Tetrahydrofuran → 3-tert-butoxycarbonyl-7-chloro-6-[3-fluoro-4-(3-methylbutyl)-benzylthio]-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 2041388Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2041388
Br[C:2]1[CH:28]=[CH:27][C:5]([CH2:6][S:7][C:8]2[C:18]3[CH2:17][CH2:16][N:15]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:14][CH2:13][C:12]=3[CH:11]=[CH:10][C:9]=2[Cl:26])=[CH:4][C:3]=1[F:29].[Br-].[CH3:31][CH:32]([CH3:36])[CH2:33][CH2:34][Zn+].C1COCC1>C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[C:22]([O:21][C:19]([N:15]1[CH2:16][CH2:17][C:18]2[C:8]([S:7][CH2:6][C:5]3[CH:27]=[CH:28][C:2]([CH2:34][CH2:33][CH:32]([CH3:36])[CH3:31])=[C:3]([F:29])[CH:4]=3)=[C:9]([Cl:26])[CH:10]=[CH:11][C:12]=2[CH2:13][CH2:14]1)=[O:20])([CH3:25])([CH3:24])[CH3:23]

Komponenten

5

Edukt 3

HCID 8028TetrahydrofuranHCID 576562686-(4-bromo-3-fluorobenzylthio)-3-tert-butoxycarbonyl-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepineHCID 178445882HCID 178445882, Verbindung

Produkt 1

HCID 667065573-tert-butoxycarbonyl-7-chloro-6-[3-fluoro-4-(3-methylbutyl)-benzylthio]-2,3,4,5-tetrahydro-1H-benzo[d]azepineAusbeute 42 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 53485975CID 53485975Katalysator

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To 6-(4-bromo-3-fluorobenzylthio)-3-tert-butoxycarbonyl-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.210 mg, 0.42 mmol) and dichloro[1,1′-bis(diphenylphosphino)-ferrocene]palladium(II) dichloromethane adduct (17 mg, 0.021 mmol) add 0.5 M 3-methylbutylzinc bromide in THF (4.2 mL, 2.10 mmol). Degas, purge with dry nitrogen, and stir overnight at 80° C. Cool to ambient temperature, dilute with EtOAc, wash with water, dry over anhydrous MgSO4 and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (9:1) to give 3-tert-butoxycarbonyl-7-chloro-6-[3-fluoro-4-(3-methylbutyl)-benzylthio]-2,3,4,5-tetrahydro-1H-benzo[d]azepine as a yellow oil (85 mg, 42%). Use a method similar to the General Procedure 1-4 to give the title compound as a white solid. MS (ES+) m/z: 392 (M+H)+.

Aufarbeitung

  1. customDegas
  2. custompurge with dry nitrogen
  3. temperatureCool to ambient temperature
  4. additiondilute with EtOAc
  5. washwash with water
  6. dry with materialdry over anhydrous MgSO4
  7. concentrationconcentrate in vacuo
  8. customPurify by chromatography on silica gel eluting with hexane/EtOAc (9:1)

Quellen und Nachweise

ORD-Eintrag
ord-41def21ae59444a4bd3b7f8d7fcd7bd5
Quelldatensatz
uspto-grants-2013_11
Patentnummer
US08580780B2

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