Sodium hydride → HCID 66976171, Verbindung

HRID 1022634Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1022634
[H-].[Na+].[C:3]([C:5]1[C:6]([OH:11])=[N:7][CH:8]=[CH:9][CH:10]=1)#[N:4].[Br-].[Li+].[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([C@@H:21]2[O:27][CH2:26][CH2:25][N:24]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:23][C@H:22]2[CH2:35]OS(C)(=O)=O)=[CH:17][C:16]=1[F:41]>COCCOC.CN(C=O)C>[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([C@@H:21]2[O:27][CH2:26][CH2:25][N:24]([C:28]([O:30][C:31]([CH3:33])([CH3:32])[CH3:34])=[O:29])[CH2:23][C@H:22]2[CH2:35][N:7]2[CH:8]=[CH:9][CH:10]=[C:5]([C:3]#[N:4])[C:6]2=[O:11])=[CH:17][C:16]=1[F:41]

Komponenten

7

Edukt 4

HCID 24758Sodium hydrideHCID 82050Lithium BromideHCID 86663855tert-butyl (6S,7R)-7-(4-chloro-3-fluorophenyl)-6-{[(methylsulfonyl)oxy]methyl}-1,4-oxazepane-4-carboxylateHCID 178510022HCID 178510022, Verbindung

Produkt 1

HCID 66976171HCID 66976171, VerbindungAusbeute 83,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 80711,2-DimethoxyethaneLösungsmittel2×

Versuchsvorschrift

60% Sodium hydride (0.274 g, 6.85 mmol) was added to a mixed solution of 3-cyano-2-hydroxypyridine (0.658 g, 5.48 mmol) in 1,2-dimethoxyethane (10 mL)-DMF (5 ml) under ice-cooling, and the mixture was stirred for 20 min. To the reaction solution was added lithium bromide (0.793 g, 9.13 mmol), and the mixture was stirred at room temperature for 1.5 hr. To the reaction solution was added a solution of tert-butyl (6S,7R)-7-(4-chloro-3-fluorophenyl)-6-{[(methylsulfonyl)oxy]methyl}-1,4-oxazepane-4-carboxylate (2 g, 4.57 mmol) in 1,2-dimethoxyethane (10 ml), and the mixture was stirred at 60° C. overnight. The reaction mixture was concentrated under reduced pressure, water was added to the residue, and the mixture was extracted with ethyl acetate. The extract was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography to give the title compound (1.757 g, 3.80 mmol, 83%).

Aufarbeitung

  1. temperaturecooling
  2. stirringthe mixture was stirred at room temperature for 1.5 hr
  3. stirringthe mixture was stirred at 60° C. overnight
  4. concentrationThe reaction mixture was concentrated under reduced pressure, water
  5. additionwas added to the residue
  6. extractionthe mixture was extracted with ethyl acetate
  7. washThe extract was washed with brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. customThe solvent was evaporated under reduced pressure
  10. customThe residue was purified by silica gel column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-ce99abeded494467ab46034888ec7339
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08722662B2

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