Methyl iodide → (1R*,2R*,5S*,6R*)-8-benzyl-2-{(1R*)-1-[3,5-bis(trifluoromethyl)phenyl]-2-phenylmethoxyethoxy}-6-(1-methyl-1H-tetrazol-5-yl)-1-phenyl-8-azabicyclo[3.2.1]octane

HRID 2088220Notes

Reaction equation

HRID 2088220 reaction equation
[CH2:1]([N:8]1[C@@H:13]2[C@H:14]([C:16]3[NH:20][N:19]=[N:18][N:17]=3)[CH2:15][C@@:9]1([C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)[C@H:10]([O:21][C@H:22]([C:32]1[CH:37]=[C:36]([C:38]([F:41])([F:40])[F:39])[CH:35]=[C:34]([C:42]([F:45])([F:44])[F:43])[CH:33]=1)[CH2:23][O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[CH2:11][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CI.[C:54](=O)([O-])[O-].[K+].[K+]>C(#N)C>[CH2:1]([N:8]1[C@@H:13]2[C@H:14]([C:16]3[N:17]([CH3:54])[N:18]=[N:19][N:20]=3)[CH2:15][C@@:9]1([C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)[C@H:10]([O:21][C@H:22]([C:32]1[CH:37]=[C:36]([C:38]([F:39])([F:40])[F:41])[CH:35]=[C:34]([C:42]([F:44])([F:45])[F:43])[CH:33]=1)[CH2:23][O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[CH2:11][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 178506189(1R*,2R*,5S*,6R*)-8-Benzyl-2-{(1R*)-1-[3,5-bis(trifluoromethyl)phenyl]-2-phenylmethoxyethoxy}-1-phenyl-6-(tetrazol-5-yl)-8-azabicyclo[3.2.1]octane

Product 1

HCID 86586770(1R*,2R*,5S*,6R*)-8-benzyl-2-{(1R*)-1-[3,5-bis(trifluoromethyl)phenyl]-2-phenylmethoxyethoxy}-6-(1-methyl-1H-tetrazol-5-yl)-1-phenyl-8-azabicyclo[3.2.1]octane

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

(1R*,2R*,5S*,6R*)-8-Benzyl-2-{(1R*)-1-[3,5-bis(trifluoromethyl)phenyl]-2-phenylmethoxyethoxy}1-phenyl-6-(tetrazol-5-yl)-8-azabicyclo[3.2.1]octane (Example 158; 0.403 g, 0.57 mmol), methyl iodide (0.2427 g, 0.107 ml, 1.71 mmol) and potassium carbonate (0.236 g, 1.71 mmol) in acetonitrile (10 ml) were heated at 60° C. for 2 hours. The mixture was quenched with water and concentrated in vacuo. The residue was partitioned between ethyl acetate and water. The organics were collected, dried (MgSO4) and concentrated in vacuo. The residue was purified by flash column chromatography, eluting with 1% methanol/dichloromethane to give the title compounds (isomer A; 60 mg) and (isomer B; 70 mg), together with mixed fractions.

Workup

  1. customThe mixture was quenched with water
  2. concentrationconcentrated in vacuo
  3. customThe residue was partitioned between ethyl acetate and water
  4. customThe organics were collected
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography
  8. washeluting with 1% methanol/dichloromethane

Sources & evidence

ORD record
ord-20feb76d3ff04b90bae4a739867bd762
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

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