A preparing method of 2,4-dichloro-5-sulfamoylbenzoic acid

Abstract

The invention relates to a preparing method of a medicine intermediate, and particularly relates to a preparing method of 2,4-dichloro-5-sulfamoylbenzoic acid. The method includes performing sulfurization by adopting 2,4-dichlorobenzoic acid and chlorosulfonic acid as initial raw materials, sodium sulfate as a catalyst and NMP as a solvent; centrifuging to obtain 2,4-dichloro-5-carboxybenzenesulfonyl chloride; subjecting the 2,4-dichloro-5-carboxybenzenesulfonyl chloride to ammoniation with ammonia water; acidifying; washing with water to obtain a crude product of the 2,4-dichloro-5-sulfamoylbenzoic acid; purifying the crude product with ethanol; and recrystallizing to obtain a 2,4-dichloro-5-sulfamoylbenzoic acid product with high quality. The method is less in process steps, easily available in raw materials, low in pollution, high in product purity and low in cost, and is a green synthesis route.

Description

technical field

[0001] The invention belongs to a preparation method of a pharmaceutical intermediate, in particular to a preparation method of 2,4-dichloro-5-sulfonamide benzoic acid. Background technique

[0002] 2,4-dichloro-5-sulfonamide benzoic acid, the English name Lasamide, is an important intermediate of furosemide. Furosemide, also known as furosemide and diuretic, is suitable for primary and secondary hypertension, especially for elderly patients with hypertension or complicated by heart failure. It is clinically used to treat peripheral edema caused by cardiac edema, renal edema, liver cirrhosis ascites, dysfunction or vascular disorder, and can promote the discharge of upper urinary tract stones. Its diuretic effect is rapid and powerful, and it is mostly used in severe cases where other diuretics are ineffective. There are following problems in the method for present traditional synthetic 2,4-dichloro-5-sulfonamide benzoic acid: 1. in the reaction process, du...

Examples

Embodiment 1

[0017] The preparation method of 2,4-dichloro-5-sulfonamide benzoic acid of the present invention comprises the following steps:

[0018] (1) Sulfonation: use 2,4-dichlorobenzoic acid and chlorosulfonic acid as raw materials, and sodium sulfate as a catalyst; first add N-methylpyrrolidone into the reaction kettle, then add 2,4-dichlorobenzoic acid and Sodium sulfate, heat the material to 145 ° C, after the material is completely dissolved, start to add chlorosulfonic acid dropwise, and keep warm for 5 hours after the dropwise addition;

[0019] (2) Centrifugation: cool down the reacted material in step (1) to room temperature, centrifuge the product, and recover the solvent to obtain the intermediate 2,4-dichloro-5-carboxybenzenesulfonyl chloride;

[0020] (3) Ammonification: Put the ammonia water into the ammoniation kettle, open the jacket of the ammoniation kettle, cool down with ice salt, wait until the temperature of the ammonia water in the kettle drops to 0°C, slowly ad...

technical field

[0001] The invention belongs to a preparation method of a pharmaceutical intermediate, in particular to a preparation method of 2,4-dichloro-5-sulfonamide benzoic acid. Background technique

[0002] 2,4-dichloro-5-sulfonamide benzoic acid, the English name Lasamide, is an important intermediate of furosemide. Furosemide, also known as furosemide and diuretic, is suitable for primary and secondary hypertension, especially for elderly patients with hypertension or complicated by heart failure. It is clinically used to treat peripheral edema caused by cardiac edema, renal edema, liver cirrhosis ascites, dysfunction or vascular disorder, and can promote the discharge of upper urinary tract stones. Its diuretic effect is rapid and powerful, and it is mostly used in severe cases where other diuretics are ineffective. There are following problems in the method for present traditional synthetic 2,4-dichloro-5-sulfonamide benzoic acid: 1. in the reaction process, du...

Examples

Embodiment 1

[0017] The preparation method of 2,4-dichloro-5-sulfonamide benzoic acid of the present invention comprises the following steps:

[0018] (1) Sulfonation: use 2,4-dichlorobenzoic acid and chlorosulfonic acid as raw materials, and sodium sulfate as a catalyst; first add N-methylpyrrolidone into the reaction kettle, then add 2,4-dichlorobenzoic acid and Sodium sulfate, heat the material to 145 ° C, after the material is completely dissolved, start to add chlorosulfonic acid dropwise, and keep warm for 5 hours after the dropwise addition;

[0019] (2) Centrifugation: cool down the reacted material in step (1) to room temperature, centrifuge the product, and recover the solvent to obtain the intermediate 2,4-dichloro-5-carboxybenzenesulfonyl chloride;

[0020] (3) Ammonification: Put the ammonia water into the ammoniation kettle, open the jacket of the ammoniation kettle, cool down with ice salt, wait until the temperature of the ammonia water in the kettle drops to 0°C, slowly ad...