A 2 dram reaction vial containing a stir bar was charged with 4,5-diphenylisoxazole-3-carboxylic acid (17-B, 48.6 mg, 0.183 mmol), EDC (43.9 mg, 0.229 mmol), HOBT (35.1 mg, 0.229 mmol), and dimethylformamide (1 mL). The vial was flushed with dry nitrogen, sealed, and the reaction was stirred at room temperature for 30 minutes. N′-Hydroxy-4-methyl-2-(trifluoromethyl)benzimidamide (40.0 mg, 0.183 mmol) was introduced. The vial was flushed with dry nitrogen, sealed, stirred at room temperature for 30 minutes, and then placed on a reactor block set to 60° C. overnight. Water was added dropwise (−0.5 mL) until the solution remained cloudy, and then the reaction was cooled to room temperature. Additional water (5 mL) was added after cooling, and the reaction was placed in a sonicator bath for 60 min. A gummy solid formed on the side of the flask and stir bar. The aqueous solution was decanted and the residue washed with water and then partially dried under a stream of air. The gummy solid was dissolved in methanol (1-2 mL), transferred, and evaporated to dryness to give a pale yellow solid The pale yellow solid was purified by flash chromatography (12 g Isco silica gel). Elution with dichloromethane afforded the major product. The product containing fractions were evaporated to afford 5-(4,5-diphenylisoxazol-3-yl)-3-(4-methyl-2-(trifluoromethyl)phenyl)-1,2,4-oxadiazole (24 mg) MS M+1=448.1.
