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

HRID 2088192Notes

Reaction equation

HRID 2088192 reaction equation
C([N:8]1[C@@H:13]2[C@H:14]([C:16]([N:18]3[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]3)=[O:17])[CH2:15][C@@:9]1([C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[C@H:10]([O:24][CH2:25][C:26]1[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[C:28]([C:36]([F:39])([F:38])[F:37])[CH:27]=1)[CH2:11][CH2:12]2)C1C=CC=CC=1>[Pd].C(O)C>[F:39][C:36]([F:37])([F:38])[C:28]1[CH:27]=[C:26]([CH2:25][O:24][C@@H:10]2[CH2:11][CH2:12][C@@H:13]3[NH:8][C@@:9]2([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[CH2:15][C@H:14]3[C:16]([N:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)=[O:17])[CH:31]=[C:30]([C:32]([F:33])([F:35])[F:34])[CH:29]=1

Participants

4

Reactant 1

HCID 86586736(1R*,2R*,5S*,6R*)-8-Benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy)-6-piperidinylcarbonyl-1-phenyl-8-azabicyclo[3.2.1]octane

Product 1

HCID 86586737(1R*,2R*,5S*,6R*)-2-{[3,5-Bis(trifluoromethyl)phenyl]methoxy}-6-piperidinylcarbonyl-1-phenyl-8-azabicyclo[3.2.1]octaneYield 96%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

A mixture of (1R*,2R*,5S*,6R*)-8-benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-6-piperidinylcarbonyl-1-phenyl-8-azabicyclo[3.2.1]octane (Example 120; 100 mg, 0.16 mmol), 10% palladium on charcoal (180 mg) and ethanol (10 ml) was stirred under hydrogen atmosphere (1 atm) at +65° C. for 1 hour. The reaction mixture was cooled to room temperature, flushed with nitrogen gas and filtered through a pad of Celite™. The filtrate was concentrated and purified chromatography on silica gel to give the title compound (83 mg, 90%). The hydrochloride salt of the title compound was prepared by treatment with ethereal HCl.

Workup

  1. customflushed with nitrogen gas
  2. filtrationfiltered through a pad of Celite™
  3. concentrationThe filtrate was concentrated
  4. custompurified chromatography on silica gel

Sources & evidence

ORD record
ord-3fd5b61eda594378b31b1aa0c2df5e5c
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

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