3-tert-butoxycarbonyl-6-(5-bromopyridin-2-ylmethylthio)-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine → 3-tert-butoxycarbonyl-7-chloro-6-[5-(3-methyl-butyl)-pyridin-2-ylmethylthio]-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 911491Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 911491
Br[C:2]1[CH:3]=[CH:4][C:5]([CH2:8][S:9][C:10]2[C:20]3[CH2:19][CH2:18][N:17]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:16][CH2:15][C:14]=3[CH:13]=[CH:12][C:11]=2[Cl:28])=[N:6][CH:7]=1.[Br-].[CH3:30][CH:31]([CH3:35])[CH2:32][CH2:33][Zn+]>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:24]([O:23][C:21]([N:17]1[CH2:18][CH2:19][C:20]2[C:10]([S:9][CH2:8][C:5]3[CH:4]=[CH:3][C:2]([CH2:33][CH2:32][CH:31]([CH3:35])[CH3:30])=[CH:7][N:6]=3)=[C:11]([Cl:28])[CH:12]=[CH:13][C:14]=2[CH2:15][CH2:16]1)=[O:22])([CH3:27])([CH3:26])[CH3:25]

Komponenten

4

Edukt 2

HCID 576562493-tert-butoxycarbonyl-6-(5-bromopyridin-2-ylmethylthio)-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepineHCID 178445882HCID 178445882, Verbindung

Produkt 1

HCID 667073303-tert-butoxycarbonyl-7-chloro-6-[5-(3-methyl-butyl)-pyridin-2-ylmethylthio]-2,3,4,5-tetrahydro-1H-benzo[d]azepineAusbeute 75 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 53485975CID 53485975Katalysator

Versuchsvorschrift

To 6-(5-bromo-pyridin-2-ylmethylthio)-3-tert-butoxycarbonyl-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine (219 mg, 0.452 mmol) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (18 mg, 0.022 mmol) under dry nitrogen add with stirring a solution of 0.5M 3-methylbutylzinc bromide in TIE (4.6 mL, 2.3 mmol). Degas, purge with dry nitrogen, and stir overnight at 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 (5:1) to give 3-tert-butoxycarbonyl-7-chloro-6-[5-(3-methyl-butyl)-pyridin-2-ylmethylthio]-2,3,4,5-tetrahydro-1H-benzo[d]azepine as an oil (160 mg, 75%). MS (APCI+) m/z: 475 (M+H)+. Use a method similar to the General Procedure 1-4 to give the title compound as a tan solid. MS (APCI+) m/z: 375 (M+M)+.

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag
ord-8f86cdf1989d44bf9aac824bbf5cd2ae
Quelldatensatz
uspto-grants-2011_09
Patentnummer
US08022062B2

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