Cesium carbonate → 2-[2-Chloro-5-(3-ethoxycarbonyl-pyrrolidin-1-yl)-phenyl]-5-methyl-benzoimidazole-1-carboxylic acid tert-butyl ester

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Reaction Conditions

Reaction Steps

Method 5—Step a 2-(5-Bromo-2-chloro-phenyl)-5-methyl-benzoimidazole-1-carboxylic acid tert-butyl ester (obtained as described in general method 4, step c) (1.80 g, 4.28 mmol), pyrrolidine-3-carboxylic acid methyl ester (0.92 g, 5.56 mmol) and cesium carbonate (6.95 g, 21.38 mmol) were to a dry flask under nitrogen containing palladium acetate (0.19 g, 0.86 mmol) and BINAP (0.80 g, 1.28 mmol) in dry toluene (11 mL) and previously stirred for 20 minutes under nitrogen. The reaction mixture was heated at 80° C. overnight, cooled to room temperature, diluted with AcOEt (40 mL), salts were filtered off, the organic layer washed with water (1×30 mL) and brine (1×20 mL), dried over Na2SO4 and then concentrated under reduced pressure. To the crude a mixture of solvents cyclohexane:AcOEt/4:1 (15 mL) was added and filtered through a column with Na2SO4 to remove all the salts, washed with the mixture of solvents and the organic layer purified by flash chromatography (eluent: cyclohexane:AcOEt/4:1) to afford 1.71 g of the title compound (86%).

Provenance & Evidence