Sodium Iodide → (1-(2-(trifluoromethoxy)ethyl)-1H-benzimidazol-2-yl)(1-(t-butoxycarbonyl)piperidin-4-yl)amine

Participants

Reaction Steps

Combine (1H-benzimidazol-2-yl)(1-(t-butoxycarbonyl)piperidin-4-yl)amine (0.158 g, 0.5 mmol) and dimethylformamide (4 mL). Cool in an ice-bath. Add sodium hydride (0.013 g, 60% in oil, 55 mmol). Warm to ambient temperature. After 30 minutes, add a solution of 2-(methanesulfonyloxy)ethyl trifluoromethoxy ether (0.15 g, 0.75 mmol) in dimethylformamide (1 mL). Add sodium iodide (0.11 g, 075 mmol). After 2 hours, heat to 80° C. After 4 hours, cool to ambient temperature. After 18 hours dilute the reaction mixture with ethyl acetate and extract with brine. Dry the organic layer over MgSO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting sequentially with hexane, 30% ethyl acetate/hexane and then 50% ethyl acetate/hexane to give (1-(2-(trifluoromethoxy)ethyl)-1H-benzimidazol-2-yl)(1-(t-butoxycarbonyl)piperidin-4-yl)amine: Rf=0.26 (silica gel, 50% ethyl acetate/hexane).

Provenance & Evidence