Ethyl 4-piperidinecarboxylate → 5-Chloro-2-[5-(4-ethoxycarbonyl-piperidin-1-yl)-2-fluoro-phenyl]-benzoimidazole-1-carboxylic acid tert-butyl ester

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Reaction Conditions

Reaction Steps

Method 10—Step a 2-(5-Bromo-2-fluoro-phenyl)-5-chloro-benzoimidazole-1-carboxylic acid tert-butyl ester (obtained as described in general method 7, step c) (1.06 g, 2.50 mmol), Pd2(dba)3 (0.36 g, 0.50 mmol), 2-di-t-butylphosphino-2′,4′,6′-tri-1-propyl-1,1′biphenyl (t-BuXphos) (0.32 g, 0.75 mmol) and sodium tert-butoxide (0.48 g, 5.00 mmol) were placed into a dried vial and few cycles of vacuum/nitrogen were performed. Then dry toluene (5 mL) and piperidine-4-carboxylic acid ethyl ester (0.50 mL, 3.25 mmol) were added, the reaction mixture was heated at 85° C. overnight, and washed with saturated Na2CO3 solution (3×5 mL) and water (3×3 mL). The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure, and the crude was purified by flash chromatography (eluent: gradient from EtOAc:cyclohexane/1:5 to 1:2) to obtain 0.30 g of the title compound (24%).

Provenance & Evidence