To a mixture of 3-phenyl-4-(trifluoromethyl)isoxazole-5-carboxylic acid (70.8 mg, 0.275 mmol) and oxalyl chloride (0.048 mL, 0.550 mmol) in DCM (5 mL) was added DMF (3 drops) at 25° C. The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated in vacuo and dried. The residue was dissolved in acetonitrile (5.00 mL). Next, DIEA (0.048 mL, 0.275 mmol) and (3S)-ethyl 1-(1-hydroxy-1-(4-((Z)—N′-hydroxycarbamimidoyl)phenyl)-2-methylpropan-2-yl)piperidine-3-carboxylate (100 mg, 0.275 mmol) were added. The reaction mixture was stirred at 25° C. After stirring overnight, the reaction mixture showed a significant amount of coupled but uncyclized material. Next, 1M TBAF in THF (0.275 mL, 0.275 mmol) was added and reaction mixture was stirred for another 48 hrs. 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. The residue was treated with 6N HCl/dioxane (1:1) 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 and freeze-dried overnight. Recovered 32 mg of (3S)-1-(1-hydroxy-2-methyl-1-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)propan-2-yl)piperidine-3-carboxylic acid, TFA. MS (m+1)=547. HPLC Peak RT=1.90 minutes (Analytical Method B). Purity=92%.
