Sodium hydride → 2-(4-Chlorophenoxymethyl)-4-[5-[1-(t-butoxycarbonyl)piperidin-4-yl]pentoxy]-1-[5-[1-(t-butoxycarbonyl)piperidin-4-yl]pentyl]benzimidazole

Participants

Reaction Steps

A solution of 4-hydroxy-2-(4-chlorophenoxymethyl)benzimidazole (500 mg, 1.82 mmol) in dry N,N-dimethylformamide (8 ml) was treated with sodium hydride (60% in mineral oil, 162 mg, 4.0 mmol, 2.2 eq). The resulting mixture was stirred at room temperature under a stream of nitrogen for about one hour. To this reaction mixture 5-[1-(t-butoxycarbonyl)piperidin-4-yl)pentyl bromide (4.0 mmol, 2.2 eq) was added and the resulting mixture was stirred for three hours at 70° C. The reaction was quenched by the addition of 10 ml of water. The aqueous fraction was extracted with ethyl acetate (3×10 ml). The organic fractions were combined and washed with water (2×10 ml), and then brine (1×10 ml), and then dried over magnesium sulfate. The solvents were removed in vacuo to yield a light brownish crude material. The desired title product was further purified by flash chromatography. There is some substitution at the 7-position of the benzimidazole present, although the 4-substituted is the major isomer.

Provenance & Evidence