4-Piperidinecarboxylic acid → 1-[3-(1-Methyl-1H-benzoimidazol-2-yl)-phenyl]-piperidine-4-carboxylic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

Method 11—Step a 2-(3-Bromo-phenyl)-1-methyl-1H-benzoimidazole (obtained as described in general method 1, step b) (5.00 g, 17.40 mmol), piperidine-4-carboxylic acid esthyl ester (3.56 g, 22.62 mmol) and cesium carbonate (28.34 g, 87 mmol) were placed into a round bottom flask under nitrogen. At the same time palladium acetate (0.79 g, 3.48 mmol), and BINAP (3.33 g, 5.22 mmol) were placed into a flask under nitrogen. Then dry toluene (18 mL) was added and the mixture was stirred 20 minutes under nitrogen before being added to the first flask. The reaction mixture was heated at 80° C. for two days, then diluted with ethyl acetate (100 mL), filtered through Na2SO4, and washed with water (2×50 mL) and brine (1×50 mL). The organic solution was concentrated under reduced pressure and crude was purified by flash chromatography (eluent: cyclohexane:AcOEt/4:1) to afford 3.45 g of the title compound (55%).

Provenance & Evidence