Hydrochloric Acid → 3-(4-((5-(2-(3,4-Dichlorophenyl)propan-2-yl)-1-(4-fluoro-3-methoxyphenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorobenzamido)propanoic acid

Participants

Reaction Steps

A solution of methyl 3-(4-((5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluoro-3-methoxyphenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorobenzamido)propanoate (0.85 mmol from previous step) in MeOH (10 mL) was treated with a solution of NaOH (0.6 mL of a 5M aqueous solution, 3 mmol) at ambient temperature. After stirring for 100 min, the reaction mixture was added dropwise to 1N HCl. The addition afforded a thick, white oil that separated from the aqueous acid. The aqueous mixture was extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4 and concentrated under reduced pressure to afford crude product. This material was purified by flash chromatography (silica gel, MeOH/DCM, 0:100 to 10:90) to afford the title compound (220 mg, 40% yield over three steps) as a white powder. 1H NMR (400 MHz, CDCl3) δ 7.29 (dt, J=9.4, 6.0 Hz, 5H), 7.07 (d, J=2.2 Hz, 1H), 6.95 (dd, J=10.5, 8.6 Hz, 1H), 6.82 (dd, J=8.4, 2.2 Hz, 1H), 6.34-6.25 (m, 1H), 5.94 (dd, J=7.4, 2.4 Hz, 1H), 3.96 (s, 2H), 3.76-3.67 (m, 2H), 3.53 (s, 3H), 2.65 (s, 2H), 1.54 (s, 3H), 1.48 (s, 3H); MS (EI) m/z 652 (MH+).

Provenance & Evidence