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Synthetic method of bumetanide

A synthetic method and amino technology, applied in the preparation of sulfonamides, organic chemistry, etc., can solve the problems of unsuitability for industrial production, expensive deuterated reagents, complicated reaction process, etc., and achieve short reaction time, simple operation, and excellent reaction process. simple effect

Active Publication Date: 2017-05-31
枣庄市润安制药新材料有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, this method requires a two-step reaction, the reaction process is complicated, and the steps are cumbersome; at the same time, the reaction needs to use palladium carbon catalyst, nitrogen protection and hydrogen pressurization, which has high requirements for the reaction environment and equipment.
[0007] Patent WO2012154728A1 also discloses the synthesis method of bumetanide, which is to use 3-amino-4-phenoxy-5-sulfonamide benzoic acid and deuterated n-butyraldehyde as raw materials, and then deuterated hydrogen / Pd / C or NaCNBD 3 The corresponding product is prepared by the reaction, but the above method also requires a two-step reaction, the reaction process is complicated, the steps are cumbersome, and the deuterium reagent used is expensive, which is not suitable for industrial production

Method used

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  • Synthetic method of bumetanide

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Experimental program
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Effect test

Embodiment 1

[0022] The 3-amino-4-phenoxy group-5-sulfonamide benzoic acid of 0.1mol is joined in the reaction flask, then add 500ml n-butanol, stir at room temperature, then add 10mmol iron trichloride catalyst in the reaction flask, React for 6 hours. After the reaction is over, stop stirring, evaporate most of the n-butanol from the reaction solution, add 200ml of 2M sodium hydroxide solution and 100ml of ethanol, heat and reflux for 30 minutes, then add concentrated hydrochloric acid to adjust the pH to 8-8.2, and cool , stand still, suction filtration, after suction filtration, add water to the filter cake and heat to dissolve, add a small amount of activated carbon to decolorize, heat filter and cool to precipitate sodium salt, add 300ml water to heat to dissolve after suction filtration, then add concentrated hydrochloric acid to acidify to pH2- 3. Cooling, suction filtration, washing with water and drying to obtain pure bumetanide with a yield of 64.5% and a purity of 99.6%.

Embodiment 2

[0024] The 3-amino-4-phenoxy group-5-sulfonamide benzoic acid of 0.1mol is joined in the reaction flask, then add 500ml n-butanol, stir at room temperature, then add 10mmol tin tetrachloride catalyst in the reaction flask, React for 6 hours. After the reaction is over, stop stirring, evaporate most of the n-butanol from the reaction solution, add 200ml of 2M sodium hydroxide solution and 100ml of ethanol, heat and reflux for 30 minutes, then add concentrated hydrochloric acid to adjust the pH to 8-8.2, and cool , stand still, suction filtration, after suction filtration, add water to the filter cake and heat to dissolve, add a small amount of activated carbon to decolorize, heat filter and cool to precipitate sodium salt, add 300ml water to heat to dissolve after suction filtration, then add concentrated hydrochloric acid to acidify to pH2- 3. Cooling, suction filtration, washing with water and drying to obtain pure bumetanide with a yield of 86.2% and a purity of 99.4%.

Embodiment 3

[0026] Add 0.1mol of 3-amino-4-phenoxy-5-sulfonamidobenzoic acid to the reaction flask, then add 500ml of n-butanol, stir at room temperature, then add 10mmol of boron trifluoride ether catalyst to the reaction flask , reacted for 6 hours, after the reaction was finished, stop stirring, evaporate most of the n-butanol from the reaction solution, add 200ml of 2M sodium hydroxide solution and 100ml of ethanol and heat to reflux for 30 minutes, then add concentrated hydrochloric acid to adjust the pH to 8-8.2, Cool, stand still, and suction filter. After suction filtration, add water to the filter cake and heat to dissolve. After adding a small amount of activated carbon for decolorization, heat filter and cool to precipitate sodium salt. After suction filtration, add 300ml of water to heat and dissolve, then add concentrated hydrochloric acid to acidify to pH2 -3, cooling, suction filtration, washing and drying to obtain pure bumetanide with a yield of 76.8% and a purity of 99.5%...

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Abstract

The invention provides a synthetic method of bumetanide. The synthetic method comprises the following specific steps: 3-amino-4-phenoxy-5- sulfamoylbenzoic acid and n-butyl alcohol are added to a reactor and stirred at room temperature, a Lewis acid catalyst is added, a reaction is performed for 2-10 h, and pure bumetanide is obtained through post-processing after the reaction. The method is short in reaction step, short in reaction time and high in efficiency, the product yield and purity are higher, reaction conditions are mild, equipment corrosion is avoided, and industrial production is facilitated.

Description

technical field [0001] The invention relates to a method for synthesizing medicine, in particular to a method for synthesizing bumetanide. Background technique [0002] Bumetanide (bumetanide) is commonly known as diuretic amine, and its chemical name is 3-n-butylamino-4-phenoxy-5-sulfamylbenzoic acid (3-n-butylamino-4-phenoxy-5-sulfamylbenzoic acid). Metanide is a non-mercury non-benzothiazide high-efficiency, low-toxic new diuretic; its diuretic effect is 40 times higher than that of furosemide; it is used for the treatment of hepatitis B edema, and the oral dose is 1-2 mg / d, yes 1 / 40 of furosemide. [0003] There are multiple methods for synthesizing bumetanide in the prior art, such as synthesizing by the following formula: [0004] [0005] The catalyzer that this method adopts is sulfuric acid, because sulfuric acid has strong corrosiveness, therefore needs to carry out in the complex dehydration equipment, and the time of this reaction is long, post-treatment is ...

Claims

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Application Information

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IPC IPC(8): C07C303/40C07C311/39
CPCC07C303/40C07C311/39
Inventor 张奉志
Owner 枣庄市润安制药新材料有限公司
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