Methyl iodide → (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

HRID 2088203Notes

Reaction equation

HRID 2088203 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:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[C@H:10]([O:21][CH2:22][C:23]1[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[C:25]([C:33]([F:36])([F:35])[F:34])[CH:24]=1)[CH2:11][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CI.[C:45](=O)([O-])[O-].[K+].[K+]>C(#N)C>[CH2:1]([N:8]1[C@@H:13]2[C@H:14]([C:16]3[N:20]=[N:19][N:18]([CH3:45])[N:17]=3)[CH2:15][C@@:9]1([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[C@H:10]([O:21][CH2:22][C:23]1[CH:24]=[C:25]([C:33]([F:36])([F:35])[F:34])[CH:26]=[C:27]([C:29]([F:30])([F:31])[F:32])[CH:28]=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 178506223HCID 178506223, compound

Product 1

HCID 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

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

(1R*,2R*,5S*,6R*)-8-Benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-1-phenyl-6-(tetrazol-5-yl)-8-azabicyclo[3.2.1]octane (Example 138; 0.5 g, 0.85 mmol), methyl iodide (0.3 g, 2.1 mmol) and potassium carbonate (0.29 g, 2.1 mmol) were stirred at 50° C. in acetonitrile (20 ml) for 2 hours. Concentrated in vacuo then partitioned between dichloromethane and water. The organic layer was separated, dried (MgSO4), filtered and concentrated. The residue was chromatographed on silica gel eluting with 20, 50 and 75% ethyl acetate/iso-hexanes to afford the title compounds: isomer A (0.25 g, 49%) and isomer B (0.17 g, 33%).

Workup

  1. concentrationConcentrated in vacuo
  2. customthen partitioned between dichloromethane and water
  3. customThe organic layer was separated
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was chromatographed on silica gel eluting with 20, 50 and 75% ethyl acetate/iso-hexanes

Sources & evidence

ORD record
ord-da011d4d542049799a36b3db39f91214
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

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