Process for the prepartion of 1,2-benzisoxazole-3-acetic acid

Abstract

The present invention provides a process for preparing 1,2-benzisoxazole-3-acetic acid, comprising the step of reacting 4-hydroxy-coumarin with hydroxyl-amine in the presence of a base. The present invention further provides a process for preparing a salt of benzisoxazole methane sulfonic acid, comprising the steps of 1) sulfonating 1,2-benzisoxazole-3-acetic acid using chlorosulfonic acid in a solvent mixture comprising methylene chloride and sodium hydroxide; and 2) isolating the salt of benzisoxazole methane sulfonic acid.

What is claimed is:  
     
         1 . A process for preparing 1,2-benzisoxazole-3-acetic acid, comprising the step of reacting 4-hydroxy-coumarin with hydroxyl-amine in the presence of a base.  
     
     
         2 . The process according to  claim 1 , wherein the base is selected from the group consisting of carbonate salts, aqueous ammonia, and organic bases.  
     
     
         3 . The process according to  claim 2 , wherein the carbonate salt is selected from the group consisting of sodium carbonate and potassium carbonate  
     
     
         4 . The process according to  claim 2 , wherein the organic base is an amine.  
     
     
         5 . The process according to  claim 4 , wherein the amine is selected from the group consisting of triethyl-amine, tributyl-amine, and diethyl-amine.  
     
     
         6 . The process according to  claim 1 , wherein the process is performed in the presence of an alcohol.  
     
     
         7 . The process according to  claim 6 , wherein the alcohol is a lower alcohol.  
     
     
         8 . The process according to  claim 7 , wherein the lower alcohol is selected from the group consisting of ethanol, methanol, n-butanol, iso-propyl-alcohol, isobutanol, amyl-alcohol, and iso-amyl alcohol.  
     
     
         9 . The process according to  claim 6 , wherein the process is performed at a temperature between room temperature and boiling point of the alcohol.  
     
     
         10 . The process according to  claim 9 , wherein the process is performed at a temperature between about 40° C. and about 60° C.  
     
     
         11 . A process of preparing a salt of benzisoxazole methane sulfonic acid comprising the steps of: 1) sulfonating 1,2-benzisoxazole-3-acetic acid using chlorosulfonic acid and dioxane in a solvent mixture comprising methylene chloride and sodium hydroxide; and 2) isolating the salt of benzisoxazole methane sulfonic acid.  
     
     
         12 . The process according to  claim 11 , wherein the isolating step is performed by evaporating the solvent mixture after the sulfonating step.  
     
     
         13 . The process according to  claim 11 , wherein the isolating step is performed by salting-out with sodium chloride.  
     
     
         14 . The process according to  13 , further comprising the step of cooling after the step of salting-out.  
     
     
         15 . The process according to  claim 11 , wherein the salt of benzisoxazole methane sulfonic acid is selected from the group consisting of sodium, calcium, and barium.  
     
     
         16 . The process according to  claim 11 , wherein the preparation of benzisoxazole methane sulfonic acid is performed at a temperature of about 40° C. and for a time of about 4 hours.  
     
     
         17 . The process according to  claim 11 , wherein the preparation of benzisoxazole methane sulfonic acid is performed at a temperature of about 40° C. and a time of about 5 hours.  
     
     
         18 . The process according to  claim 11 , wherein the preparation of benzisoxazole methane sulfonic acid is performed at a temperature of about 40° C. and a time of about 3 hours.  
     
     
         19 . The process according to  claim 11 , wherein the preparation of benzisoxazole methane sulfonic acid is performed at a temperature of about 55° C. and a time of about 3.5 hours.  
     
     
         20 . The process according to  claim 1 , wherein the 1,2-benzisoxazole-3-acetic acid is thereafter converted to 1,2-benzisoxazole-3-methane sulfonamide.  
     
     
         21 . The process according to  claim 11 , wherein the benzisoxazole methane sulfonic acid is thereafter converted to 1,2-benzisoxazole-3-methane sulfonamide.  
     
     
         22 . 1,2-benzisoxazole-3-methane sulfonamide prepared in accordance with the process of  claim 1 .  
     
     
         23 . 1,2-benzisoxazole-3-methane sulfonamide prepared in accordance with the process of  claim 11.