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

HRID 2088229Notes

Reaction equation

HRID 2088229 reaction equation
C([N:8]1[C@@H:13]2[CH2:14][CH2:15][C@@:9]1([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[C@H:10]([O:16][CH2:17][C:18]1[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[C:20]([C:28]([F:31])([F:30])[F:29])[CH:19]=1)[CH2:11][CH2:12]2)C1C=CC=CC=1>[Pd].C(O)C>[F:26][C:24]([F:25])([F:27])[C:22]1[CH:23]=[C:18]([CH2:17][O:16][C@@H:10]2[CH2:11][CH2:12][C@@H:13]3[NH:8][C@@:9]2([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH2:15][CH2:14]3)[CH:19]=[C:20]([C:28]([F:31])([F:29])[F:30])[CH:21]=1

Participants

4

Reactant 1

HCID 86586691(1R*,2R*,5R*)-8-Benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-1-phenyl-8-azabicyclo[3.2.1]octane

Product 1

HCID 86586647(1R*,2R*,5R*)-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-1-phenyl-8-azabicyclo[3.2.1]octaneYield 59%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

A mixture of (1R,2R,5R)-8-benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-1-phenyl-8-azabicyclo[3.2.1]octane (Example 180; 165 mg), 10% palladium on charcoal (215 mg) and ethanol (15 ml) was stirred under hydrogen atmosphere (1 atm) at +65° C. for 45 minutes. The reaction mixture was cooled to room temperature, flushed with nitrogen gas and filtered through a pad of Celite™. The filtrate was concentrated. The residue was purified by chromatography on silica gel (dichloromethane:methanol:ammonia) to give the title compound (64 mg, 59%). 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. customThe residue was purified by chromatography on silica gel (dichloromethane:methanol:ammonia)

Sources & evidence

ORD record
ord-861a54b193b949a8a62446558a8a9268
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

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