. M. Carreira, J. Am. Chem. Soc., 2005, 127, 11505-11515). A stirred solution of isatin (10.0 g, 68 mmol) in dry DMF (125 mL) was cooled in an ice bath before addition of sodium hydride (60 wt % in mineral oil, 2.86 g, 71.5 mmol) in 10 portions, the orange solution turning quickly purple. When no further evolution of gas was observed, benzyl bromide (13.4 g, 78.0 mmol) was added by syringe. A colour change back to orange was observed within 20 min Water (300 mL) was added with stirring, and the resulting orange-red precipitate collected by filtration and washed with water and a little cold ethanol. The solid was then recrystallized from boiling ethanol (300 mL) to afford N-benzylisatin (13.7 g, 85%) as long, red needles. N-benzylisatin (13.0 g, 55 mmol) was mixed with hydrazine hydrate (60 mL) and placed in an oil bath. The mixture was heated in stages to 125° C., becoming first a green sludge, then yellow with clumps of a sticky solid. After a total of 5 h at 125° C., the mixture was cooled and extracted with EtOAc (2×100 mL). The combined organic portions were washed twice with 1.0 M aq. H2SO4, and once each with half-saturated brine then brine, dried over MgSO4, filtered and concentrated to afford a pale yellow solid. Re-precipitation from ether/pentane gave the title compound as an off-white solid (9.6 g, 75%). Spectral data matches literature values (C. Martin and E. M. Carreira, J. Am. Chem. Soc., 2005, 127, 11505-11515).

Workup

  1. customplaced in an oil bath
  2. temperatureAfter a total of 5 h at 125° C., the mixture was cooled
  3. extractionextracted with EtOAc (2×100 mL)
  4. washThe combined organic portions were washed twice with 1.0 M aq. H2SO4
  5. dry with materialonce each with half-saturated brine then brine, dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto afford a pale yellow solid

Sources & evidence

ORD record
ord-653ca36f9fbf4cda8bb533e98880ed8d
Source dataset
uspto-grants-2012_09
Patent number
US08263596B2

Reaction notes

Loading…