Sodium Carbonate → 5,6-Dimethoxy-2-[2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-yl]isoindoline

HRID 1017838Notes

Reaction equation

HRID 1017838 reaction equation
[CH3:1][C:2]1([CH3:22])[CH:6]([C:7]2[CH:12]=[CH:11][C:10]([CH3:13])=[CH:9][CH:8]=2)[C:5]2[C:14]([CH3:21])=[C:15]([NH2:20])[C:16]([CH3:19])=[C:17]([CH3:18])[C:4]=2[O:3]1.Cl[CH2:24][C:25]1[CH:30]=[C:29]([O:31][CH3:32])[C:28]([O:33][CH3:34])=[CH:27][C:26]=1[CH2:35]Cl.C(=O)([O-])[O-].[Na+].[Na+]>O1CCCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH3:34][O:33][C:28]1[CH:27]=[C:26]2[C:25](=[CH:30][C:29]=1[O:31][CH3:32])[CH2:24][N:20]([C:15]1[C:16]([CH3:19])=[C:17]([CH3:18])[C:4]3[O:3][C:2]([CH3:22])([CH3:1])[CH:6]([C:7]4[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][CH:12]=4)[C:5]=3[C:14]=1[CH3:21])[CH2:35]2

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 106853092,2,4,6,7-Pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-amineHCID 109444001,2-Bis(chloromethyl)-4,5-dimethoxybenzene

Product 1

HCID 99119865,6-Dimethoxy-2-[2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-yl]isoindolineYield 16%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-amine (806.1 mg, 2.76 mmol) in tetrahydrofuran (30 ml) were added 1,2-bis(chloromethyl)-4,5-dimethoxybenzene (686.6 mg, 2.92 mmol), sodium carbonate (878.5 g, 8.29 mmol), and tetrabutylammonium iodide (543.6 mg, 1.47 mmol) and the mixture was refluxed with heating for 11 hours. The reaction mixture was cooled down to room temperature and then poured into ice water. The product was extracted twice with ethyl acetate. The combined extracts were washed with an aqueous saturated solution of sodium hydrogen carbonate, dried on magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was crystallized from ethyl acetate-hexane to obtain 199.6 mg (16% yield) of the title compound. Melting point: 156-159° C.

Workup

  1. temperaturethe mixture was refluxed
  2. temperaturewith heating for 11 hours
  3. extractionThe product was extracted twice with ethyl acetate
  4. washThe combined extracts were washed with an aqueous saturated solution of sodium hydrogen carbonate
  5. customdried on magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was crystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-ed8af88d241842788b4886cbfb6c3547
Source dataset
uspto-grants-2002_11
Patent number
US06479536B1

Reaction notes

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