HCID 66955253, compound → 3-Hydroxy-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-(4-(oxiran-2-yl)phenyl)-5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazole, Preparation 28C (30 mg, 0.075 mmol) in MeOH (3 mL) was added methyl 3-(trimethylsilyloxy)piperidine-3-carboxylate (100 mg, 0.432 mmol). The reaction mixture was heated at 80° C. for 2 days. The reaction mixture was concentrated in vacuo. The residue was treated with 6N HCl/MeCN at 50° 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. Isolated fractions with correct mass were freeze-dried overnight to yield 14 mg of 3-hydroxy-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 8.23 (2H, d, J=7.91 Hz), 7.69 (4H, t, J=7.91 Hz), 7.54-7.65 (3H, m), 5.21-5.32 (1H, m), 3.69-4.01 (1H, m), 3.51 (2H, d, J=12.30 Hz), 3.33-3.43 (1H, m), 3.07-3.27 (2H, m), 2.32 (1H, br. s.), 1.78-2.08 (3H, m). MS (m+1)=545. HPLC Peak RT=3.24 minutes (Analytical Method A). Purity=95%.

Provenance & Evidence