Sodium hydride → 4-(Prop-2-enyl)-2-[(4-chlorophenoxy)methyl]-1-[3-[1-(t-butoxycarbonyl)piperidin-4-yl]propyl]benzimidazole

HRID 1384010Notes

Reaction equation

HRID 1384010 reaction equation
[CH2:1]([C:4]1[C:12]2[NH:11][C:10]([CH2:13][O:14][C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=3)=[N:9][C:8]=2[CH:7]=[CH:6][CH:5]=1)[CH:2]=[CH2:3].[H-].[Na+].[C:24]([O:28][C:29]([N:31]1[CH2:36][CH2:35][CH:34]([CH2:37][CH2:38][CH2:39]Br)[CH2:33][CH2:32]1)=[O:30])([CH3:27])([CH3:26])[CH3:25]>CN(C)C=O>[CH2:1]([C:4]1[C:12]2[N:11]=[C:10]([CH2:13][O:14][C:15]3[CH:16]=[CH:17][C:18]([Cl:21])=[CH:19][CH:20]=3)[N:9]([CH2:39][CH2:38][CH2:37][CH:34]3[CH2:35][CH2:36][N:31]([C:29]([O:28][C:24]([CH3:25])([CH3:27])[CH3:26])=[O:30])[CH2:32][CH2:33]3)[C:8]=2[CH:7]=[CH:6][CH:5]=1)[CH:2]=[CH2:3]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 18409081tert-Butyl 4-(3-bromopropyl)piperidine-1-carboxylateHCID 178438906HCID 178438906, compound

Product 1

HCID 211888214-(Prop-2-enyl)-2-[(4-chlorophenoxy)methyl]-1-[3-[1-(t-butoxycarbonyl)piperidin-4-yl]propyl]benzimidazole

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In a 100 ml round bottom flask, under a nitrogen atmosphere, were added 4-(prop-2-enyl)-2-[(4-chlorophenoxy)methyl]benzimidazole (550 mg, 1.84 mmol) and anhydrous N,N-dimethylformamide (59 ml). To this solution was added sodium hydride (60% in mineral oil, 81.04 mg, 2.03 mmol). The resulting mixture was stirred at room temperature for 60 minutes, and then 3-[1-(t-butoxycarbonyl)piperidin-4-yl]propyl bromide (620 mg, 2.03 mmol) was added. The resulting mixture was heated to 100° C. and stirred at this temperature for about three hours. The progress of the reaction was monitored by thin layer chromatography. The reaction mixture was partitioned between ethyl acetate and brine. The aqueous fraction was extracted twice with brine. The organic fractions were combined and dried over sodium sulfate. The solvents were removed in vacuo. The desired title product was further purified by radial chromatography.

Workup

  1. temperatureThe resulting mixture was heated to 100° C.
  2. stirringstirred at this temperature for about three hours
  3. customThe reaction mixture was partitioned between ethyl acetate and brine
  4. extractionThe aqueous fraction was extracted twice with brine
  5. dry with materialdried over sodium sulfate
  6. customThe solvents were removed in vacuo
  7. customThe desired title product was further purified by radial chromatography

Sources & evidence

ORD record
ord-12d45b4e260b43c9afa741f47068d76f
Source dataset
uspto-grants-2001_07
Patent number
US06255494B1

Reaction notes

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