Benzimidazole → methyl 4-[(1H-benzoimidazol-1-yl)methyl]benzoate

HRID 1716821Notes

Reaction equation

HRID 1716821 reaction equation
[N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[NH:3][CH:2]=1.[H-].[Na+].Br[CH2:13][C:14]1[CH:23]=[CH:22][C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:16][CH:15]=1>C1COCC1.CN(C=O)C.CCOC(C)=O>[N:1]1([CH2:13][C:14]2[CH:23]=[CH:22][C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:16][CH:15]=2)[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1

Participants

6

Reactant 3

HCID 5798BenzimidazoleHCID 24758Sodium hydrideHCID 256687Methyl 4-(bromomethyl)benzoate

Product 1

HCID 2823606methyl 4-[(1H-benzoimidazol-1-yl)methyl]benzoate

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Procedure

A solution of benzimidazole (5 mmol, 0.97 g) in THF/DMF (5:1, 20 mL) is treated with sodium hydride (0.5 g), stirred for 10 minutes at room temperature, treated with methyl 4-(bromomethyl)benzoate (1.4 g, 6 mmol) and stirred at room temperature overnight. The reaction mixture is diluted with EtOAc, washed with saturated NaHCO3, dried over MgSO4 and concentrated in vacuo to give methyl 4-[(1H-benzoimidazol-1-yl)methyl]benzoate as a solid residue. The residue is dissolved in MeOH/water (2:1), treated with lithium hydroxide (0.42 g, 10 mmol), stirred at room temperature overnight, evaporated to remove the MeOH. The resultant concentrate is diluted with 1N sodium hydroxide (50 mL), washed with EtOAc, acidified with concentrated HCl and extracted with EtOAc. The extracts were combined, dried over MgSO4 and concentrated to dryness to give the title product in 75% yield, identified by NMR and mass spectral analyses. 1H NMR (400 MHz, DMSO-d6): 8.08 (s, 1H); 7.99 (d, J=8 Hz, 2H); 7.78 (d, J=8 Hz, 1H); 7.24-7.27 (m, 5H); 5.49 (s, 2H). LCMS (ESI+) 253 (MH+).

Workup

  1. stirringstirred at room temperature overnight
  2. washwashed with saturated NaHCO3
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-bad1ce5a075944df9c3971aaee73bd58
Source dataset
uspto-grants-2010_09
Patent number
US07803825B2

Reaction notes

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