Hydrochloric Acid → 4-{[(4-tert-Butylcyclohexyl)(1-methyl-1H-benzimidazol-2-yl)amino]methyl}-benzoic acid

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Reaction Steps

To the title compound from Example 1 Step C (0.72 mmol, 300 mg) in 5 mL of THF was added MeI (1 mmol, 67 μL), followed by NaH (1 mmol, 40 mg of 60% dispersion in mineral oil) (exothermic, H2 evolution). After 1 h starting benzimidazole was still present, so the reaction was treated with additional MeI (1 mmol) and NaH (1 mmol). After 1 h the reaction was complete (HPLC A: 2.38). The mixture was concentrated under reduced pressure and the residue was taken up in 6 mL of dioxane. A solution of LiOH (7 mmol, 172 mg) in 2 mL of H2O was added and the resulting mixture was stirred at ambient temperature overnight. The mixture was poured into EtOAc/H2O, and acidified with 2 N HCl until two clear layers formed after agitation. The organic layer was collected and the aqueous layer was washed with EtOAc. The combined organic phase was dried with MgSO4 and concentrated under reduced pressure affording product as a yellow solid. MS (ESI): m/z 420 (M+H). HPLC A: 2.09 min.

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