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

HRID 2088165Notes

Reaction equation

HRID 2088165 reaction equation
[N+](=[C:3]([C:8]1[CH:13]=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:11]=[C:10]([C:18]([F:21])([F:20])[F:19])[CH:9]=1)[C:4]([O:6][CH3:7])=[O:5])=[N-].[CH2:22]([N:29]1[C@@H:34]2[CH2:35][CH2:36][C@@:30]1([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[C@H:31]([OH:37])[CH2:32][CH2:33]2)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>C1C=CC=CC=1.C([O-])(=O)C.[Rh+3].C([O-])(=O)C.C([O-])(=O)C>[CH2:22]([N:29]1[C@@H:34]2[CH2:35][CH2:36][C@@:30]1([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[C@H:31]([O:37][C@H:3]([C:4]([O:6][CH3:7])=[O:5])[C:8]1[CH:13]=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:11]=[C:10]([C:18]([F:21])([F:20])[F:19])[CH:9]=1)[CH2:32][CH2:33]2)[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

Participants

5

Reactant 2

HCID 54200568Methyl 2-(3,5-bis(trifluoromethyl)phenyl)-2-diazoacetateHCID 69688994(1R*,2R*,5R*)-8-Benzyl-1-phenyl-8-azabicyclo[3.2.1]octan-2-ol

Product 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

Reagents, catalysts & solvents 2

HCID 168478Rhodium acetateCatalystHCID 241BenzeneSolvent2×

Procedure

Slow addition of methyl 2-diazo-2-(3,5-bis(trifluoromethyl)phenyl)acetate (504 mg, 1.61 mmol) as a solution in benzene (3 ml) to (1R*,2R*,5R*)-8-benzyl-1-phenyl-8-azabicyclo[3.2.1]octan-2-ol (Description 9; 430 mg, 1.47 mmol) in benzene (3 ml) was carried out in the presence of catalytic rhodium acetate (5 mg) at reflux under N2. The reaction mixture was concentrated in vacuo to give a green oil then purified by flash column chromatography [15% ethyl acetate in iso-hexane] to give the title compound as a yellow oil (mainly 1 isomer)(735 mg, 87%).

Workup

  1. temperatureat reflux under N2
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customto give a green oil
  4. customthen purified by flash column chromatography [15% ethyl acetate in iso-hexane]

Sources & evidence

ORD record
ord-75968bcb1d1949dcb7cde7fe288eb8f2
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

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