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 of preparing a BOS-Na Form IV, comprising the steps of: 1) preparing a slurry of BOS-Na in the presence of an organic solvent selected from the group consisting of ethanol, isopropanolol and methanol; 2) heating the slurry to form a gel; and 3) evaporating the organic solvent to obtain the BOS-Na Form IV.  
     
     
         2 . The process of  claim 1 , wherein the slurry is heated at a reflux temperature of the organic solvent.  
     
     
         3 . The process of  claim 1 , wherein the organic solvent is ethanol.  
     
     
         4 . The process of  claim 3 , wherein the ethanol is an absolute ethanol.