Method for sulfonation of 1,2-benzisoxazole-3-acetic acid

1. A one-pot method of manufacturing 1,2-benzisoxazole-3-methanesulfonamide, which comprises:

(a) providing a first mixture of 1,2-benzisoxazole-3-methanesulfonic acid and toluene by a method, which comprises: adding chlorosulfonic acid, optionally mixed with an inert solvent, to a mixture of 1,2-benzisoxazole-3-acetic acid, toluene and a Lewis base selected from the group consisting of a C 2-5 saturated aliphatic mono-carboxylic acid C 1-4 alkyl ester, a benzoic acid C 1-4 alkyl ester, a C 1-4 alkyl cyanide and benzonitrile; and heating the mixture;

(b) adding aqueous alkali metal hydroxide solution to the first mixture and removing water by azeotropic distillation to give a second mixture;

(c) adding phosphorous oxychloride to the second mixture and reacting the mixture to give a third mixture;

(d) adding ammonia to the third mixture and reacting the mixture to give a fourth mixture containing 1,2-benzisoxazole-3-methanesulfonamide; and

(e) isolating the 1,2-benzisoxazole-3-methanesulfonamide.

2. The method according to claim 1 , wherein the Lewis base is a C 2-5 saturated aliphatic mono-carboxylic acid C 1-4 alkyl ester.

3. The method according to claim 1 , wherein the Lewis base is a C 2-5 saturated aliphatic mono-carboxylic acid ethyl ester.

4. The method according to claim 1 , wherein the Lewis base is ethyl acetate or isobutyric acid ethyl ester.

5. The method according to claim 1 , wherein the inert solvent is dichloromethane, chloroform, or 1,2-dichloroethane.

6. The method according to claim 1 , wherein the aqueous alkali metal hydroxide solution is aqueous sodium hydroxide solution.

7. The method according to claim 1 , wherein the ammonia is ammonia gas.

8. The method according to claim 1 , wherein a tertiary amine is added to the second mixture in step (c).