(3R,11bR)-1,3,4,6,7,11b-Hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-2H-benzo(a)quinolizin-2-one → alpha-Dihydrotetrabenazine

HRID 1665801

Reaktionsgleichung

Reaktionsgleichung von HRID 1665801
[CH3:1][CH:2]([CH2:4][C@H:5]1[C:18](=[O:19])[CH2:17][C@H:16]2[N:7]([CH2:8][CH2:9][C:10]3[C:15]2=[CH:14][C:13]([O:20][CH3:21])=[C:12]([O:22][CH3:23])[CH:11]=3)[CH2:6]1)[CH3:3].[BH4-].[Na+]>CCO>[CH2:4]([C@@H:5]1[CH2:6][N:7]2[CH2:8][CH2:9][C:10]3[C:15]([C@H:16]2[CH2:17][C@H:18]1[OH:19])=[CH:14][C:13]([O:20][CH3:21])=[C:12]([O:22][CH3:23])[CH:11]=3)[CH:2]([CH3:3])[CH3:1].[CH2:4]([C@@H:5]1[CH2:6][N:7]2[CH2:8][CH2:9][C:10]3[C:15]([C@H:16]2[CH2:17][C@@H:18]1[OH:19])=[CH:14][C:13]([O:20][CH3:21])=[C:12]([O:22][CH3:23])[CH:11]=3)[CH:2]([CH3:3])[CH3:1]

Komponenten

5

Edukt 2

HCID 667453(3R,11bR)-1,3,4,6,7,11b-Hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-2H-benzo(a)quinolizin-2-oneHCID 4311764Sodium borohydride

Produkt 2

HCID 14580381alpha-DihydrotetrabenazineHCID 14580382beta-Dihydrotetrabenazine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 702EthanolLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

(3R,11bR)-Tetrabenazine 1c.1 (2 g, 6.3 mmol) was dissolved in EtOH (70 mL) and cooled to 0° C. Sodium borohydride (261 mg, 6.9 mmol) was then added in portions at 0° C. The reaction was complete after 30 minutes and quenched with saturated NH4Cl (4 mL). The white precipitate formed was filtered and washed with EtOH (5 mL, 2×). The EtOH was removed in vacuo and the aqueous layer extracted 3× with CH2Cl2 (50 mL). The organic layers were combined, dried over MgSO4 and concentrated. The crude product was purified via flash column chromatography (0.5:9.5 MeOH:CH2Cl2) to give 1.6 g (5 mmol) of (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol ((2R,3R,11bR)-dihydrotetrabenazine) 1d.1 and 410 mg (1.3 mmol) of (2S,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol ((2S,3R,1bR)-dihydrotetrabenazine) 1d.2. (2R,3R,11bR)-Dihydrotetrabenazine 1d.1: MS calcd: (319); Found 320.3 (M+H). (2S,3R,11bR)-Dihydrotetrabenazine 1d.2: MS calcd: (319); Found 320.3 (M+H).

Aufarbeitung

  1. customquenched with saturated NH4Cl (4 mL)
  2. customThe white precipitate formed
  3. filtrationwas filtered
  4. washwashed with EtOH (5 mL, 2×)
  5. customThe EtOH was removed in vacuo
  6. extractionthe aqueous layer extracted 3× with CH2Cl2 (50 mL)
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customThe crude product was purified via flash column chromatography (0.5:9.5 MeOH:CH2Cl2)

Quellen und Nachweise

ORD-Eintrag
ord-41a2dcecd9044411908028d8e67da474
Quelldatensatz
uspto-grants-2011_10
Patentnummer
US08039627B2

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