2-Morpholineacetic acid → 2-(4-(2-Hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)morpholin-2-yl)acetic acid

Participants

Reaction Steps

To a mixture of 3-(4-(oxiran-2-yl)phenyl)-5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazole, Preparation 28C (25 mg, 0.063 mmol) in 2-propanol (2 mL) and DMSO (1 mL) was added 2-(morpholin-2-yl)acetic acid (18.18 mg, 0.125 mmol). The reaction mixture was hated at 80° C. overnight. The crude material was purified via preparative LC/MS with the following conditions: Column: Waters XBridge C18, 19×250 mm, 5-μm particles; Guard Column: Waters XBridge C18, 19×10 mm, 5-μm particles; Mobile Phase A: 5:95 acetonitrile:water with 10-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 10-mM ammonium acetate; Gradient: 15-100% B over 25 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation. The yield of the desired product was 12.8 mg, and its purity was 99%. 1H NMR (400 MHz, MeOD) δ ppm 8.18 (2H, d, J=8.28 Hz), 7.38-7.86 (7H, m), 5.03 (1H, ddd, J=9.03, 4.39, 4.14 Hz), 3.97-4.11 (1H, m), 3.90 (1H, t, J=9.66 Hz), 3.69-3.84 (1H, m), 2.97-3.21 (2H, m), 2.69-2.93 (2H, m), 2.18-2.63 (4H, m). MS (m+1)=545.

Provenance & Evidence