To a mixture of 3-(3-(pyridin-2-yl)-4-(trifluoromethyl)isoxazol-5-yl)-7-vinyl-4,5-dihydronaphtho[1,2-c]isoxazole (Preparation 63F, 0.098 g, 0.239 mmol) and a 50% aqueous solution of NMO (0.050 mL, 0.239 mmol) at room temperature was added a 4% aqueous solution of osmium tetroxide (0.075 mL, 9.58 μmol). The reaction mixture was stirred at room temperature over the weekend. The intermediate diol had an HPLC ret. time=2.66 min and an LCMS M+1=443.8. Sodium periodate (0.077 g, 0.359 mmol) was added to the homogeneous mixture followed by water (0.15 mL), and the reaction was stirred for 60 min. at room temperature. Concentration under reduced pressure afforded a tan solid residue that was then diluted with ethyl acetate (40 mL), washed with the water (10 mL), and washed with brine (10 mL). The organic layer was collected, and the aqueous layer was washed with ethyl acetate (40 mL). The combined organic layers were dried over anhydrous sodium sulfate. Concentration under reduced pressure afforded 3-(3-(pyridin-2-yl)-4-(trifluoromethyl)isoxazol-5-yl)-4,5-dihydronaphtho[1,2-c]isoxazole-7-carbaldehyde (0.096 g, 0.233 mmol, 97% yield) as a pale yellow solid. The product had an HPLC ret. time=3.00 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. LC/MS M+1=411.9.
