Method for preparing candesartan through continuous flow of microreactor

A technology of microreactor and candesartan, which is applied in the field of continuous flow preparation of candesartan by microreactor, can solve the problems of high production cost and long reaction time, and reduce the generation of by-products and solvents The effect of usage amount and shortening reaction time

Pending Publication Date: 2022-03-08
ZHEJIANG YONGNING PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0008] Aiming at the problems of explosion risk, environmental protection risk, long reaction time and high production cost in the traditional preparation process, the present invention provides a method for preparing candesartan by continuous flow in a microreactor, which is safe and easy to operate , economical and environmentally friendly, with high yield and good product quality, more suitable for industrial production

Method used

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  • Method for preparing candesartan through continuous flow of microreactor
  • Method for preparing candesartan through continuous flow of microreactor
  • Method for preparing candesartan through continuous flow of microreactor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] A microreactor comprising unit A, unit B and unit C for continuous flow reaction is selected for the following reactions.

[0052] Configure 365g / L sodium azide aqueous solution in a 1L three-necked flask, flow into unit A of the microreactor at a flow rate of 75ml / min, and simultaneously pump tri-n-butyltin chloride into the microreactor at a flow rate of 110ml / min Unit A of the microreactor, the residence time of the reaction is 34 seconds, and the reaction temperature is controlled at 30°C; after the reaction liquid flows from unit A of the microreactor into unit B, the prepared 270g / L xylene solution dissolved in C6 Simultaneously pump into unit B of the microreactor at a flow rate of 260 ml / min, the residence time of the reaction unit is 72 seconds, and the reaction temperature is controlled at 175°C.

[0053]After the reaction liquid flows into the C unit from the B unit, the sodium hydroxide solution of 105g / L is pumped into the C unit of the microreactor at a fl...

Embodiment 2～6

[0055] According to the corresponding addition amount of raw materials and reaction conditions in Table 1, referring to the preparation process in Example 1, the preparation of candesartan in Examples 2-6 was carried out.

[0056] Raw material addition and reaction conditions of different embodiments of table 1

[0057]

[0058]

[0059] Known by embodiment 1~6, the purity of the product of production is all more than 98%, and product yield is all more than 87%, illustrates that adopting the method of the present invention to prepare candesartan can effectively improve the yield and purity of product, reduce Production cost; and the reaction time is short, the operation steps are simple, continuous and automatic production can be realized, and the safety is high.

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Abstract

The invention provides a method for preparing candesartan through continuous flow of a microreactor. According to the method, candesartan is prepared through continuous flow of a microreactor, and the microreactor comprises a unit A, a unit B and a unit C which are used for carrying out continuous flow reaction; the method comprises the following steps: mixing a sodium azide solution with tri-n-butyltin chloride in a unit A for reaction to obtain a reaction solution I containing tri-n-butyltin azide; the reaction solution I and the C6 solution enter a unit B at the same time for reaction to obtain a reaction solution II containing an intermediate C7, the reaction solution II and a sodium hydroxide solution enter a unit C at the same time for hydrolysis reaction, and candesartan is obtained through post-treatment. According to the method, the operation steps are greatly simplified, the reaction time is shortened, the dosage of various solvents is reduced, the production cost is reduced, the production safety is improved, continuous and automatic production can be achieved, the obtained product is high in purity and yield, and the method is suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a method for preparing candesartan by using a microreactor continuous flow. Background technique [0002] Candesartan is an antihypertensive drug whose structural formula is shown in the following formula. [0003] [0004] Candesartan is a selective angiotensin Ⅱ receptor (AT1) antagonist, which antagonizes the vasoconstriction of angiotensin Ⅱ by binding to vascular smooth muscle AT1 receptor, thereby reducing peripheral vascular resistance. Antihypertensive drug with good market prospect. [0005] The patent literature with the application number CN91102569.3 discloses the structural formula of candesartan and its synthetic route, and the candesartan cyclic compound C6 (1-[(2'-cyanobiphenyl-4-yl)methyl] -2-ethoxybenzimidazole-7-ethyl carboxylate) as raw material, under the action of trimethyltin azide, the cyano group on the 2' position is converted ...

Claims

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Application Information

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IPC IPC(8): C07D403/10
CPCC07D403/10
Inventor 叶天健陈鑫郑豪叶继华袁尤挺
Owner ZHEJIANG YONGNING PHARMA
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