Potassium Iodide → 5-chloro-1-{1-[4,4-bis(4-fluorophenyl)butyl]-3-methyl-4-piperidinyl}-1,3-dihydro-2H-benzimidazol-2-one

HRID 1729824Notes

Reaction equation

HRID 1729824 reaction equation
[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[N:6]([CH:10]3[CH2:15][CH2:14][NH:13][CH2:12][CH:11]3[CH3:16])[C:7](=[O:9])[NH:8][C:4]=2[CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[I-].[K+].Cl[CH2:28][CH2:29][CH2:30][CH:31]([C:39]1[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=1)[C:32]1[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=1>O.CC(C)CC(=O)C>[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[N:6]([CH:10]3[CH2:15][CH2:14][N:13]([CH2:28][CH2:29][CH2:30][CH:31]([C:32]4[CH:33]=[CH:34][C:35]([F:38])=[CH:36][CH:37]=4)[C:39]4[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=4)[CH2:12][CH:11]3[CH3:16])[C:7](=[O:9])[NH:8][C:4]=2[CH:3]=1

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 10340Sodium CarbonateHCID 768201,1'-(4-Chlorobutylidene)bis(4-fluorobenzene)HCID 215002835-chloro-1,3-dihydro-1-(3-methyl-4-piperidinyl)-2H-benzimidazol-2-one

Product 1

HCID 215002475-chloro-1-{1-[4,4-bis(4-fluorophenyl)butyl]-3-methyl-4-piperidinyl}-1,3-dihydro-2H-benzimidazol-2-one

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 7909Methyl Isobutyl KetoneSolvent

Procedure

A mixture of 5.3 parts of 5-chloro-1,3-dihydro-1-(3-methyl-4-piperidinyl)-2H-benzimidazol-2-one, 6.4 parts of sodium carbonate, 0.2 parts of potassium iodide and 200 parts of 4-methyl-2-pentanone is stirred and refluxed for 30 minutes with water-separator. After cooling, there are added 7 parts of 1-chloro-4,4-bis(4-fluorophenyl)butane and stirring at reflux temperature is continued for 18 hours. The reaction mixture is cooled, water is added and the layers are separated. The organic phase is dried, filtered and evaporated. Methylbenzene is added to the oily residue and the whole is acidified with a diluted hydrochloric acid solution. After shaking thoroughly, the methylbenzene-phase is decanted and discarded. The aqueous acid phase, together with the residual oil, is alkalized with ammonium hydroxide and the product is extracted again with methylbenzene. The extract is dried, filtered and evaporated. The residue is purified by column-chromatography over silicagel, using a mixture of trichloromethane and 5% of methanol as eluent. The pure fractions are collected and the eluent is evaporated. The residue is crystallized from a mixture of 2,2'-oxybispropane and a small amount of 2-propanol, yielding 5-chloro-1-{1-[4,4-bis(4-fluorophenyl)butyl]-3-methyl-4-piperidinyl}-1,3-dihydro-2H-benzimidazol-2-one; mp. 141.7° C.

Workup

  1. temperatureAfter cooling
  2. stirringstirring
  3. temperatureat reflux temperature
  4. temperatureThe reaction mixture is cooled
  5. customthe layers are separated
  6. customThe organic phase is dried
  7. filtrationfiltered
  8. customevaporated
  9. additionMethylbenzene is added to the oily residue
  10. stirringAfter shaking thoroughly
  11. customthe methylbenzene-phase is decanted
  12. extractionthe product is extracted again with methylbenzene
  13. customThe extract is dried
  14. filtrationfiltered
  15. customevaporated
  16. customThe residue is purified by column-chromatography over silicagel
  17. additiona mixture of trichloromethane and 5% of methanol as eluent
  18. customThe pure fractions are collected
  19. customthe eluent is evaporated
  20. customThe residue is crystallized from a mixture of 2,2'-oxybispropane

Sources & evidence

ORD record
ord-b6f9d58ea6b442de8926c0ed81bce025
Source dataset
uspto-grants-1976_11
Patent number
US03989707

Reaction notes

Loading…