1-Methanesulphonyloxy-3-(3,4-dichlorophenyl)-4-[2-(3-trifluoromethyl-4-fluorobenzoyl)imidazol-1-yl]butane → 4-Cyclohexyl-1-(3-[3,4-dichlorophenyl]-4-[2-(3-trifluoromethyl-4-fluorobenzoyl)imidazol-1-yl]butyl)quinuclidinium methanesulphonate

HRID 1533024Notes

Reaction equation

HRID 1533024 reaction equation
[CH3:1][S:2]([O:5][CH2:6][CH2:7][CH:8]([C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[C:30]([Cl:35])[CH:29]=1)[CH2:9][N:10]1[CH:14]=[CH:13][N:12]=[C:11]1[C:15](=[O:27])[C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([C:23]([F:26])([F:25])[F:24])[CH:17]=1)(=[O:4])=[O:3].[CH:36]1([C:42]23[CH2:49][CH2:48][N:45]([CH2:46][CH2:47]2)[CH2:44][CH2:43]3)[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1>C(#N)C>[CH3:1][S:2]([O-:5])(=[O:4])=[O:3].[CH:36]1([C:42]23[CH2:49][CH2:48][N+:45]([CH2:6][CH2:7][CH:8]([C:28]4[CH:33]=[CH:32][C:31]([Cl:34])=[C:30]([Cl:35])[CH:29]=4)[CH2:9][N:10]4[CH:14]=[CH:13][N:12]=[C:11]4[C:15](=[O:27])[C:16]4[CH:21]=[CH:20][C:19]([F:22])=[C:18]([C:23]([F:24])([F:26])[F:25])[CH:17]=4)([CH2:44][CH2:43]2)[CH2:46][CH2:47]3)[CH2:37][CH2:38][CH2:39][CH2:40][CH2:41]1

Participants

4

Reactant 2

HCID 226138101-Methanesulphonyloxy-3-(3,4-dichlorophenyl)-4-[2-(3-trifluoromethyl-4-fluorobenzoyl)imidazol-1-yl]butaneHCID 226138404-Cyclohexylquinuclidine

Product 1

HCID 226137974-Cyclohexyl-1-(3-[3,4-dichlorophenyl]-4-[2-(3-trifluoromethyl-4-fluorobenzoyl)imidazol-1-yl]butyl)quinuclidinium methanesulphonateYield 66.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

1-Methanesulphonyloxy-3-(3,4-dichlorophenyl)-4-[2-(3-trifluoromethyl-4-fluorobenzoyl)imidazol-1-yl]butane (0.77 g) (see Preparation 80) and 4-cyclohexylquinuclidine (0.31 g) (see Preparation 1) were dissolved in acetonitrile (10 ml) and heated under reflux for 5 hours. The solvent was removed under reduced pressure, the resulting residue dissolved in dichloromethane and the solvent removed under reduced pressure. The residue was chromatographed on silica gel eluting with a solvent gradient of 95:5 changing to 80:20, by volume, dichloromethane:methanol to give 4-cyclohexyl-1-(3-[3,4-dichlorophenyl]-4-[2-(3-trifluoromethyl-4-fluorobenzoyl)imidazol-1-yl]butyl)quinuclidinium methanesulphonate (0.69 g) as a white foam.

Workup

  1. temperatureheated
  2. temperatureunder reflux for 5 hours
  3. customThe solvent was removed under reduced pressure
  4. dissolutionthe resulting residue dissolved in dichloromethane
  5. customthe solvent removed under reduced pressure
  6. customThe residue was chromatographed on silica gel eluting with a solvent gradient of 95:5 changing to 80:20, by volume, dichloromethane

Sources & evidence

ORD record
ord-fad1464cfd60499cb4ed08978f41e213
Source dataset
uspto-grants-2001_03
Patent number
US06207678B1

Reaction notes

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