Sodium hydride → 3-tert-butoxycarbonyl-7-chloro-6-(thiophen-2-ylthiomethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 1670547Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1670547
[H-].[Na+].[S:3]1[CH:7]=[CH:6][CH:5]=[C:4]1[SH:8].[C:9]([O:13][C:14]([N:16]1[CH2:22][CH2:21][C:20]2[C:23]([CH2:28]Cl)=[C:24]([Cl:27])[CH:25]=[CH:26][C:19]=2[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10]>CN(C=O)C.[I-].[K+]>[C:9]([O:13][C:14]([N:16]1[CH2:22][CH2:21][C:20]2[C:23]([CH2:28][S:8][C:4]3[S:3][CH:7]=[CH:6][CH:5]=3)=[C:24]([Cl:27])[CH:25]=[CH:26][C:19]=2[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10]

Komponenten

6

Edukt 3

HCID 24758Sodium hydrideHCID 5226742-ThiophenethiolHCID 597874103-tert-Butoxycarbonyl-7-chloro-6-chloromethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Produkt 1

HCID 673359353-tert-butoxycarbonyl-7-chloro-6-(thiophen-2-ylthiomethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepineAusbeute 70,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 4875Potassium IodideKatalysatorHCID 6228DimethylformamideLösungsmittel2×

Reaktionsbedingungen

Temperatur
45 °C

Versuchsvorschrift

Suspend sodium hydride (20 mg, 60% dispersion in mineral oil) in anhydrous DMF (2 mL) and add thiophene-2-thiol (35 mg, 0.38 mmol) at room temperature. After 5 min add 3-tert-butoxycarbonyl-7-chloro-6-chloromethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine (150 mg, 0.38 mmol) and catalytic potassium iodide (1 mg) in anhydrous DMF (1 mL) and stir at 45° C. for 13 h. Cool the mixture to room temperature and partition between brine and EtOAc. Dry the organic layer over Na2SO4, filter and concentrate in vacuo. Purify the crude mixture by chromatography on silica gel eluting with hexane/EtOAc (1:0 to 7:3 gradient) to give 3-tert-butoxycarbonyl-7-chloro-6-(thiophen-2-ylthiomethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (110 mg).

Aufarbeitung

  1. temperatureCool the mixture to room temperature
  2. custompartition between brine and EtOAc
  3. dry with materialDry the organic layer over Na2SO4
  4. filtrationfilter
  5. concentrationconcentrate in vacuo
  6. customPurify the crude mixture by chromatography on silica gel eluting with hexane/EtOAc (1:0 to 7:3 gradient)

Quellen und Nachweise

ORD-Eintrag
ord-e06239ab55a142d59a6d140e0a7ec016
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US07994163B2

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