Acetone → 3-(1-butylpiperidin-4-yl)-1H-benzimidazol-2-one

HRID 567783Notes

Reaction equation

HRID 567783 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([N:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[NH:9][C:8]2=[O:16])[CH2:3][CH2:2]1.[CH2:17](Br)[CH2:18][CH2:19][CH3:20].C(=O)([O-])[O-].[K+].[K+].CC(C)=O>C(O)C.C(OCC)C>[CH2:17]([N:1]1[CH2:2][CH2:3][CH:4]([N:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[NH:9][C:8]2=[O:16])[CH2:5][CH2:6]1)[CH2:18][CH2:19][CH3:20]

Participants

7

Reactant 4

HCID 180AcetoneHCID 8002Butyl bromideHCID 11430Potassium CarbonateHCID 886381,3-Dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-one

Product 1

HCID 45496423-(1-butylpiperidin-4-yl)-1H-benzimidazol-2-one

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 3283Diethyl EtherSolvent

Procedure

A mixture of 1-piperidin-4-yl-1,3-dihydro-benzimidazol-2-one (1.96 g, 9 mmol), 1-butylbromide (1.46 ml, 13.5 mmol) and potassium carbonate (1.86 g, 13.5 mmol) in ethanol (20 ml) was refluxed for 18 hours. After cooling to ambient temperature acetone (5 ml) and diethyl ether (5 ml) was added to the reaction mixture, followed by filtration and evaporation of the filtrate in vacuo. The crude product was subjected to column chromatography using a mixture of chloroform and methanol (7/1) containing 1% concentrated ammonium hydroxide as eluent and 1-butyl-3-(1-butyl-piperidin-4-yl)-1,3-dihydro-benzimidazol-2-one was eluted first followed by 1-(1-butyl-piperidin-4-yl)-1,3-dihydro-benzimidazol-2-one contaminated with the di-butylated product. The last product was recrystallized from ethanol and 1-(1-butyl-piperidin-4-yl)-1,3-dihydro-benzimidazol-2-one was isolated as a white crystalline compound, which was dissolved in a small amount of methylene chloride whereafter oxalic acid was added. The formed 1-(1-butyl-piperidin-4-yl)-1,3-dihydro-benzimidazol-2-one oxalate was collected by filtration, white crystals, m.p. 209-214° C. 1-butyl-3-(1-butyl-piperidin-4-yl)-1,3-dihydro-benzimidazol-2-one as an oil was dissolved in a small amount of methylene chloride and oxalic acid was added. Only a yellow syrup of this product was obtained.

Workup

  1. temperaturewas refluxed for 18 hours
  2. additionwas added to the reaction mixture
  3. filtrationfollowed by filtration and evaporation of the filtrate in vacuo
  4. additiona mixture of chloroform and methanol (7/1)
  5. additioncontaining 1% concentrated ammonium hydroxide as eluent
  6. wash1-butyl-3-(1-butyl-piperidin-4-yl)-1,3-dihydro-benzimidazol-2-one was eluted first
  7. customThe last product was recrystallized from ethanol

Sources & evidence

ORD record
ord-57365d77f01d40c29e1c8bd505db1339
Source dataset
uspto-grants-2001_01
Patent number
US06180649B2

Reaction notes

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