Diisopropylethylamine → (2-Fluoro-4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)methanol

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Reaction Steps

A heterogeneous mixture of 3-phenyl-4-(trifluoromethyl)isoxazole-5-carbonyl fluoride (1-E, 0.973 g, 3.75 mmol), 3-fluoro-N′-hydroxy-4-(hydroxymethyl)benzimidamide (0.691 g, 3.75 mmol), and Hunig's Base (0.852 mL, 4.88 mmol) in acetonitrile (7 mL) was stirred at room temperature over the weekend. The reaction mixture was diluted with dichloromethane, washed with a saturated aqueous solution of sodium bicarbonate, and dried over anhydrous sodium sulfate. The dichloromethane was removed under reduced pressure to give an orange oily residue which was purified by flash silica gel chromatography using a 20% mixture of ethyl acetate in hexane to give (2-fluoro-4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)methanol (0.762 g, 1.88 mmol, 50% yield) as a pale yellow solid. The compound had an HPLC ret. time=3.33 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=406.1.

Provenance & Evidence