Trifluoroacetic acid → 3-Fluoro-1-(2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidine-3-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a mixture of 3-fluoropiperidine-3-carbonitrile, TFA (55 mg, 0.227 mmol), and cesium carbonate (122 mg, 0.376 mmol) in 2-propanol (2 mL) and DMSO (0.5 mL) was added 3-(4-(oxiran-2-yl)phenyl)-5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazole, Preparation 28C (30 mg, 0.075 mmol). The reaction mixture was heated at 80° C. over a weekend. The reaction mixture was purified by HPLC. The purified product was lyophilized and then was dissolved in MeCN/6N HCl and heated at 50° C. overnight. The 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. Isolated fractions with correct mass were freeze-dried overnight to yield 6 mgs of 3-fluoro-1-(2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidine-3-carboxylic acid as a TFA salt. 1H NMR (400 MHz, MeOH-d3) δ ppm 8.14 (2H, d, J=7.91 Hz), 7.56-7.62 (4H, m), 7.44-7.56 (3H, m), 5.13-5.24 (1H, m), 3.86-4.28 (1H, m), 3.47-3.81 (2H, m), 3.25-3.41 (2H, m), 2.08-2.15 (3H, m), 1.87-2.02 (2H, m). MS (m+1)=547. HPLC Peak RT=3.32 minutes (Analytical Method A). Purity=98%.

Provenance & Evidence