3,4-Dimethylphenol → 1-(diphenylmethyl)-3-hydroxy-3-(2-hydroxy-4,5-dimethylphenyl)-1,3-dihydro-2H-indol-2-one

HRID 1407383Notes

Reaction equation

HRID 1407383 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([OH:9])[CH:5]=[CH:6][C:7]=1[CH3:8].C([Mg]Cl)(C)C.[C:15]1([CH:21]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[N:22]2[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[C:24](=[O:31])[C:23]2=[O:32])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>O1CCCC1>[C:33]1([CH:21]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[N:22]2[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[C:24]([OH:31])([C:5]3[CH:6]=[C:7]([CH3:8])[C:2]([CH3:1])=[CH:3][C:4]=3[OH:9])[C:23]2=[O:32])[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1

Participants

5

Reactant 3

HCID 72493,4-DimethylphenolHCID 19692771-(diphenylmethyl)-1H-indole-2,3-dioneHCID 178418918HCID 178418918, compound

Product 1

HCID 673570991-(diphenylmethyl)-3-hydroxy-3-(2-hydroxy-4,5-dimethylphenyl)-1,3-dihydro-2H-indol-2-oneYield 73.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 3,4-dimethylphenol (2.50 g, 20.5 mmol) in tetrahydrofuran (100 mL) was added isopropylmagnesium chloride (10.2 mL, 2.0 M tetrahydrofuran solution, 20.40 mmol) at 0° C. The mixture was allowed to stir for 1 h at 0° C., then the solvent was removed in vacuo. Dichloromethane (200 mL) was added, followed by the addition of 1-(diphenylmethyl)-1H-indole-2,3-dione (5.00 g, 15.95 mmol). The mixture was stirred for 54 h at ambient temperature, quenched with saturated ammonium chloride solution. The organic layer was washed with water, brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo, the residue was purified by column chromatography to give 1-(diphenylmethyl)-3-hydroxy-3-(2-hydroxy-4,5-dimethylphenyl)-1,3-dihydro-2H-indol-2-one (5.10 g, 73%): 1H NMR (300 MHz, CDCl3) δ7.49-7.45 (m, 1H), 7.35-7.27 (m, 10H), 7.08-7.04 (m, 2H), 6.93 (s, 1H), 6.81-6.75 (m, 1H), 6.52 (s, 1H), 6.49-6.46 (m, 1H), 2.15 (s, 3H), 2.02 (s, 3H); MS (ES+) m/z 418.1 (M−17).

Workup

  1. customthe solvent was removed in vacuo
  2. additionDichloromethane (200 mL) was added
  3. stirringThe mixture was stirred for 54 h at ambient temperature
  4. customquenched with saturated ammonium chloride solution
  5. washThe organic layer was washed with water, brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated in vacuo
  9. customthe residue was purified by column chromatography

Sources & evidence

ORD record
ord-2bc4854096e5465cbcbf615b6595a7e9
Source dataset
uspto-grants-2014_12
Patent number
US08916580B2

Reaction notes

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