6-hydroxybenzo[d]isothiazole-3-carboxylic acid synthesis

Yield:677304-64-2 48% ，932702-33-5 37%

Reaction Conditions:

Stage #1: ethyl 6-methoxy-benzo[d]isothiazole-3-carboxylatewith boron tribromide in dichloromethane at 0 - 20; for 16 h;
Stage #2: with sodium hydroxide;water in dichloromethane at 0; for 0.333333 h;
Stage #3: with hydrogenchloride;water

Steps:

26

Procedure 26 Procedure 26 provides a preparation of 6-hydroxybenzisothiazole-3-carboxylic acid and the ester from the corresponding anisole. A 1.0 M solution of boron tribromide in methylene chloride (20.00 mL) was added dropwise to a 0° C. solution of ethyl 6-methoxy-1,2-benzisothiazole-3-carboxylate (12.6 mmol) in methylene chloride (30.0 mL). The reaction mixture was allowed to warm to rt and was maintained for 16 h. The reaction mixture was poured into 100 mL of ice cold 2 N sodium hydroxide and the mixture was stirred vigorously for 20 min. The precipitated solids were removed by filtration and the eluent was washed with ethyl acetate (2×50 mL). The aqueous layer was neutralized with 6 N hydrochloric acid and the precipitated tan solid was collected by filtration to give a mixture of the methoxy (?48% yield) and hydroxy acids (?37% yield).

References:

US2007/78147,2007,A1 Location in patent:Page/Page column 75