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

HRID 2088176Notes

Reaction equation

HRID 2088176 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.C(N(CC)CC)C.Cl.CN(C)CCCN=C=NCC.[NH2:67][NH2:68]>C(OCC)(=O)C.ClCCl>[CH2:8]([N:15]1[C@@H:20]2[C@H:21]([C:23]([NH:67][NH2:68])=[O:25])[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:29]=[C:30]([C:38]([F:40])([F:39])[F:41])[CH:31]=[C:32]([C:34]([F:37])([F:35])[F:36])[CH:33]=1)[CH2:18][CH2:19]2)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 9321HydrazineHCID 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 86586714(1R*,2R,5S*,6R*)-8-Benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-1-phenyl-8-azabicyclo[3.2.1]octan-6-carbohydrazideYield 74%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture 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; 1.6 g, 2.35 mmol), triethylamine (1 ml, 7.1 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (910 mg, 4.7 mmol), 4-N,N-dimethylaminopyridine (20 mg, 0.16 mmol), dichloromethane (15 ml) and hydrazine (1M solution in THF, 5 ml, 5 mmol) was stirred at room temperature over the weekend. The reaction mixture was diluted with ethyl acetate and washed with saturated aqueous NaHCO , water and brine. The organic layer was dried (Na2SO4) and concentrated. The residue was purified by chromatography on silica gel (dichloromethane:methanol) to give the title compound (1 g, 74%).

Workup

  1. washwashed with saturated aqueous NaHCO , water and brine
  2. dry with materialThe organic layer was dried (Na2SO4)
  3. concentrationconcentrated
  4. customThe residue was purified by chromatography on silica gel (dichloromethane:methanol)

Sources & evidence

ORD record
ord-10bf3d11771b489a8073c000f9e16bd5
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

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