Ammonia → (1R*,2R*,5S*,6R*)-8-Benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-1-phenyl-8-azabicyclo[3.2.1]octan-6-carboxamide

HRID 2088167Notes

Reaction equation

HRID 2088167 reaction equation
FC(F)(F)C(O)=O.[CH2:8]([N:15]1[C@@H:20]2[C@H:21]([C:23]([OH:25])=O)[CH2:22][C@@:16]1([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[C@H:17]([O:26][CH2:27][C:28]1[CH:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[C:30]([C:38]([F:41])([F:40])[F:39])[CH:29]=1)[CH2:18][CH2:19]2)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.N.O1CCOCC1.C([N:57](CC)CC)C.Cl.CN(C)CCCN=C=NCC>C(OCC)(=O)C>[CH2:8]([N:15]1[C@@H:20]2[C@H:21]([C:23]([NH2:57])=[O:25])[CH2:22][C@@:16]1([C:42]1[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=1)[C@H:17]([O:26][CH2:27][C:28]1[CH:33]=[C:32]([C:34]([F:35])([F:37])[F:36])[CH:31]=[C:30]([C:38]([F:39])([F:41])[F:40])[CH:29]=1)[CH2:18][CH2:19]2)[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

Participants

7

Reactant 5

HCID 222AmmoniaHCID 8471TriethylamineHCID 312751,4-DioxaneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86586685(1R*,2R*,5S*,6R*)-8-Benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-1-phenyl-8-azabicyclo[3.2.1]octan-6-carboxylic acid trifluoroacetate

Product 1

HCID 86586702(1R*,2R*,5S*,6R*)-8-Benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-1-phenyl-8-azabicyclo[3.2.1]octan-6-carboxamideYield 56%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A solution of (1R*,2R*,5S*,6R*)-8-benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-1-phenyl-8-azabicyclo[3.2.1]octan-6-carboxylic acid trifluoroacetate (Example 53; 2.7 mmol) was treated with ammonia solution in dioxane (0.5M, 10 ml, 5 mmol), triethylamine (0.6 ml, 4.3 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (960 mg, 5.02 mmol), and 4-N,N-dimethylaminopyridine (120 mg, 1 mmol). The mixture was stirred for 24 hours, diluted with ethyl acetate (100 ml), washed with 10% aqueous citric acid, saturated aqueous NaHCO3, dried (Na2SO4) and concentrated. The residue was purified by chromatography on silica gel (iso-hexane:ethyl acetate) to give the title compound (850 mg, 56%).

Workup

  1. washwashed with 10% aqueous citric acid, saturated aqueous NaHCO3
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated
  4. customThe residue was purified by chromatography on silica gel (iso-hexane:ethyl acetate)

Sources & evidence

ORD record
ord-5f4871e1935b4186bad224b6d093cc52
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

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