4-Phenyl-1-azabicyclo(2.2.2)octane → 4-Phenyl-1-(3-[3,4-dichlorophenyl]-4-{2-[3,5-bis(trifluoromethyl)benzoyl]imidazol-1-yl}butyl)quinuclidinium chloride

HRID 844540Notes

Reaction equation

HRID 844540 reaction equation
CS(O[CH2:6][CH2:7][CH:8]([C:31]1[CH:36]=[CH:35][C:34]([Cl:37])=[C:33]([Cl:38])[CH:32]=1)[CH2:9][N:10]1[CH:14]=[CH:13][N:12]=[C:11]1[C:15](=[O:30])[C:16]1[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([C:26]([F:29])([F:28])[F:27])[CH:17]=1)(=O)=O.[C:39]1([C:45]23[CH2:52][CH2:51][N:48]([CH2:49][CH2:50]2)[CH2:47][CH2:46]3)[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1>C(#N)C>[Cl-:37].[C:39]1([C:45]23[CH2:52][CH2:51][N+:48]([CH2:6][CH2:7][CH:8]([C:31]4[CH:36]=[CH:35][C:34]([Cl:37])=[C:33]([Cl:38])[CH:32]=4)[CH2:9][N:10]4[CH:14]=[CH:13][N:12]=[C:11]4[C:15](=[O:30])[C:16]4[CH:17]=[C:18]([C:26]([F:29])([F:28])[F:27])[CH:19]=[C:20]([C:22]([F:24])([F:23])[F:25])[CH:21]=4)([CH2:47][CH2:46]2)[CH2:49][CH2:50]3)[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1

Participants

4

Reactant 2

HCID 1428104-Phenyl-1-azabicyclo(2.2.2)octaneHCID 226138441-Methanesulphonyloxy-3-(3,4-dichlorophenyl)-4-{2-[3,5-bis(trifluoromethyl)benzoyl]imidazol-1-yl}butane

Product 1

HCID 226138184-Phenyl-1-(3-[3,4-dichlorophenyl]-4-{2-[3,5-bis(trifluoromethyl)benzoyl]imidazol-1-yl}butyl)quinuclidinium chlorideYield 87.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

1-Methanesulphonyloxy-3-(3,4-dichlorophenyl)-4-{2-[3,5-bis(trifluoromethyl)benzoyl]imidazol-1-yl}butane (0.7 g) (see Preparation 85) and 4-phenylquinuclidine (0.32 g) (see J. Org. Chem., 22, 1484,(1957)) were dissolved in acetonitrile (10 ml) and the mixture heated under reflux for 18 hours. The solvent was removed under reduced pressure and the resulting residue dissolved in dichloromethane and washed twice with 2N aqueous hydrochloric acid solution. The organic phase was then dried over anhydrous sodium sulphate and the solvent removed under reduced pressure to give a residue which was chromatographed on silica gel eluting with a solvent gradient of 95:5 changing to 90:10, by volume, dichloromethane:methanol to give 4-phenyl-1-(3-[3,4-dichlorophenyl]-4-{2-[3,5-bis(trifluoromethyl)benzoyl]imidazol-1-yl}butyl)quinuclidinium chloride (0.37 g) as a white foam.

Workup

  1. temperaturethe mixture heated
  2. temperatureunder reflux for 18 hours
  3. customThe solvent was removed under reduced pressure
  4. dissolutionthe resulting residue dissolved in dichloromethane
  5. washwashed twice with 2N aqueous hydrochloric acid solution
  6. dry with materialThe organic phase was then dried over anhydrous sodium sulphate
  7. customthe solvent removed under reduced pressure
  8. customto give a residue which
  9. customwas chromatographed on silica gel eluting with a solvent gradient of 95:5 changing to 90:10, by volume, dichloromethane

Sources & evidence

ORD record
ord-e85a767ebb13487bbf282110e4aa2643
Source dataset
uspto-grants-2002_04
Patent number
US06380396B1

Reaction notes

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