CN105017044A - Preparation method of trans-4-aminomethylcyclohexanecarboxylic acid - Google Patents
Preparation method of trans-4-aminomethylcyclohexanecarboxylic acid Download PDFInfo
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- CN105017044A CN105017044A CN201510480125.3A CN201510480125A CN105017044A CN 105017044 A CN105017044 A CN 105017044A CN 201510480125 A CN201510480125 A CN 201510480125A CN 105017044 A CN105017044 A CN 105017044A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/36—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by hydrogenation of carbon-to-carbon unsaturated bonds
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/04—Formation of amino groups in compounds containing carboxyl groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/16—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions not involving the amino or carboxyl groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/08—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/313—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of doubly bound oxygen containing functional groups, e.g. carboxyl groups
Abstract
The invention discloses a preparation method of trans-4-aminomethylcyclohexanecarboxylic acid. Specifically, the method includes the following steps of 1, catalytic hydrogenation of 4-hydroxybenzoic acid; 2, esterification of 4-hydroxyl cyclohexyl formic acid; 3, oxidation of 4-hydroxycyclohexyl formic ether; 4, condensation of 4-oxo cyclohexyl formic ether and nitromethane; 5, catalytic hydrogenation of 4-nitryl methylene cyclohexyl formic ether; 6, hydrolysis and conversion of 4-aminomethyl cyclohexyl formic ether. Compared with the prior art, raw materials used for the preparation method are lower in price and easier to obtain, cost is low, side reactions are fewer, and the yield is higher; meanwhile, the method is easy and convenient to operate and lower in environmental pollution, and has wide development and application prospects.
Description
Technical field
The invention belongs to technical field of medicine synthesis, be specifically related to a kind of preparation method of trans-4-aminomethyl hexahydrobenzoic acid.
Background technology
The trans relevant information to aminomethyl hexahydrobenzoic acid is as described below:
Chinese: trans-4-aminomethyl hexahydrobenzoic acid, also known as tranexamic acid (Tranexamic acid) or tranamic acid;
English name:
trans-4-aminomethylcyclohexanecarboxylic acid;
CAS：1197-18-8；
Structural formula:
;
Molecular formula: C
8h
15nO
2;
Molecular weight: 157.21;
Proterties: white crystalline powder; Odorless, mildly bitter flavor; Soluble in water, be insoluble to alcohol and chloroform.
The clinical application of tranamic acid is with a long history, and preparation method is numerous.Domestic production trans-4-aminomethyl hexahydrobenzoic acid mainly contains two kinds of methods, " the national bulk drug technique compilation " 510th ~ 512 pages of State Pharmaceutical Administration chief editor in 1980 publication gives operational path as follows and working method, and wherein described preparation method's genus proposes first:
First method synthetic route:
；
First method take methyl acrylate as raw material, through cyclization, cyaniding, catalytic hydrogenation, hydrolysis, conversion, obtain trans to aminomethyl hexahydrobenzoic acid, but the method needs the prussiate and the heavy metal copper that use severe toxicity, the requirement for security and the disposal of three wastes is higher;
Second method synthetic route:
；
Second method take para-amino-methyl-benzoic acid as raw material, through catalytic hydrogenation, conversion, obtain trans to aminomethyl hexahydrobenzoic acid, but the method needs to use expensive platinum dioxide (PtO
2) as the catalyzer of catalytic hydrogenation step, cause production cost higher.
Given this, a kind of safe and effective, environmental protection is needed at present badly and the preparation method of the trans-4-aminomethyl hexahydrobenzoic acid of economy and facility.
Summary of the invention
In order to solve the problem, the invention discloses a kind of preparation method of trans-4-aminomethyl hexahydrobenzoic acid.The method adopts P-hydroxybenzoic acid cheap and easy to get to be raw material, first through catalytic hydrogenation and esterification, obtain 4-hydroxy cyclohexylphenyl carbamate, secondly through oxidation, obtain 4-oxocyclohex carbamate, then under the catalysis of alkali with Nitromethane 99Min. addition, obtain 4-Nitromethylene hexahydrobenzoic acid ester, then through catalytic hydrogenation, obtain 4-aminomethyl hexahydrobenzoic acid ester, last in the basic conditions through hydrolysis and conversion, obtain trans-4-aminomethyl hexahydrobenzoic acid.
