Dimethylformamide → 3-tert-butoxycarbonyl-7-chloro-6-(3-methoxycarbonyl-propyloxy)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 911231Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 911231
Br[CH2:2][CH2:3][CH2:4][C:5]([O:7][CH3:8])=[O:6].[C:9]([O:13][C:14]([N:16]1[CH2:22][CH2:21][C:20]2[C:23]([OH:28])=[C:24]([Cl:27])[CH:25]=[CH:26][C:19]=2[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10].C1CCN2C(=NCCC2)CC1.CN(C=O)C>CCCCCC.CCOC(C)=O>[C:9]([O:13][C:14]([N:16]1[CH2:22][CH2:21][C:20]2[C:23]([O:28][CH2:2][CH2:3][CH2:4][C:5]([O:7][CH3:8])=[O:6])=[C:24]([Cl:27])[CH:25]=[CH:26][C:19]=2[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:10])[CH3:11]

Komponenten

6

Edukt 4

HCID 6228DimethylformamideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 107604Methyl 4-bromobutyrateHCID 574477413-tert-Butoxycarbonyl-7-chloro-6-hydroxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Produkt 1

HCID 667067363-tert-butoxycarbonyl-7-chloro-6-(3-methoxycarbonyl-propyloxy)-2,3,4,5-tetrahydro-1H-benzo[d]azepineAusbeute 76,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 21226206Ethyl acetate hexaneLösungsmittel

Versuchsvorschrift

Add methyl 4-bromobutyrate (1.9 mL, 10.4 mmol) to a mixture of 3-tert-butoxycarbonyl-7-chloro-6-hydroxy-2,3,4,5-tetrahydro-benzo[d]azepine (310 mg, 1.0 mmol), DBU (0.23 mL, 1.6 mmol) and DMF (10 mL) at ambient temperature under nitrogen. Stir the reaction mixture for 16 h. Dilute with hexane/EtOAc (1:1, 60 mL), wash the mixture with 10% aqueous NaCl (4×25 mL), dry the organic layer over Na2SO4 and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (19:1 to 2:3) to obtain 3-tert-butoxycarbonyl-7-chloro-6-(3-methoxycarbonyl-propyloxy)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (303 mg, 73%). MS (ES+) m/z: 398 (+H)+.

Aufarbeitung

  1. washwash the mixture with 10% aqueous NaCl (4×25 mL)
  2. dry with materialdry the organic layer over Na2SO4
  3. concentrationconcentrate in vacuo
  4. customPurify by chromatography on silica gel eluting with hexane/EtOAc (19:1 to 2:3)

Quellen und Nachweise

ORD-Eintrag
ord-5f1b7fcab72b49929961b70e6b4ece60
Quelldatensatz
uspto-grants-2011_09
Patentnummer
US08022062B2

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