Methanol → (1R*,2R*,5S*,6R*)-2-{[3,5-Bis(trifluoromethyl)phenyl]methoxy}-6-(1-methyl-1H-tetrazol-5-yl)-1-phenyl-8-azabicyclo[3.2.1]octane

HRID 2088215Notes

Reaction equation

HRID 2088215 reaction equation
C([N:8]1[C@@H:13]2[C@H:14]([C:16]3[N:17]=[N:18][N:19](C)[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.[CH3:44]O>[Pd]>[NH3:8].[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[N:20]([CH3:44])[N:19]=[N:18][N:17]=2)[CH:29]=[C:28]([C:30]([F:31])([F:32])[F:33])[CH:27]=1

Participants

5

Reactant 2

HCID 887MethanolHCID 86586751(1R*,2R*,5S*,6R*)-8-benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-6-(2-methyl-2H-tetrazol-5-yl)-1-phenyl-8-azabicyclo[3.2.1]octane

Product 2

HCID 222AmmoniaHCID 86586765(1R*,2R*,5S*,6R*)-2-{[3,5-Bis(trifluoromethyl)phenyl]methoxy}-6-(1-methyl-1H-tetrazol-5-yl)-1-phenyl-8-azabicyclo[3.2.1]octaneYield 58%

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

Palladium on carbon (10%) 100 mg was added to a solution of (1R*,2R*,5S*,6R*)-8-benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-6-(1-methyl-1H-tetrazol-5-yl)-1-phenyl-8-azabicyclo[3.2.1]octane (Example 139a; 170 mg, 0.3 mmol) in methanol (10 ml). The mixture was transferred to the Parr™ apparatus and hydrogenated at 45 psi. for 2 hours. The mixture was filtered through Celite™ and the filtrate concentrated in vacuo. The residue was chromatographed on silica gel eluting with 180:8:1 dichloromethane:methanol:ammonia to yield the title compound (84 mg, 58%). The hydrochloride salt was prepared by treatment with ethereal HCl.

Workup

  1. filtrationThe mixture was filtered through Celite™
  2. concentrationthe filtrate concentrated in vacuo
  3. customThe residue was chromatographed on silica gel eluting with 180:8:1 dichloromethane

Sources & evidence

ORD record
ord-fa82a6e1bf944ba79d99f84add110b2f
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

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