Sodium hydride → (1R*,2R*,5S*,6R*)-8-Benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-6-cyano-1-phenyl-8-azabicyclo[3.2.1]octane

HRID 2088201Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2088201
[H-].[Na+].[F:3][C:4]([F:18])([F:17])[C:5]1[CH:6]=[C:7]([CH:10]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:12]=1)[CH2:8]Br.[CH2:19]([N:26]1[C@@H:31]2[C@H:32]([C:34]#[N:35])[CH2:33][C@@:27]1([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[C@H:28]([OH:36])[CH2:29][CH2:30]2)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C1COCC1>[CH2:19]([N:26]1[C@@H:31]2[C@H:32]([C:34]#[N:35])[CH2:33][C@@:27]1([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[C@H:28]([O:36][CH2:8][C:7]1[CH:6]=[C:5]([C:4]([F:18])([F:17])[F:3])[CH:12]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:10]=1)[CH2:29][CH2:30]2)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 1225733,5-Bis(trifluoromethyl)benzyl bromideHCID 69890225(1R*,2R*,5S*,6R*)-8-Benzyl-6-cyano-1-phenyl-8-azabicyclo[3.2.1]octan-2-ol

Produkt 1

HCID 86586749(1R*,2R*,5S*,6R*)-8-Benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-6-cyano-1-phenyl-8-azabicyclo[3.2.1]octaneAusbeute 88,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

Sodium hydride (0.3 g, 7.5 mmol, 60% in oil) was added portionwise to a solution of 3,5-bis(trifluoromethyl)benzyl bromide (2.5 g, 8.3 mmol) and (1R*,2R*,5S*,6R*)-8-benzyl-6-cyano-1-phenyl-8-azabicyclo[3.2.1]octan-2-ol (Description 31; 1.4 g, 4.4 mmol) in THF (20 ml). The mixture was stirred at 50° C. for 18 hours then cooled with an ice-bath and quenched by dropwise addition of water. The mixture was partitioned between brine and ethyl acetate. The organic layer was separated, dried (MgSO4), filtered and concentrated. Chromatography on silica gel eluting with 2.5, 5, 10 and 20% ethyl acetate/iso-hexanes afforded the title compound (2.12 g, 88%).

Aufarbeitung

  1. temperaturethen cooled with an ice-bath
  2. customquenched by dropwise addition of water
  3. customThe mixture was partitioned between brine and ethyl acetate
  4. customThe organic layer was separated
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-e526b1e1d1814940825cc9135244a450
Quelldatensatz
uspto-grants-2004_04
Patentnummer
US06727249B2

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