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

HRID 911225Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 911225
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:16][CH2:15][C:14]2[C:17]([OH:22])=[C:18]([Cl:21])[CH:19]=[CH:20][C:13]=2[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].Br.Br[CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=1>CN(C=O)C>[C:3]([O:7][C:8]([N:10]1[CH2:16][CH2:15][C:14]2[C:17]([O:22][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=3)=[C:18]([Cl:21])[CH:19]=[CH:20][C:13]=2[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 27347202-(Bromomethyl)pyridine hydrobromideHCID 574477413-tert-Butoxycarbonyl-7-chloro-6-hydroxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Produkt 1

HCID 667063923-tert-butoxycarbonyl-7-chloro-6-(pyridin-2-ylmethoxy)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel3×

Reaktionsbedingungen

Temperatur
65 °C

Versuchsvorschrift

Prepare a slurry of sodium hydride (60% in mineral oil, 168 mg, 4.2 mmol) in DMF (4 mL) and heat to 65° C. Add dropwise a solution of 3-tert-butoxycarbonyl-7-chloro-6-hydroxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (250 mg, 0.84 mmol) in DMF (5 mL) and stir for 1 h. Add a solution of 2-(bromomethyl)-pyridine hydrobromide (256 mg, 1 mmol) in DMF (1 mL), stir at 65° C. for 0.5 h and cool to ambient temperature. Add water (1 mL) and concentrate the reaction mixture to an oily residue. Partition the residue between EtOAc/hexane (1:1) and water. Dry the organic layer over Na2SO4, filter and concentrate. Purify by chromatography on silica gel eluting with hexane/EtOAc (10:1, 5:1 and 3:1) to give 3-tert-butoxycarbonyl-7-chloro-6-(pyridin-2-ylmethoxy)-2,3,4,5-tetrahydro-1H-benzo[d]azepine as an oil.

Aufarbeitung

  1. stirringstir at 65° C. for 0.5 h
  2. temperaturecool to ambient temperature
  3. concentrationAdd water (1 mL) and concentrate the reaction mixture to an oily residue
  4. customPartition the residue between EtOAc/hexane (1:1) and water
  5. dry with materialDry the organic layer over Na2SO4
  6. filtrationfilter
  7. concentrationconcentrate
  8. customPurify by chromatography on silica gel eluting with hexane/EtOAc (10:1, 5:1 and 3:1)

Quellen und Nachweise

ORD-Eintrag
ord-17d9880dee094b658019237ab96cbba8
Quelldatensatz
uspto-grants-2011_09
Patentnummer
US08022062B2

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