Sodium Hydroxide → (+)-5,6-dimethoxy-2-[2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-yl]-1H-isoindole-1,3(2H)-dione

HRID 2211729

반응식

HRID 2211729 반응식
[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.[CH3:23][O:24][C:25]1[CH:26]=[C:27]2[C:32](=O)[O:31][C:29](=[O:30])[C:28]2=[CH:34][C:35]=1[O:36][CH3:37].C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.[OH-].[Na+]>O1CCCC1.O>[CH3:37][O:36][C:35]1[CH:34]=[C:28]2[C:27](=[CH:26][C:25]=1[O:24][CH3:23])[C:32](=[O:31])[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])[C:29]2=[O:30]

참가 물질

8

반응물 5

HCID 14798Sodium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 6103565,6-Dimethoxy-1,3-dihydro-2-benzofuran-1,3-dioneHCID 106853092,2,4,6,7-Pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-amine

생성물 1

HCID 21961367(+)-5,6-dimethoxy-2-[2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-yl]-1H-isoindole-1,3(2H)-dione수율 85.2%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of (+)-2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-amine (6.00 g, 20.3 mmol) in tetrahydrofuran (50 ml) was added under an argon atmosphere 4,5-dimethoxyphthalic anhydride (4.43 g, 21.3 mmol) and the mixture was refluxed with heating for 3 hours. The reaction mixture was cooled down to room temperature and then 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (WSC) hydrochloride (4.67 g, 24.4 mmol) and 1-hydroxy-1H-benzotriazole (HOBT) monohydrate (3.74 g, 24.4 mmol) were added to the mixture. The resulting mixture was refluxed with heating for 14 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 to obtain 8.40 g of (+)-5,6-dimethoxy-2-[2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-yl]-1H-isoindole-1,3(2H)-dione as a crude product. To a solution of aluminum chloride (13.6 g, 102 mmol) in tetrahydrofuran (60 ml) was added lithium aluminum hydride (3.87 g, 102 mmol) and the resulting mixture was stirred for 10 minutes. To this mixture was added a solution of the above-described crude product in tetrahydrofuran (30 ml) and the resulting mixture was refluxed with heating for 3 hours. The reaction mixture was cooled down to room temperature and water was added into the mixture. The product was extracted twice with ethyl acetate. The combined extracts were washed with a 1 N aqueous solution of sodium hydroxide, dried on magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography (hexane-ethyl acetate 8:1) on silica gel to obtain 6.23 g (68% yield) of the title compound. Melting point: 157-159° C. [α]D=+62.3° (c=0.488, methanol).

후처리

  1. temperaturethe mixture was refluxed
  2. temperaturewith heating for 3 hours
  3. temperatureThe resulting mixture was refluxed
  4. temperaturewith heating for 14 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

출처 및 근거

ORD 기록
ord-3e227019a9ba4ead8223dbf3822c008f
출처 데이터셋
uspto-grants-2006_09
특허 번호
US07101867B2

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