Dimethylformamide → [1-[(4-Fluorophenyl)methyl]-1H-benzimidazol-2-yl][1-[2-(4-methoxyphenyl)ethyl]-4-piperidinyl]methanone

Participants

Reaction Steps

To a stirred, room temperature, mixture of [1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]-4-piperidinylmethanone, mono (trifluoroacetate) (1.82 g, 4.03×10-3 mole), potassium carbonate (1.39 g, 1.00×10-2 mole), and sieve dry DMF (15 ml) was added 1-(2-bromoethyl)-4-methoxybenzene (0.87 g, 4.04×10-3 mole). The reaction was then immersed in an oil bath which had been preheated to ca. 90° C. After being stirred at between 80°-90° C. for 22 hours, the reaction was allowed to cool to room temperature. The reaction was poured into a separatory funnel containing H2O and a 2:1 mixture of ethyl acetate:toluene. The two phases were mixed and the aqueous layer was separated. The organic layer was washed two times with H2O and once with saturated aqueous NaCl before being dried over anhydrous Na2SO4. The drying agent was removed by filtration and the filtrate was evaporated at reduced pressure leaving an oil which was purified by flash chromatography (ethyl acetate). Crystallization from cyclohexane afforded [1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl][1-[2-(4-methoxyphenyl)ethyl]-4-piperidinyl]methanone as off white matted needles: 1.08 g (5%). This material was spectroscopically identical with the previously described product of Example III.

Provenance & Evidence