General procedure for the synthesis of 1,2-benzisoxazol-3-amine from 2-fluorobenzonitrile:
(1) Synthesis of 1,2-benzisoxazol-3-amine: potassium tert-butoxide (14.9 g, 133 mmol) was added to a solution of N,N-dimethylformamide (150 ml) containing acetohydroxamic acid (10.0 g, 133 mmol), and stirred for 30 min at room temperature. Subsequently 2-fluorobenzonitrile (18.0 g, 133 mmol) was added and the reaction continued to be stirred at room temperature for 5 hours. After completion of the reaction, the mixture was poured into water and extracted with ethyl acetate. The organic phases were combined, washed with water and dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure and the residue was recrystallized from hexane to give 4.80 g (27.0% yield) of the target product 1,2-benzisoxazol-3-amine as a solid. The product was characterized by 1H-NMR (CDCl3): δ 4.43 (2H, br s), 7.23-7.28 (1H, m), 7.43 (1H, d, J = 9.3Hz), 7.50-7.56 (2H, m).
