Potassium Iodide → 1-[4-(1,1-dimethylethyl)phenyl]-4-[4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]carbonyl]-1-piperidinyl]-1-butanone

HRID 1647049Notes

Reaction equation

HRID 1647049 reaction equation
FC(F)(F)C(O)=O.[F:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][N:16]2[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=3[N:18]=[C:17]2[C:25]([CH:27]2[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]2)=[O:26])=[CH:11][CH:10]=1.Cl[CH2:34][CH2:35][CH2:36][C:37]([C:39]1[CH:44]=[CH:43][C:42]([C:45]([CH3:48])([CH3:47])[CH3:46])=[CH:41][CH:40]=1)=[O:38].C(=O)(O)[O-].[K+].[I-].[K+]>C1(C)C=CC=CC=1.O>[CH3:48][C:45]([C:42]1[CH:41]=[CH:40][C:39]([C:37](=[O:38])[CH2:36][CH2:35][CH2:34][N:30]2[CH2:31][CH2:32][CH:27]([C:25]([C:17]3[N:16]([CH2:15][C:12]4[CH:13]=[CH:14][C:9]([F:8])=[CH:10][CH:11]=4)[C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=4[N:18]=3)=[O:26])[CH2:28][CH2:29]2)=[CH:44][CH:43]=1)([CH3:46])[CH3:47]

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 516893Potassium BicarbonateHCID 27236944'-tert-Butyl-4-chlorobutyrophenoneHCID 701016654-(1-(4-Fluoro-benzyl)-1h-benzoimidazole-2-carbonyl)-piperidine trifluoroacetic acid salt

Product 1

HCID 198004991-[4-(1,1-dimethylethyl)phenyl]-4-[4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]carbonyl]-1-piperidinyl]-1-butanone

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]-4-piperidinylmethanone mono (trifluoroacetate) (5.0 g, 11 mmol), 4-chloro-4'-tert-butylbutyrophenone (6.2, 26 mmol), potassium bicarbonate (2.5 g, 25 mmol), and potassium iodide (catalytic amount) were combined and refluxed in toluene (50 ml) and water (5 ml) for 3 days. The cooled layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with water, brine, dried (MgSO4), and concentrated. The resulting oil was chromatographed on silica gel (75×160 mm), eluting with ethyl acetate. The appropriate fractions were combined, concentrated, and the resulting oil crystallized from cyclohexane to afford 1-[4-(1,1-dimethylethyl)phenyl]-4-[4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol -2-yl]carbonyl]-1-piperidinyl]-1-butanone: 3.4 g (57%), m.p. 105-106° C.

Workup

  1. customThe cooled layers were separated
  2. extractionthe aqueous layer was extracted with ethyl acetate
  3. washThe combined organic layers were washed with water, brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customThe resulting oil was chromatographed on silica gel (75×160 mm)
  7. washeluting with ethyl acetate
  8. concentrationconcentrated
  9. customthe resulting oil crystallized from cyclohexane

Sources & evidence

ORD record
ord-4b36d2be58be45d998e2219efe222360
Source dataset
uspto-grants-1993_01
Patent number
US05182399

Reaction notes

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