Ammonium → (r)-(+)-5,6-Dimethoxy-2-(2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-yl)isoindoline

HRID 1815665

Reaktionsgleichung

Reaktionsgleichung von HRID 1815665
Cl.[CH3:2][O:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[CH2:9][N:8]([C:15]1[C:16]([CH3:35])=[C:17]([CH3:34])[C:18]3[O:22][C:21]([CH3:24])([CH3:23])[C@H:20]([C:25]4[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=4)[C:19]=3[C:32]=1[CH3:33])[CH2:7]2.C(C1C=C(O)C=C(C(C)(C)C)C=1C)(C)(C)C.[NH4+].O>C(O)C.Cl>[CH3:2][O:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[CH2:9][N:8]([C:15]1[C:16]([CH3:35])=[C:17]([CH3:34])[C:18]3[O:22][C:21]([CH3:24])([CH3:23])[C@H:20]([C:25]4[CH:26]=[CH:27][C:28]([CH3:31])=[CH:29][CH:30]=4)[C:19]=3[C:32]=1[CH3:33])[CH2:7]2

Komponenten

7

Edukt 4

HCID 223AmmoniumHCID 962WaterHCID 102200963,5-Di-tert-butyl-4-methylphenolHCID 68438410(r)-(+)-5,6-Dimethoxy-2-(2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-yl) isoindoline hydrochloride

Produkt 1

HCID 9846933(r)-(+)-5,6-Dimethoxy-2-(2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-yl)isoindolineAusbeute 75,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 313Hydrochloric AcidLösungsmittelHCID 702EthanolLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

To a solution of 1,2-bischloromethylveratrol (675.9 g) in toluene (4000 ml) was added dropwise a solution of (+)-2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-amine (800 g) and N-ethyldiisopropylamine (943.2 g) in toluene (3867 ml) under nitrogen stream, with heating at the inner temperature of 100° C. for 4.5 hr. After dropping, the mixture was further stirred at 100° C. for 1 hr. The mixture was cooled to the inner temperature of 45° C., methanol (1040 ml) was added thereto and concentrated hydrochloric acid (333.6 ml) was added dropwise thereto. After the crystals were precipitated, the mixture was stirred at 50° C. for 30 min and stirred at 5° C. for 1 hr. The crystals were collected by filtration, and washed with toluene and 50% ethanol to give (R)-(+)-5,6-dimethoxy-2-(2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-yl) isoindoline hydrochloride (1119 g, 83.6%). This hydrochloride was dissolved in a mixed solution of 90% ethanol (5600 ml) and concentrated hydrochloric acid (110 ml), and 2,6-di-tert-butyl-4-hydroxytoluene (8.0 g) was added thereto. To the solution was added dropwise 6.25% aqueous ammonium at 50° C. to adjust the pH to 8.0, and water (640 ml) was added thereto. The mixture was stirred at 50° C. for 30 min and stirred at room temperature for 1 hr. The precipitated crystals were collected by filtration, washed with 70% ethanol to give the title compound (935 g, yield 75.5%).

Aufarbeitung

  1. additionwas added
  2. additionwas added
  3. stirringstirred at room temperature for 1 hr
  4. filtrationThe precipitated crystals were collected by filtration
  5. washwashed with 70% ethanol

Quellen und Nachweise

ORD-Eintrag
ord-33fcebd9b64c4978868dc8e50d02b274
Quelldatensatz
uspto-grants-2005_04
Patentnummer
US06878831B2

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