Cesium carbonate → 2-(1-(2-Hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidin-3-yl)-2-methylpropanoic acid

Participants

Reaction Conditions

Reaction Steps

To a mixture of (S)-3-(4-(oxiran-2-yl)phenyl)-5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazole, Preparation 28C-peak 1 (30 mg, 0.075 mmol) and ethyl 2-methyl-2-(piperidin-3-yl)propanoate (14.97 mg, 0.075 mmol) in EtOH (10 mL) was added cesium carbonate (147 mg, 0.451 mmol). The reaction mixture was heated at 80° C. overnight. The reaction mixture was filtered and purified by HPLC. HPLC conditions: PHENOMENEX® Luna C18 5 micron column (250×30 mm); 25-100% CH3CN/water (0.1% TFA); 25 minute gradient; 30 mL/min. Fractions with correct mass were isolated and concentrated in vacuo. This residue was heated in 6N HCl/dioxane (1:1) at 60° C. for 3 days. The reaction mixture was filtered and purified by HPLC. HPLC conditions: PHENOMENEX® Luna C18 5 micron column (250×30 mm); 25-100% CH3CN/water (0.1% TFA); 25 minute gradient; 30 mL/min. Fractions with correct mass were isolated and freeze-dried overnight. Obtained 6 mg of 2-(1-((S)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidin-3-yl)-2-methylpropanoic. 1H NMR (400 MHz, MeOD) δ ppm 8.14 (2H, d, J=8.36 Hz), 7.57-7.64 (4H, m), 7.44-7.55 (3H, m), 5.09-5.27 (1H, m), 3.70 (2H, d, J=10.34 Hz), 3.57 (1H, br. s.), 3.23-3.27 (2H, m), 2.79-2.97 (1H, m), 1.73-1.95 (2H, m), 1.24-1.42 (2H, m), 1.15 (3H, d, J=2.86 Hz), 1.11 (3H, s), 0.76 (1H, dd, J=11.44, 9.68 Hz). MS (m+1)=571 HPLC Peak RT=3.35 minutes (Analytical Method A). Purity=92%.

Provenance & Evidence