Monomethyl terephthalate → methyl 4-{[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-phenylpiperidin-1-yl]carbonyl}benzoate

Participants

Reaction Steps

To a mixture of 13.3 mg of tert-butyl[(1R)-1-(1-naphthyl)ethyl][(3-phenylpiperidin-4-yl)methyl]carbamate, 6.3 mg of 4-methoxycarbonyl benzoic acid, 4.7 mg of HOBt, and 1 mL of DMF was added 100 mg of PS-Carbodiimide (Argonaut Technologies, USA) at room temperature, followed by stirring overnight. To the reaction mixture was added 50 mg of MP-Carbonate (Argonaut Technologies, USA), 50 mg of PS-Isocyanate (Argonaut Technologies, USA), and 0.5 mL of DMF at room temperature, followed by stirring for 4 hours, and the reaction mixture was filtered. The filtrate was concentrated under reduced pressure to obtain methyl 4-{[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-phenylpiperidin-1-yl]carbonyl}benzoate as a crude product. To 0.5 mL of a 1,4-dioxane solution of the obtained crude product were added 0.5 mL of a 4 M hydrogen chloride/ethyl acetate solution at room temperature, followed by stirring for 6 hours. The reaction mixture was concentrated under reduced pressure to obtain methyl 4-{[4-({[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-phenylpiperidin-1-yl]carbonyl}benzoate as a crude product. To 0.5 mL of a THF solution of the obtained crude product was added 0.5 mL of methanol and 0.5 mL of a 1 M aqueous sodium hydroxide solution at room temperature, followed by stirring overnight. To the reaction mixture was added 0.5 mL of 1 M hydrochloric acid, followed by concentration under reduced pressure. The obtained residue was purified by preparative high performance liquid chromatography (column: registered trademark SunFire, Waters, particle diameter of 5 μm, inner diameter of 19 mm, and length of 100 mm), flow rate: 25 ml/min., column temperature: 20° C., methanol—a 0.1% aqueous formic acid solution) to obtain 7.7 mg of 4-{[4-({[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-phenylpiperidin-1-yl]carbonyl}benzoic acid.

Provenance & Evidence