3-Phenyl-4-(trifluoromethyl)isoxazole-5-carbonyl fluoride, Int-I-G (214 mg, 0.78 mmol) was dissolved in acetonitrile (5.00 mL). DIEA (0.272 mL, 1.555 mmol) and (S)-ethyl-1-((S)-2-hydroxy-2-(4-((Z)-N′-hydroxycarbamimidoyl) phenyl)ethyl)-piperidine-3-carboxylate (261 mg, 0.778 mmol) were added. The reaction mixture was stirred for 2 hours, then 1M TBAF in THF (0.778 mL, 0.778 mmol) was added. The reaction mixture was stirred overnight at room temperature. The reaction mixture was filtered and purified by HPLC in three batches. HPLC conditions: PHENOMENEX® Luna C18 5 micron column (250×30mm); 25-100% CH3CN/water (0.1% TFA); 25 minute gradient; 30 mL/min. Isolated fractions with correct mass were partitioned between EtOAc and saturated NaHCO3 with back extracting aqueous layer once. The organic layer was dried with MgSO4, filtered, and concentrated to give 155mg of (S)-ethyl 1-((S)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidine-3-carboxylate. 1H NMR (400 MHz, MeOH-d3) δ ppm 8.04 (2H, d, J=8.13 Hz), 7.55-7.60 (2H, m), 7.41-7.54 (5H, m), 4.81 (1H, ddd, J=8.35, 4.06, 3.84 Hz), 3.96-4.10 (2H, m), 2.82-3.08 (1H, m), 2.67-2.82 (1H, m, 2.36-2.61 (3H, m), 2.08-2.33 (2H, m), 1.73-1.87 (1H, m, J=8.54, 8.54, 4.45, 4.17 Hz), 1.32-1.70 (3H, m), 1.09-1.19 (3H, m). MS (m+1)=557. HPLC Peak RT=3.36 minutes. Purity=99%.
