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

HRID 2088166Notes

Reaction equation

HRID 2088166 reaction equation
C([N:8]1[C@@H:13]2[CH2:14][CH2:15][C@@:9]1([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[C@H:10]([O:16][C@H:17]([C:32]([O:34][CH3:35])=[O:33])[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(OCC)(=O)C.C(O)(=O)C.[OH-].[Pd+2].[OH-]>[F:31][C:28]([F:29])([F:30])[C:20]1[CH:19]=[C:18]([C@@H:17]([C:32]([O:34][CH3:35])=[O:33])[O:16][C@@H:10]2[CH2:11][CH2:12][C@@H:13]3[NH:8][C@@:9]2([C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)[CH2:15][CH2:14]3)[CH:23]=[C:22]([C:24]([F:25])([F:26])[F:27])[CH:21]=1

Participants

5

Reactant 1

HCID 86586700(1R*,2R*,5R*)-8-Benzyl-2-{(1S*)-1-[3,5-bis(trifluoromethyl)phenyl]-(methoxycarbonyl)methoxy}-1-phenyl-8-azabicyclo[3.2.1]octane

Product 1

HCID 86586701(1R*,2R*,5R*)-2-{(1S*)-1-[3,5-Bis(trifluoromethyl)phenyl]-(methoxycarbonyl)methoxy}-1-phenyl-8-azabicyclo[3.2.1]octane

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Procedure

(1R*,2R*,5R*)-8-Benzyl-2-{(1S*)-1-[3,5-bis(trifluoromethyl)phenyl]-(methoxycarbonyl)methoxy}-1-phenyl-8-azabicyclo[3.2.1]octane (Example 70; 735 mg, 1.27 mmol) was dissolved in ethyl acetate (10 ml) with glacial acetic acid (0.5 ml) and 10% palladium hydroxide (40 mg) added. The mixture was hydrogenated on a Parr™ at 40 psi overnight. The mixture was filtered through Celite™, then concentrated in vacuo and the residue basified with saturated sodium hydrogen carbonate solution. The solution was then extracted with ethyl acetate (×3) and the extracts dried (MgSO4) and concentrated in vacuo. The obtained oil was purified by flash column chromatography [10% methanol in dichloromethane) to give the title compound as a yellow oil. (5:1 desired:undesired). (323 mg, 52%).

Workup

  1. additionadded
  2. customwas hydrogenated on a Parr™ at 40 psi overnight
  3. filtrationThe mixture was filtered through Celite™
  4. concentrationconcentrated in vacuo
  5. extractionThe solution was then extracted with ethyl acetate (×3)
  6. dry with materialthe extracts dried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customThe obtained oil was purified by flash column chromatography [10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-ff8edde390d94fe38b0f721b341cf791
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

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