Hydrochloric Acid → 3-[2-Fluoro-4-({4-[([2-(4-fluorophenyl)ethyl]{4-[4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl}amino)methyl]-benzyl}oxy)phenyl]propanoic acid

Participants

Reaction Steps

To a solution of N-[2-(4-fluorophenyl)ethyl]-4-[4-(trifluoromethyl)phenyl]-1,3-thiazole-2-amine (500 mg, 1.36 mmol) in N,N-dimethylformamide (5 mL) was added sodium hydride (40 mg, in oil, 1.0 mmol) at room temperature, and the mixture was stirred at room temperature for 1 hr. Ethyl 3-(4-{[4-(chloromethyl)benzyl]oxy}-2-fluorophenyl)propanoate (350 mg, 1.0 mmol) was added, and the mixture was further stirred at room temperature for 1 hr. The reaction mixture was poured into 1N hydrochloric acid and extracted with ethyl acetate. The organic layer was concentrated. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:19-1:1 in volume ratio) give a yellow oil. The oil was dissolved in a mixed solvent of ethanol (5 mL) and tetrahydrofuran (5 mL), and 2N aqueous sodium hydroxide solution (2 mL) was added. The mixture was stirred at room temperature for 2 hr. The reaction mixture was poured into 1N hydrochloric acid, and the mixture was extracted with ethyl acetate. The organic layer was concentrated, and the residue was purified by preparative HPLC. The obtained fraction was concentrated, neutralized with 10% aqueous sodium hydrogencarbonate solution and extracted with ethyl acetate. The ethyl acetate layer was filtered with a Presep Dehydration tube (manufactured by Wako Pure Chemical Industries, Ltd.) and concentrated to give the title compound (139 mg, yield 21%, 2 steps) as a yellow oil.

Provenance & Evidence