A kind of preparation method of tranexamic acid

A technology of tranexamic acid and aminomethylcyclohexanecarboxylic acid, which is applied in the field of preparation of tranexamic acid, can solve the problem that the total yield is only 14%, and achieve reduced raw material consumption, high yield, and reduced operation The effect of steps

Active Publication Date: 2014-10-08
VALIANT CO LTD
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  • Abstract
  • Description
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  • Application Information

AI Technical Summary

Problems solved by technology

This method has only 14% total yield because there is no transformation step

Method used

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  • A kind of preparation method of tranexamic acid

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Effect test

Embodiment 1

[0034] 1. Catalytic hydrogenation

[0035] In a 2L autoclave, add 234g 4-(acetamidomethyl)benzoic acid, 1000mL deionized water, 50.9g NaOH, 23g Raney nickel, N 2 Substitution, hydrogen replacement, under the conditions of 100°C and 6MPa, react until there is no pressure drop, and then react for 3h. Cool down to room temperature, remove all remaining hydrogen, take it out with a suction filter bottle, filter, remove the catalyst, rinse the catalyst with water to obtain a cis-trans mixture of potassium salt of 4-(acetylaminomethyl)cyclohexylformate.

[0036] 2. Deprotection transformation into salt

[0037] Add 97.0g NaOH to the 4-(acetylaminomethyl) cyclohexyl formic acid potassium salt cis-trans mixture, stir to dissolve, pass N 2 , distill water at 130°C until there is almost no distillate, heat up to 200°C in an oil bath, the reaction solution gradually solidifies and dries, and continues to bake at this temperature for 16 hours to obtain a dry solid. Cool down to room te...

Embodiment 2

[0041] 1. Catalytic hydrogenation

[0042] In a 2L autoclave, add 234g 4-(acetamidomethyl)benzoic acid, 1000mL deionized water, 50.9g NaOH, 23g Raney nickel, N 2 Substitution, hydrogen replacement, under the conditions of 180°C and 15MPa, react until there is no pressure drop, and then react for 3h. Cool down to room temperature, remove all remaining hydrogen, take it out with a suction filter bottle, filter, remove the catalyst, rinse the catalyst with water to obtain a cis-trans mixture of potassium salt of 4-(acetylaminomethyl)cyclohexylformate.

[0043] 2. Deprotection transformation into salt

[0044] Add 97.0g NaOH to the 4-(acetylaminomethyl) cyclohexyl formic acid potassium salt cis-trans mixture, stir to dissolve, pass N 2 , distill water at 150°C until there is almost no distillate, heat up to 280°C in an oil bath, the reaction solution gradually solidifies and dries, and continues to bake at this temperature for 24 hours to obtain a dry solid. Cool down to room t...

Embodiment 3

[0048] 1. Hydrogenation

[0049] 2L autoclave, add 234g 4-(acetamidomethyl)benzoic acid, 1000mL deionized water, 61g NaOH, 25g Raney nickel, N 2Substitution, hydrogen replacement, at 150°C, 12MPa, react until there is no pressure drop, and then react for 3h. Cool down to room temperature, remove all remaining hydrogen, take it out with a suction filter bottle, filter, remove the catalyst, rinse the catalyst with water to obtain a cis-trans mixture of potassium salt of 4-(acetylaminomethyl)cyclohexylformate.

[0050] 2. Deprotection transformation into salt (best)

[0051] In 4-(acetamidomethyl) cyclohexyl formic acid potassium salt cis-trans mixture, add 83g NaOH, stir to dissolve, logical N 2 , Distill water at 130°C until there is almost no distillate, heat up to an oil bath at 230°C, the reaction solution gradually solidifies and dries, and continues to bake at this temperature for 18 hours to obtain a dry solid. Cool down to room temperature and add 1600mL of water, sti...

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Abstract

The invention relates to a tranexamic acid high-efficiency production method which comprises the following steps: performing hydrogenation reduction on 4-(acetylaminomethyl)benzoic acid used as an initial raw material, filtering the hydrogenation solution to remove a catalyst, distilling until the reaction solution is cured, heating, and baking to perform transformation; and dissolving with water, regulating the reaction solution to neutral with acid, adding p-toluenesulfonic acid to perform salification, filtering, performing resin exchange with a weak base anion-exchange resin, distilling the eluate until a large amount of solids are precipitated, adding a right amount of ethanol to crystallize, cooling, filtering, washing, and drying to obtain tranexamic acid. For the tranexamic acid produced by the method, the cis-compound content is lower than 0.05%, and the quality completely meets pharmacopeia standards at home and abroad and is higher than the quality of products currently reported in China. The production route provided by the invention has the advantages of fewer steps, simple operation process, high yield, energy saving, environment friendliness and the like.

Description

technical field [0001] The invention relates to a preparation method of tranexamic acid. Background technique [0002] The chemical name of tranexamic acid is trans-p-aminomethylcyclohexanecarboxylic acid (referred to as trans-AMCA or AMCA). It is an effective hemostatic agent and has been widely used clinically in China, and it is included in the new edition of the Chinese Pharmacopoeia. The hemostatic effect is only effective for the trans form, while the cis-AMCA is almost ineffective, and the former is about 50 times stronger than the latter. [0003] At present, there are many synthetic methods about tranexamic acid reported abroad. One method is to use aminomethylbenzoic acid as a starting material, undergo hydrogenation reduction, transformation, and refine to obtain tranexamic acid products. In this method, due to the direct catalytic hydrogenation of aminotoluic acid, there are many deaminated impurities, difficult purification, low production efficiency, and high...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C229/46C07C227/18C07C227/20C07C227/40
Inventor 孙宝佳孟凡民艾文吴宪于璐杨光鲁旭童
Owner VALIANT CO LTD
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