To a magnetically stirred solution of 4-phenylbicyclo[2.2.2]octane-1-carboxylic acid (8-A) (70 mg, 0.30 mmol) in methylene chloride (1 mL) at room temperature was added 2 M oxalyl chloride in methylene chloride (0.61 mL, 1.22 mmol). Two drops of catalytic DMF were added to catalyze the reaction. The reaction was stirred for 30 min and solvent and reagent removed in vacuo. Methylene chloride (1 mL) was added to the residue, followed by 4-(benzyloxy)-2-(trifluoromethyl)benzoic hydrazide (8-B) (141 mg, 0.46 mmol) and triethylamine (0.07 mL, 0.46 mmol). The reaction was stirred at room temperature overnight to afford intermediate 8-C, N′-[4-(benzyloxy)-2-(trifluoromethyl)benzoyl]-4-phenylbicyclo[2.2.2]octane-1-carbohydrazide, which was not isolated. To the crude product (8-C) were then added 2-chloro-1,3-dimethylimidazolinium chloride (257 mg, 1.52 mmol), more triethylamine (0.42 mL, 3.04 mmol), and methylene chloride (2 mL). The reaction was stirred at room temperature for 4 h. The reaction mixture was then diluted with methylene chloride (30 mL) and washed with water (30 mL) two times and with brine (30 mL) once. The combined aqueous layers were extracted with methylene chloride (25 mL) once. The combined organic layers were dried (MgSO4) and the solvent removed in vacuo. The residue was chromatographed on silica with 10% ethyl acetate in hexanes as eluant to give 2-[4-(benzyloxy)-2-(trifluoromethyl)pheny ]-5-(4-phenylbicyclo[2.2.2]oct-1-yl)-1,3,4-oxadiazole (8-D). MS: m/z 505 (M+1).
