Hydrazine hydrate (1:1) → 1,3-Dihydro-5-methoxy-1-(phenylmethyl)-2H-indol-2-one

HRID 447352Notes

Reaction equation

HRID 447352 reaction equation
[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([O:17][CH3:18])=[CH:14][CH:15]=2)[C:10](=O)[C:9]1=[O:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.NN>CS(C)=O.O.CCOC(C)=O>[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([O:17][CH3:18])=[CH:14][CH:15]=2)[CH2:10][C:9]1=[O:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 11357627N-Benzyl-5-methoxyisatin

Product 1

HCID 113572261,3-Dihydro-5-methoxy-1-(phenylmethyl)-2H-indol-2-oneYield 85.8%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 1-benzyl-5-methoxyindoline-2,3-dione (6.1 g, 23 mmol) and hydrazine hydrate (50-60% grade, 2.9 mL, ca. 2 eq) in DMSO (15 mL) is heated to 140° C. in an oil bath. After 3 h, the mixture was cooled, diluted with water and EtOAc, the layers separated and the aqueous extracted with EtOAc three times (30 mL). The combined organic portions were washed with 2M H2SO4, brine, and dried over MgSO4, filtered and concentrated to afford the crude product as a viscous brown oil. The crude product was purified by silica gel chromatography (20-50% EtOAc in hexane) to yield the title compound as a brown oil (5.0 g, 85%). 1H NMR (400 MHz, CDCl3) δ 7.34-7.23 (m, 5H), 6.89 (s, 1H), 6.69 (d, J=8.3 Hz, 1H), 6.61 (d, J=8.5 Hz, 1H), 4.91 (s, 2H), 3.76 (s, 3H), 3.62 (s, 2H). MS ESI 254.0 [M+H]+, calcd for [C16H1sNO2+H]+ 254.1.

Workup

  1. temperaturethe mixture was cooled
  2. customthe layers separated
  3. extractionthe aqueous extracted with EtOAc three times (30 mL)
  4. washThe combined organic portions were washed with 2M H2SO4, brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto afford the crude product as a viscous brown oil
  9. customThe crude product was purified by silica gel chromatography (20-50% EtOAc in hexane)

Sources & evidence

ORD record
ord-077e2fe138f048c6b49a45ec57f07c34
Source dataset
uspto-grants-2013_07
Patent number
US08481533B2

Reaction notes

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