The reaction of 3-bromomethyl-1,2-benzisoxazole (I) with sodium sulfite in hot methanol - water gives sodium 1,2-benzisoxazole-3-methanesulfonate (II), which by reaction with refluxing POCl3 is converted into 1,2-benzisoxazole-3-methanesufonyl chloride (III). Finally, this compound is treated with dry NH3 in ethyl acetate.

The reaction of 3-bromomethyl-1,2-benzisoxazole (I) with sodium sulfite in hot methanol - water gives sodium 1,2-benzisoxazole-3-methanesulfonate (II), which by reaction with refluxing POCl3 is converted into 1,2-benzisoxazole-3-methanesufonyl chloride (III). Finally, this compound is treated with dry NH3 in ethyl acetate.

The reaction of 4-hydroxy-H-1-benzopyran-2-one (I) with hydroxylamine by means of NaOEt in ethanol gives 2-(1,2-benzisoxazol-3-yl)acetic acid (II), which is sulfonated by means of H2SO4 and Ac2O in refluxing ethyl acetate, or ClSO3H in refluxing dichloromethane, to yield 1,2-benzisoxazol-3-ylmethylsulfonic acid (III). The reaction of (III) with refluxing POCl3 affords the sulfonyl chloride (IV), which is finally treated with ammonia in ethyl acetate to provide the target Zonisamide