Hydrochloric Acid → Methyl (3S)-3-(3-isoxazolyl)-3-(4-(((3-methyl-5-(4-(trifluoromethyl)phenyl)-2-thienyl)methyl)oxy)phenyl)propanoate

Participants

Reaction Conditions

Reaction Steps

To a solution of 62.8 (94 mg, 0.15 mmol) in THF (1.5 mL) were added 30% H2O2 (0.17 mL, 1.50 mmol) and 1N LiOH (0.73 mL, 0.73 mmol) at 0° C. The mixture was stirred for 1 hour at 0° C., adjusted to pH 3 with aqueous HCl, and extracted with EtOAc. The combined organics were washed with 1N Na2SO3 (pH 3) and brine, dried (Na2SO4), and concentrated. The residue was dissolved in 9:1 MeCN/DMF (1.5 mL), and to the solution were added K2CO3 (30 mg, 0.22 mmol) and iodomethane (20 μL, 0.22 mmol). The mixture was stirred overnight at room temperature, diluted with EtOAc, washed with water and brine, dried (Na2SO4), and concentrated. The crude product was chromatographed on silica gel (0-40% EtOAc/hexane) to afford 62.9 (64 mg, 88%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3) δ 8.28 (d, 1H), 7.65 (d, 2H), 7.60 (d, 2H), 7.20 (d, 2H), 7.15 (s, 1H), 6.95 (d, 2H), 6.08 (d, 1H), 5.10 (s, 2H), 4.59 (t, 1H), 3.64 (s, 3H), 3.31 (dd, 1H), 2.95 (dd, 1H), 2.28 (s, 3H).

Provenance & Evidence