Tetrahydrofuran → (1R*,2R*,5R*)-8-Benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-1-(4-fluorophenyl)-8-azabicyclo[3.2.1]octane

HRID 2088136Notes

Reaction equation

HRID 2088136 reaction equation
[H-].[Na+].C1COCC1.[CH2:8]([N:15]1[C@@H:20]2[CH2:21][CH2:22][C@@:16]1([C:24]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=1)[C@H:17]([OH:23])[CH2:18][CH2:19]2)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[F:31][C:32]([F:46])([F:45])[C:33]1[CH:34]=[C:35]([CH:38]=[C:39]([C:41]([F:44])([F:43])[F:42])[CH:40]=1)[CH2:36]Br>CCCC(C)C.O>[CH2:8]([N:15]1[C@@H:20]2[CH2:21][CH2:22][C@@:16]1([C:24]1[CH:25]=[CH:26][C:27]([F:30])=[CH:28][CH:29]=1)[C@H:17]([O:23][CH2:36][C:35]1[CH:38]=[C:39]([C:41]([F:43])([F:44])[F:42])[CH:40]=[C:33]([C:32]([F:31])([F:45])[F:46])[CH:34]=1)[CH2:18][CH2:19]2)[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 1225733,5-Bis(trifluoromethyl)benzyl bromideHCID 69889560(1R*,2R*,5R*)-8-Benzyl-1-(4-fluorophenyl)-8-azabicyclo[3.2.1]octan-2-ol

Product 1

HCID 86586658(1R*,2R*,5R*)-8-Benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-1-(4-fluorophenyl)-8-azabicyclo[3.2.1]octaneYield 58%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 78922-MethylpentaneSolvent

Procedure

Sodium hydride (320 mg, 60% in oil, 7.98 mmol) was washed with iso-hexane (×3) then THF (8 ml) and (1R*,2R*,5R*)-8-benzyl-1-(4-fluorophenyl)-8-azabicyclo[3.2.1]octan-2-ol (Description 15; 1.24 g, 3.99 mmol) added and the mixture stirred at room temperature for 10 minutes then 3,5-bis(trifluoromethyl) benzyl bromide added and the reaction mixture stirred at 60° C. overnight. The reaction mixture was poured into water and extracted with ethyl acetate (×3), dried (MgSO4) and concentrated in vacuo to give a yellow oil. This was purified by flash column chromatography [5% ethyl acetate in iso-hexane] to give the title compound (1.51 g, 58%).

Workup

  1. stirringthe reaction mixture stirred at 60° C. overnight
  2. extractionextracted with ethyl acetate (×3)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customto give a yellow oil
  6. customThis was purified by flash column chromatography [5% ethyl acetate in iso-hexane]

Sources & evidence

ORD record
ord-83a9fe0363344d30b572e19b1a34e0f2
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

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