Citric Acid → Tert-butyl 4-(2-(2-(benzyloxy)-5-((1-(tert-butoxycarbonyl)piperidin-4-yl)oxy)benzamido)-4-phenylbenzoyloxy)piperidine-1-carboxylate

Participants

Reaction Steps

1-(tert-Butoxycarbonyl)-4-hydroxypiperidine (0.047 g), cesium carbonate (0.075 g), 1,10-phenanthroline (4.2 mg), and copper(I) iodide (2.2 mg) were added to a toluene (1 mL) solution of tert-butyl 2-(2-(benzyloxy)-5-iodobenzamido)-4-phenylbenzoate (0.070 g), followed by heating to reflux under a nitrogen atmosphere for 4 hours. The reaction mixture was cooled to room temperature, and then 1-(tert-butoxycarbonyl)-4-hydroxypiperidine (0.047 g), cesium carbonate (0.075 g), 1,10-phenanthroline (4.2 mg), and copper(I) iodide (2.2 mg) were added to the reaction mixture, followed by heating to reflux under a nitrogen atmosphere for 2 hours. The reaction mixture was cooled to room temperature, and then 1,10-phenanthroline (4.2 mg) and copper(I) iodide (2.2 mg) were added to the reaction mixture, followed by heating to reflux under a nitrogen atmosphere for 5 hours and 30 minutes. The reaction mixture was cooled to room temperature, and then a 10% aqueous solution of citric acid and ethyl acetate were added thereto. The insoluble substance was removed by filtration. The organic layer was separated, washed with a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography [Kanto Chemical Co., Inc., silica gel 60 (spherical), eluent: 95-60% hexane/ethyl acetate] to obtain 0.074 g of tert-butyl 4-(2-(2-(benzyloxy)-5-((1-(tert-butoxycarbonyl)piperidin-4-yl)oxy)benzamido)-4-phenylbenzoyloxy)piperidine-1-carboxylate.

Provenance & Evidence