Hydrochloric Acid → 3-(4-{[4-({5-(2-phenylethyl)-3-[4-(trifluoromethyl)phenyl]-1H-pyrazol-1-yl}methyl)benzyl]oxy}phenyl)propanoic acid

Participants

Reaction Steps

A mixture of 5-(2-phenylethyl)-3-[4-(trifluoromethyl)phenyl]-1H-pyrazole (350 mg, 1.11 mmol), sodium hydride (60% in oil, 40 mg, 1.00 mmol) and N,N-dimethylformamide (5 mL) was stirred at room temperature for 1 hr. Methyl 3-(4-([4-(chloromethyl)benzyl]oxy)phenyl)propanoate (318 mg, 1.00 mmol) was added to the reaction mixture at room temperature and the mixture was further stirred at room temperature for 1 hr. The reaction mixture was poured into 1N hydrochloric acid, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was dried using a Presep Dehydration tube (Manufactured by Wako Pure Chemical Industries, Ltd.), and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=19:1-1:1) to give a yellow oil. The yellow oil was dissolved in a mixed solvent of methanol (5 mL) and tetrahydrofuran (5 mL), and 2 N aqueous sodium hydroxide solution (2 mL) was added. The mixture was stirred at room temperature for 1 hr. The reaction mixture was diluted with water, and neutralized with 1 N hydrochloric acid. The mixture was extracted with ethyl acetate. The ethyl acetate layer was dried using a Presep Dehydration tube (Manufactured by Wako Pure Chemical Industries, Ltd.), and concentrated under reduced pressure to give the title compound (550 mg, yield 75%) as colorless crystals. MS: m/z 585 (MH+), 1H NMR (CDCl3) δ: 2.58-2.67 (2H, m), 2.80-2.94 (6H, m), 5.00 (2H, s), 5.26 (2H, s), 6.46 (1H, s), 6.86 (2H, d, J=8.9 Hz), 7.06-7.14 (6H, m), 7.18-7.32 (3H, m), 7.36 (2H, d, J=8.3 Hz), 7.63 (2H, d, J=8.1 Hz), 7.90 (2H, d, J=8.1 Hz).

Provenance & Evidence