[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]1A 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+).
Loading…
