Sodium hydride → Tert-butyl [4-[2-(benzimidazol-2-yloxy)ethyl]piperazin-1-yl] carboxylate

HRID 1064874Notes

Reaction equation

HRID 1064874 reaction equation
[OH:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1.[H-].[Na+].C([N:26]1[C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=2[N:28]=[C:27]1Cl)C1C=CC=CC=1>CN(C=O)C>[N:26]1[C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=2[NH:28][C:27]=1[O:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 735736Tert-butyl 4-(2-hydroxyethyl)piperazine-1-carboxylateHCID 38219871-Benzyl-2-chlorobenzimidazole

Product 1

HCID 86591243Tert-butyl [4-[2-(benzimidazol-2-yloxy)ethyl]piperazin-1-yl] carboxylateYield 106.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of tert-butyl 4-(2-hydroxyethyl)-1-piperazinecarboxylate (230 mg, 1.00 mmol) in DMF (2 ml) was added sodium hydride (55%, 52 mg, 1.19 mmol) with ice-cooling and stirred at 75° C. for 30 minutes, and then added 1-benzyl-2-chlorobenzimidazole (243 mg, 1.00 mmol) and stirred at 75° C. for 24 hours. The reaction solution was concentrated in vacuo, and the resulting residue was dissolved in chloroform. The organic layer was washed with water and a saturated sodium chloride solution successively, dried over anhydrous sodium sulfate and concentrated in vacuo. The resulting residue was purified by a silica gel column chromatography (silica gel 25 g, developing solvent; hexane:ethyl acetate=5:1 1:1) to provide 369 mg (yield 85%) of tert-butyl [4-[2-(benzimidazol-2-yloxy)ethyl]piperazin-1-yl]carboxylate as colorless solid.

Workup

  1. temperaturecooling
  2. concentrationThe reaction solution was concentrated in vacuo
  3. dissolutionthe resulting residue was dissolved in chloroform
  4. washThe organic layer was washed with water
  5. dry with materiala saturated sodium chloride solution successively, dried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified by a silica gel column chromatography (silica gel 25 g, developing solvent; hexane:ethyl acetate=5:1 1:1)

Sources & evidence

ORD record
ord-865c64db3c5743e4beb6ef167e1fd6c3
Source dataset
uspto-grants-2005_11
Patent number
US06969711B2

Reaction notes

Loading…