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Synthetic process of canagliflozin

A synthesis process and process technology, applied in the field of new synthesis of canagliflozin, can solve the problems of harsh process conditions, high cost, low total yield, etc. Effect

Active Publication Date: 2016-08-03
HAIMEN RUIYI MEDICAL TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The existing synthetic routes reported in the literature have harsh process conditions, such as high-temperature thermal filtration, high requirements for production equipment, and high industrialization costs; due to the long preparation route, the yield of each step is low, resulting in low overall yield and environmental pollution. Large pollution, not conducive to industrial production

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] The new synthesis process of canagliflozin comprises the following steps:

[0033] a. With 2-methylbenzoic acid as the starting material, use catalyst molecular sieve to support iron oxide, react with iodic acid and iodine with a molar multiple of 0.5 to generate intermediate-5-iodo-2-methylbenzoic acid, post-treatment process After adopting the method of cold filtration after cooling down, the mother liquor is applied mechanically, specifically as follows: the reaction temperature is reduced to 20 degrees Celsius, and a large amount of solids are precipitated. At this temperature, the product mixed with the catalyst is filtered. After dissolving the cake with ethyl acrylate, filter at room temperature, filter out the catalyst and apply it mechanically for 5 times next time. After precipitation of the filtrate, the crude product is recrystallized with 2.5 times the weight of ethyl acrylate to obtain a white product with a yield of 88 %above;

[0034] B, or take 2-methy...

Embodiment 2

[0040] The new synthesis process of canagliflozin comprises the following steps:

[0041] a. With 2-methylbenzoic acid as the starting material, use the catalyst molecular sieve to support iron oxide, react with iodic acid and iodine with a molar multiple of 0.7 to generate intermediate-5-iodo-2-methylbenzoic acid, post-treatment process Adopt cold filtration after cooling down, and the method of applying the mother liquor is as follows: the reaction temperature is lowered to 18 degrees Celsius, and a large amount of solids are precipitated. At this temperature, the product mixed with the catalyst is filtered, and the mother liquor is applied mechanically next time. After dissolving the cake with ethyl acrylate, filter at room temperature, filter out the catalyst and use it mechanically next time, which can be applied 3 times. After the filtrate is precipitated, the crude product is recrystallized with 2.5 times the weight of ethyl acrylate to obtain a white product. The yield ...

Embodiment 3

[0048] The new synthesis process of canagliflozin comprises the following steps:

[0049] a. With 2-methylbenzoic acid as the starting material, use catalyst molecular sieves to support iron oxide, react with iodic acid and iodine with a molar multiple of 1.0 to generate intermediate-5-iodo-2-methylbenzoic acid, post-treatment process Adopt cold filtration after cooling down, and the method of applying the mother liquor is as follows: the reaction temperature is lowered to 22 degrees Celsius, and a large amount of solids are precipitated. At this temperature, the product mixed with the catalyst is filtered, and the mother liquor is applied mechanically next time. After dissolving the cake with ethyl acrylate, filter at room temperature, filter out the catalyst and use it mechanically next time, which can be applied 4 times. After the filtrate is precipitated, the crude product is recrystallized with 2.5 times the weight of ethyl acrylate to obtain a white product. The yield is ...

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PUM

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Abstract

The present invention discloses a new synthesis process of canagliflozin. The new synthesis process comprises: adopting 2-methyl benzoic acid as a starting raw material, and adopting a self-made catalyst, iodic acid and iodine to carry out a reaction to produce an intermediate 1, or adopting 2-methyl benzoic acid as a starting raw material, and adding liquid bromine under effects of a metal reagent and a catalyst to synthesize an intermediate 2; optionally selecting the intermediate 1 or 2 to carry out an acylation reaction with thionyl chloride, and then carrying out a Friedel-Crafts reaction to produce an intermediate 3; adopting ALPHA-D-glucose as a raw material, carrying out a reaction with pivaloyl chloride to protect all hydroxyl, and carrying out a reaction with zinc bromide and bromotrimethylsilane to produce an intermediate 4; linking the intermediate 3 and the intermediate 4 to produce an intermediate 5; and finally under an acid condition, removing the pivaloyl to produce the target compound. The new synthesis process has characteristics of high yield, mild condition, safety, reliability, cheap and easily available raw material, and easy production cost control, and is suitable for industrial production.

Description

technical field [0001] The invention relates to a new synthesis process of canagliflozin. Background technique [0002] Canagliflozin is the first SGLT2 inhibitor drug approved by the FDA. It can lower blood sugar by breaking down glucose and excreting it through the kidneys. It has broad prospects for the treatment of type 2 diabetes in adults. In addition to good blood sugar control, canagliflozin had a more significant weight loss effect, and compared with glimepiride, canagliflozin caused far fewer hypoglycemic events. [0003] The existing synthetic routes reported in the literature have harsh process conditions, such as high-temperature thermal filtration, high requirements for production equipment, and high industrialization costs; due to the long preparation route, the yield of each step is low, resulting in low overall yield and environmental pollution. The pollution is large, which is not conducive to industrial production. Therefore, it is necessary to provide a...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D409/10
CPCC07D409/10
Inventor 薛嵩
Owner HAIMEN RUIYI MEDICAL TECH