Sodium Hydroxide → 5,6-Dichloro-(2,2,4,6,7-pentamethyl-3-phenyl-2,3-dihydro-1-benzofuran-5-yl)-1H-isoindole-1,3(2H)-dione

HRID 1017828Notes

Reaction equation

HRID 1017828 reaction equation
[CH3:1][C:2]1([CH3:21])[CH:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:5]2[C:13]([CH3:20])=[C:14]([NH2:19])[C:15]([CH3:18])=[C:16]([CH3:17])[C:4]=2[O:3]1.[Cl:22][C:23]1[CH:24]=[C:25]2[C:30](=O)[O:29][C:27](=[O:28])[C:26]2=[CH:32][C:33]=1[Cl:34].C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.[OH-].[Na+]>O1CCCC1.O>[Cl:22][C:23]1[CH:24]=[C:25]2[C:26](=[CH:32][C:33]=1[Cl:34])[C:27](=[O:28])[N:19]([C:14]1[C:15]([CH3:18])=[C:16]([CH3:17])[C:4]3[O:3][C:2]([CH3:21])([CH3:1])[CH:6]([C:7]4[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=4)[C:5]=3[C:13]=1[CH3:20])[C:30]2=[O:29]

Participants

8

Reactant 5

HCID 14798Sodium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 703344,5-Dichlorophthalic anhydrideHCID 757711-HydroxybenzotriazoleHCID 105407985-Amino-2,2,4,6,7-pentamethyl-3-phenyl-2,3-dihydrobenzofuran

Product 1

HCID 219613375,6-Dichloro-(2,2,4,6,7-pentamethyl-3-phenyl-2,3-dihydro-1-benzofuran-5-yl)-1H-isoindole-1,3(2H)-dioneYield 68%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2,2,4,6,7-pentamethyl-3-phenyl-2,3-dihydro-1-benzofuran-5-amine (1.00 g, 3.56 mmol) in tetrahydrofuran (30 ml) was added under an argon atmosphere 4,5-dichlorophthalic anhydride (850.6 mg, 3.92 mmol) and the mixture was refluxed with heating for 13 hours. The reaction mixture was cooled down to room temperature and then 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (WSC) hydrochloride (760.0 mg, 3.96 mmol) and 1-hydroxy-1H-benzotriazole (HOBT) monohydrate (602.6 mg, 3.93 mmol) were added to the mixture. The resulting mixture was refluxed with heating for 3 hours and then cooled down to room temperature. Water and an 8 N aqueous solution of sodium hydroxide were added into the reaction mixture and 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 to obtain 1.16 g (68% yield) of the title compound. Melting point: 178-181° C.

Workup

  1. temperaturethe mixture was refluxed
  2. temperaturewith heating for 13 hours
  3. temperatureThe resulting mixture was refluxed
  4. temperaturewith heating for 3 hours
  5. temperaturecooled down to room temperature
  6. extractionthe product was extracted twice with ethyl acetate
  7. washThe combined extracts were washed with an aqueous, saturated solution of sodium hydrogen carbonate
  8. customdried on magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was crystallized from ethyl acetate

Sources & evidence

ORD record
ord-a9681bec05f74c3e8f431c9c2bd0d697
Source dataset
uspto-grants-2002_11
Patent number
US06479536B1

Reaction notes

Loading…