5-Chloro-1,3-dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-one → Clopimozide

HRID 1729810Notes

Reaction equation

HRID 1729810 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][CH3:11])=[CH:4][CH:3]=1.[Cl:12][C:13]1[CH:28]=[CH:27][C:16]2[N:17]([CH:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)[C:18](=[O:20])[NH:19][C:15]=2[CH:14]=1.C(=O)(O)[O-].[Na+]>C(O)C>[Cl:12][C:13]1[CH:28]=[CH:27][C:16]2[N:17]([CH:21]3[CH2:22][CH2:23][N:24]([CH2:11][CH2:10][CH2:9][CH:8]([C:5]4[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=4)[C:5]4[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=4)[CH2:25][CH2:26]3)[C:18](=[O:20])[NH:19][C:15]=2[CH:14]=1

Participants

5

Reactant 3

HCID 1046075-Chloro-1,3-dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-oneHCID 140728Benzene, 1-butyl-4-fluoro-HCID 516892Sodium Bicarbonate

Product 1

HCID 65449Clopimozide

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 5 parts of 1-chloro-4,4-bis(p-fluorophenyl-butane 3.8 parts of 5-chloro-1-(4-piperidyl)-2-benzimidazolinone, 1.4 parts of sodium bicarbonate and 80 parts of absolute ethanol is stirred and refluxed for 24 hours. The reaction mixture is evaporated. Water and toluene are added to the residue and the whole is shaken vigorously. The layers are separated and the toluene layer is dried, filtered and evaporated. The oily residue is purified by column-chromatography over silicagel, using a mixture of chloroform and 5% of methanol as eluent. The pure fractions are collected and the eluent is evaporated. The oily residue is triturated in diisopropylether. The solid product is filtered off and crystallized from 4-methyl-2-pentanone, yielding 5-chloro-1{1-[4,4-bis(p-fluorophenyl)butyl]-4-piperidyl}-2-benzimidazolinone; mp. 185.8° C.

Workup

  1. temperaturerefluxed for 24 hours
  2. customThe reaction mixture is evaporated
  3. additionWater and toluene are added to the residue
  4. stirringthe whole is shaken vigorously
  5. customThe layers are separated
  6. dry with materialthe toluene layer is dried
  7. filtrationfiltered
  8. customevaporated
  9. customThe oily residue is purified by column-chromatography over silicagel
  10. additiona mixture of chloroform and 5% of methanol as eluent
  11. customThe pure fractions are collected
  12. customthe eluent is evaporated
  13. customThe oily residue is triturated in diisopropylether
  14. filtrationThe solid product is filtered off
  15. customcrystallized from 4-methyl-2-pentanone

Sources & evidence

ORD record
ord-324392a17af841b8ac297a9ea78ea5be
Source dataset
uspto-grants-1976_11
Patent number
US03989707

Reaction notes

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