Novel sulfonation method for zonisamide intermediate in zonisamide synthesis and their novel crystal forms

Abstract

The present invention relates to a novel sulfonation of an intermediate of zonisamide. The sulfonation processes using chlorosulfonic acid as well as acetic anhydride and sulfuric acid in an organic solvent are disclosed. Crystalline forms of benzisoxazole methane sulfonic acid (BOS-H) and its salts (BOS-Na, BOS-Ca, and BOS-Ba) and their novel preparation processes are disclosed.

1 . A process for preparing 1,2-benzisoxazole-3-methane sulfonamide, comprising 
 a) preparing a slurry of BOS-Na in the presence of an organic solvent selected from the group consisting of ethanol, isopropanol and methanol;    b) heating the slurry to form a gel;    c) evaporating the organic solvent to obtain the BOS-Na Form IV; and    d) converting the BOS-Na Form IV to 1,2-benzisoxazole-3-methane sulfonamide.