Phosphorus tribromide → 3-(4-(Bromomethyl)-3-fluorophenyl)-5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazole

Participants

Reaction Steps

To a solution of (2-fluoro-4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)methanol (1.95 mL, 0.740 mmol) in dichloromethane (8 mL) at 0° C. was added phosphorus tribromide (1.0M in dichloromethane) (0.740 mL, 0.740 mmol). After 5 minutes, the ice bath was removed, and the reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with dichloromethane, washed with a saturated aqueous solution of sodium bicarbonate, washed with brine, and dried over anhydrous sodium sulfate. The residue was triturated with methanol with sonication, filtered, and washed with methanol. Analysis of the white solid by HPLC and LCMS indicated that there was no significant amount of the desired product present. The filtrate was concentrated under reduced pressure, and the compound was loaded with a minimum amount of dichloromethane on a fritted funnel containing a layer of CELITE® topped with a layer of silica gel. The plug column was eluted with dichloromethane to give 3-(4-(bromomethyl)-3-fluorophenyl)-5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazole (0.173 g, 0.370 mmol, 50% yield) as a white solid. The compound had an HPLC ret. time=3.72 min.−Column: CHROMOLITH® SpeedROD 4.6×50 mm (4 min.); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA. MS M+1=468.0 and 470.0.

Provenance & Evidence