455280-00-9

546-88-3

179897-89-3

455280-00-9

3-Amino-5-bromobenzo[d]isoxazoles were synthesized from acetohydroxamic acid and 2-fluoro-5-bromobenzonitrile according to a modified literature method (Palermo, M.G., Tetrahedron Lett, 37: 2885, 1996). The procedure was as follows: in a 50 mL single-neck flask equipped with a magnetic stirrer, N-hydroxyacetamide (2.63 g, 35.0 mmol) and N,N-dimethylformamide (DMF, 100 mL) were added. Subsequently, potassium tert-butoxide (KOtBu, 3.93 g, 35.0 mmol) was added all at once. The reaction system was heated to 300 °C and stirred for 1 h. 5-Bromo-2-fluorobenzonitrile (7 g, 35.0 mmol) was added. Stirring of the reaction mixture was continued overnight. Another portion of potassium tert-butoxide (1.96 g, 17.5 mmol) was added and the solution was stirred again overnight. After completion of the reaction, the mixture was poured into saturated saline and dichloromethane (CH2Cl2) to separate the organic and aqueous phases. The organic phase was dried with anhydrous sodium sulfate (Na2SO4) and concentrated under reduced pressure. The residue was purified by fast column chromatography (BIOTAGE system with 0 to 40% ethyl acetate/hexane gradient elution) to afford the target product 3-amino-5-bromobenzo[d]isoxazole (4.59 g, 62% yield) as a colorless solid. The product was confirmed by 1H NMR (500 MHz, DMSO-d6) and LCMS characterization.1H NMR data: δ 8.09 (d, J = 1.8 Hz, 1H), 7.65 (dd, J = 2.1, 8.9 Hz, 1H), 7.45 (d, J = 8.9 Hz, 1H), 6.49 (s, 2H).The LCMS result was in agreement with the calculated value ( C7H5BrN2O) were consistent.