Technological method for preparing sulbactam by means of recycle hydrogen reduction

A process method and technology for circulating hydrogen, which are applied in the synthesis of sulbactam and the synthesis of pharmaceutical organic chemistry, can solve the problems of long operation time, difficult to meet requirements, and high equipment requirements, improve yield and quality, and reduce by-product generation. , mild conditions and friendly effect

Inactive Publication Date: 2014-12-17
GUANGZHOU UNIVERSITY
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Chinese patent (application number: 200510102131.1; publication number: CN1786002A) introduces a kind of intermittent hydrogen reduction process using palladium carbon as a catalyst. The strength is weak, resulting in low catalyst recovery rate and high production cost
The technology introduced by Song Zhimei and others in "Chinese Medicinal Chemistry" 2004 No. 6, Wang Zhengping in "Fine Chemical Raw Materials and Intermediates" 2005 No. 9, Qiu Fangli in "Chemical World" 2006 No. 2 and the current technology There are following deficiencies in the technology: 1. The existing technology mainly adopts zinc powder or magnesium powder as a reducing agent to carry out reduction debromination, and in the production process, the surface of the required zinc powder or magnesium powder is pickled and purified, and the existing technology is relatively complicated. Poor process stability and low product yield
2. Another fatal shortcoming of sulbactam prepared by reductive debromination using zinc powder or magnesium powder as a reducing agent in the prior art is that the product inevitably contains a trace amount of zinc or magnesium. When the product is tested for turbidity , it is difficult to meet the requirements of the Pharmacopoeia of the People's Republic of China (2010 edition)
3. The reductive debromination process takes a long time to operate, which increases the chance of by-product formation and affects the yield and quality of sulbactam
High requirements on equipment, complex process, not suitable for large-scale industrial production

Method used

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  • Technological method for preparing sulbactam by means of recycle hydrogen reduction

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Experimental program
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Embodiment 1

[0037] as attached figure 1 Shown, the liquid circulation system that adopts when the present invention is implemented is as follows:

[0038]The hydrogenation reactor mainly includes a reactor 8, a vacuum system, a hydrogen supply system, and a liquid circulation system; the vacuum system is connected to the reactor 8 through a vacuum pipeline 2, and the hydrogen supply system is connected to the reactor through a hydrogen supply pipeline 3. The tanks 8 are connected; the top of the reactor 8 is provided with a feeding port 5; the liquid circulation system sucks the liquid material in the reactor 8, and then sprays it out from the circulating medium jet nozzle 16 located at the top of the reactor 8.

[0039] The liquid circulation system includes a circulation pump 12, a volume flow meter 15 and a circulation medium jet nozzle 16 connected in series through pipelines; the circulation pump 12 is connected with the reaction liquid discharge port at the bottom of the reactor 8 t...

Embodiment 2

[0049] Dissolve 90g of dibromopenicillane sulfonic acid in 300mL of ethyl acetate, add it to a 1000mL magnetically stirred high-pressure hydrogenation reactor with a grid-type filter buffer plate at the bottom, and add 4g of Raney nickel catalyst with an average diameter of 20 mesh, and close the high-pressure still, use a vacuum pump to evacuate the high-pressure hydrogenation reactor to an absolute pressure of 90Pa, stop vacuuming, feed hydrogen into the hydrogenation reactor and keep the pressure of the reactor at 0.5MPa, open the hydrogenation reactor to circulate the ice salt water in the cooling medium jacket, Control the temperature in the hydrogenation reactor to 0°C. In the state of stirring, turn on the circulating pump, suck out the liquid phase reaction medium from the bottom of the reactor, inject it into the circulating medium jet nozzle on the top of the reactor, and the liquid phase medium with a certain pressure passes through the circulating medium jet nozzle ...

Embodiment 3

[0053] With 145g dibromopenicillane sulfonic acid, 300mL ethyl acetate, add respectively in the 1000mL magnetic stirring high-pressure hydrogenation reactor, utilize embodiment 2 to automatically filter and stay in the Raney nickel catalyst in the hydrogenation reactor, close the autoclave, and vacuum pump When the high-pressure hydrogenation reactor is evacuated to an absolute pressure of 100Pa, stop vacuuming, feed hydrogen into the hydrogenation reactor and keep the pressure of the reactor at 0.8MPa, and use the ice-salt water in the hydrogenation reactor to circulate the cooling medium jacket to adjust the temperature in the hydrogenation reactor is 3°C. Start the stirring and circulation pump to make the reaction medium realize extracorporeal circulation and enter the circulating medium jet nozzle on the top of the reactor. After circulating for 40 minutes, stop the stirring and circulation, and release the pressure of the hydrogenation reactor to normal pressure. Evapora...

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Abstract

The invention provides a technological method for preparing sulbactam by means of recycle hydrogen reduction, and belongs to the field of organic synthesis. In the reaction process of preparing the sulbactam by reduction and debromination of dibromo sulbactam, raney nickel is taken as catalyst, the dibromo sulbactam is subjected to reduction and debromination under the pressure of 0.5-0.8MPa hydrogen in a circulating liquid phase jet-flowing way, the reaction product is absorbed by activated carbon to become purified, the purity of the manufactured sulbactam is more than 98%, and the total recovery is more than 90%. Compared with the currently used synthesis method, the technological method has the remarkable technical advantages of high efficiency for the technological process, short time for reduction and debromination, high product recovery, stable quality of the product, low synthesis cost, and wide sources of raw materials. The technological method can be widely applied to the preparation of sulbactam.

Description

technical field [0001] The invention relates to the field of organic synthesis, in particular to a synthesis method of medical organic chemistry, in particular to a synthesis method of sulbactam. Background technique [0002] The combined use of sulbactam and broad-spectrum antibiotics penicillin or cephalosporin can effectively stabilize the β-lactam ring in the structure of penicillin or cephalosporin, and improve the effective antibacterial time of penicillin or cephalosporin in the organism, thereby achieving a small Dose high effect purpose. In the preparation process of sulbactam, 6-APA (6-aminopenicillinic acid) is usually used as raw material, and in the presence of hydrobromic acid, bromine is used as a brominating agent to carry out double bromination reaction, and then treated with permanganese The β-lactamase inhibitor, sulbactam, was obtained through a three-step reaction through potassium acid potassium oxidation and debromination of the reducing agent. [00...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D499/86C07D499/04
Inventor 王正平吴旭刘莹
Owner GUANGZHOU UNIVERSITY
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