2-Dicyclohexylphosphino-2',6'-diisopropoxy-1,1'-biphenyl (580 mg, 1.25 mmol) and tris(dibenzylideneacetone)dipalladium (760 mg, 0.83 mmol) were added to 5-(1-(3-bromobenzyl)-5-methyl-1H-1,2,4-triazol-3-yl)-3-(4-(trifluoromethoxy)phenyl)-1,2 ,4-oxadiazole (2.00 g, 4.16 mmol), 4-methanesulfonylpiperidine (1.02 g, 6.24 mmol) and sodium tert-butanolate (800 mg, 8.33 mmol) in a solution of toluene (80 mL). The reaction mixture was degassed with argon for 3 minutes and then heated to 140 °C under argon atmosphere and kept for 18 hours. Upon completion of the reaction, the mixture was cooled to room temperature, diluted with ethyl acetate (100 mL), filtered through a pad of diatomaceous earth and washed with ethyl acetate (100 mL). The filtrate was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:1 followed by pure ethyl acetate) to give the crude product. The crude product was treated with ethyl acetate and ether (1:9, 30 mL, v/v), and the resulting suspension was stirred at room temperature for 30 min and filtered to afford 5-(5-methyl-1-(3-(4-(methylsulfonyl)piperidin-1-yl)benzyl)-1H-1 ,2,4-triazol-3- yl)-3-(4-(trifluoromethoxy)phenyl)-1 ,2,4-oxadiazole as a white solid (905 mg, 39% yield). The product was characterized by 1H NMR, 13C NMR, 19F NMR and HRMS.
