(1R*,2R*,5S*,6R*)-8-Benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-6-[4-methyloxazol-2-yl]-1-phenyl-8-azabicyclo[3.2.1]octane → (1R*,2R*,5S*,6R*)-2-{[3,5-Bis(trifluoromethyl)phenyl]methoxy}-6-[4-methyloxazol-2-yl]-1-phenyl-8-azabicyclo[3.2.1]octane

HRID 2088169Notes

Reaction equation

HRID 2088169 reaction equation
C([N:8]1[C@@H:13]2[C@H:14]([C:16]3[O:17][CH:18]=[C:19]([CH3:21])[N:20]=3)[CH2:15][C@@:9]1([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[C@H:10]([O:22][CH2:23][C:24]1[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[C:26]([C:34]([F:37])([F:36])[F:35])[CH:25]=1)[CH2:11][CH2:12]2)C1C=CC=CC=1>[Pd]>[F:37][C:34]([F:35])([F:36])[C:26]1[CH:25]=[C:24]([CH2:23][O:22][C@@H:10]2[CH2:11][CH2:12][C@@H:13]3[NH:8][C@@:9]2([C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH2:15][C@H:14]3[C:16]2[O:17][CH:18]=[C:19]([CH3:21])[N:20]=2)[CH:29]=[C:28]([C:30]([F:33])([F:31])[F:32])[CH:27]=1

Participants

3

Reactant 1

HCID 86586703(1R*,2R*,5S*,6R*)-8-Benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-6-[4-methyloxazol-2-yl]-1-phenyl-8-azabicyclo[3.2.1]octane

Product 1

HCID 86586704(1R*,2R*,5S*,6R*)-2-{[3,5-Bis(trifluoromethyl)phenyl]methoxy}-6-[4-methyloxazol-2-yl]-1-phenyl-8-azabicyclo[3.2.1]octaneYield 84%

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

A mixture of (1R*,12R*,5S*,6R*)-8-benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-6-[4-methyloxazol-2-yl]-1-phenyl-8-azabicyclo[3.2.1]octane (Example 76; 53 mg, 0.09 mmol), 10% palladium on charcoal (135 mg) ethanol (10 ml) was stirred under hydrogen atmosphere (1 atm) at +65° C. for 30 minutes. 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 by preparative TLC (dichloromethane:methanol) to give the title compound (38 mg, 84%). 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 by preparative TLC (dichloromethane:methanol)

Sources & evidence

ORD record
ord-d6c9581b58b6414ca6fb57c6173a2344
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

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