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

HRID 2088159Notes

Reaction equation

HRID 2088159 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.C(O)(=O)C>C(OCC)(=O)C.[OH-].[Pd+2].[OH-]>[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

5

Reactant 2

HCID 176Acetic AcidHCID 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 80%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 8857Ethyl AcetateSolvent

Procedure

(1R*,2R*,5R*)-8-Benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-1-phenyl-8-azabicyclo[3.2.1]octane (Example 59; 1.21 g, 2.33 mmol) was dissolved in ethyl acetate (20 ml) then 10% palladium hydroxide(0.13 mg) added. Glacial acetic acid (2 ml) was added and the mixture hydrogenated at room temperature at 40 psi overnight. The reaction mixture was filtered then concentrated in vacuo. The yellow oil was basified (saturated sodium hydrogen carbonate solution), and the solution extracted with dichloromethane (×3), dried (MgSO4) and concentrated in vacuo to give a yellow oil. The reaction mixture was purified by flash column chromatography [5%-15% methanol in dichloromethane] to give the title compound as a yellow oil (0.80 g, 80%).

Workup

  1. customhydrogenated at room temperature
  2. customat 40 psi overnight
  3. filtrationThe reaction mixture was filtered
  4. concentrationthen concentrated in vacuo
  5. extractionthe solution extracted with dichloromethane (×3)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customto give a yellow oil
  9. customThe reaction mixture was purified by flash column chromatography [5%-15% methanol in dichloromethane]

Sources & evidence

ORD record
ord-0e7d8f2c26334f7c99964b197d8c868d
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

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