Specifically, this preparation method comprises the steps:
1) catalytic hydrogenation of 4-HBA: according to 4-HBA: alkali: the weight ratio of Raney's nickel=20:10 ~ 12:2 ~ 3,4-HBA, alkali, Raney's nickel and the water as solvent is added in hydriding reactor, pass into hydrogen to eliminate air in still, it is 80 ~ 90 DEG C in temperature, pressure is react under the condition of 5 ~ 6Mpa, until stopped reaction when no longer inhaling hydrogen, cooling discharging, filter, filtrate is adjusted to pH=2 with acid, filter separate out solid, obtain 4-hydroxy-cyclohexyl formic acid, not purified be directly used in next step reaction;
2) esterification of 4-hydroxy-cyclohexyl formic acid: according to 4-HBA: tosic acid: the weight ratio of alcohol=10:1:20,4-hydroxy-cyclohexyl formic acid, tosic acid, alcohol and the toluene as solvent obtained in step 1) is added in reactor, heating reflux reaction 8 ~ 10 hours under agitation, be cooled to 50 DEG C, layering is stirred after adding water, concentrating under reduced pressure after toluene layer washing, obtains 4-hydroxy cyclohexylphenyl carbamate;
3) oxidation of 4-hydroxy cyclohexylphenyl carbamate: according to 4-hydroxy cyclohexylphenyl carbamate: the weight ratio of clorox=10:45, in reactor, temperature is drip clorox in the dichloromethane solution of the 4-hydroxy cyclohexylphenyl carbamate of 10 ~ 15 DEG C, dropwise rear stirring 1 ~ 1.5 hour, add Virahol termination reaction, stratification, concentrating under reduced pressure after dichloromethane layer washing, obtains 4-oxocyclohex carbamate;
4) condensation of 4-oxocyclohex carbamate and Nitromethane 99Min.: according to 4-oxocyclohex carbamate: Nitromethane 99Min.: the weight ratio of alkali=50:19 ~ 20:0.6 ~ 1.5,4-oxocyclohex carbamate, Nitromethane 99Min., alkali and the ethanol as solvent is added in reactor, in 0 ~ 3 DEG C of stirring reaction 4 ~ 5h, then pH=4 is adjusted to acid, concentrating under reduced pressure, layering is stirred add water and methylene dichloride in residue after, concentrating under reduced pressure after dichloromethane layer washing, obtains 4-Nitromethylene hexahydrobenzoic acid ester;
5) catalytic hydrogenation of 4-Nitromethylene hexahydrobenzoic acid ester: according to 4-Nitromethylene hexahydrobenzoic acid ester: the weight ratio of Raney's nickel=10:1,4-Nitromethylene hexahydrobenzoic acid ester, Raney's nickel and the methyl alcohol as solvent is added in hydriding reactor, pass into hydrogen to eliminate air in still, be 70 ~ 80 DEG C in temperature, pressure is react under the condition of 0.08 ~ 0.1MPa, until stopped reaction when no longer inhaling hydrogen, cooling discharging, filter, filtrate reduced in volume, obtains 4-aminomethyl hexahydrobenzoic acid ester; With
6) 4-aminomethyl hexahydrobenzoic acid ester hydrolysis and conversion: according to 4-aminomethyl hexahydrobenzoic acid ester: the weight ratio of hydrated barta=30:63 ~ 65,4-aminomethyl hexahydrobenzoic acid ester, hydrated barta and the water as solvent is added in autoclave, be warming up to 220 ~ 230 DEG C and react 8 ~ 10h, after reaction terminates, water dilution is added in reactor, and be adjusted to pH=5.5 ~ 6 with dilute sulphuric acid, filter, gac boiling decoloring is added in filtrate, filter, filtrate reduced in volume, obtains trans-4-aminomethyl hexahydrobenzoic acid.
Preferably, in technique scheme, described in step 1), acid is dilute hydrochloric acid or dilute sulphuric acid, preferred dilute sulphuric acid.
Preferably, in technique scheme, alkali described in step 1) is sodium hydroxide or potassium hydroxide, preferred sodium hydroxide.
Preferably, in technique scheme, step 2) described in alcohol be selected from C1 ~ C8 fatty alcohol any one, particular methanol, ethanol, Virahol or the trimethyl carbinol, more preferably methyl alcohol or ethanol, most preferred ethanol.
Preferably, in technique scheme, described in step 4), acid is dilute hydrochloric acid or dilute sulphuric acid, preferred dilute sulphuric acid.
Preferably, in technique scheme, alkali described in step 4) is sodium hydroxide or potassium hydroxide, preferred sodium hydroxide, is more preferably mixed with the aqueous solution that mass concentration is 30% in advance before dosing.
With in prior art for the preparation of compared with the method for trans-4-aminomethyl hexahydrobenzoic acid, the raw material that preparation method of the present invention uses is more cheap and easy to get, and cost is low, and side reaction is less, and yield is higher; Meanwhile, the method is easy and simple to handle, and less to the pollution of environment, possesses wide development and application prospect.
Accompanying drawing explanation
Fig. 1 is the synthetic route of trans-4-aminomethyl hexahydrobenzoic acid in the present invention.
Fig. 2 is the infrared spectrogram of the trans-4-aminomethyl hexahydrobenzoic acid of preparation in embodiment 1.
Embodiment
Make further instructions the present invention below in conjunction with specific embodiment, but be understandable that, protection scope of the present invention is not limited to the following example.
Embodiment one: the preparation (synthetic route as shown in Figure 1) of trans-4-aminomethyl hexahydrobenzoic acid.
(1) catalytic hydrogenation of 4-HBA: add 4-HBA 100g, water 500mL, sodium hydroxide 50g and Raney's nickel 10g in hydriding reactor, pass into hydrogen to eliminate air in still, be 80 DEG C in temperature, pressure is react under the condition of 5MPa, until stopped reaction when no longer inhaling hydrogen, cooling discharging, filter, filtrate is adjusted to pH=2 with dilute sulphuric acid, filters the solid of separating out, obtain 4-hydroxy-cyclohexyl formic acid, not purified be directly used in next step reaction.
(2) esterification of 4-hydroxy-cyclohexyl formic acid: add 4-hydroxy-cyclohexyl formic acid, toluene 500mL, tosic acid 10g and ethanol 200g in reactor, heating reflux reaction 8h under agitation, be cooled to 50 DEG C, add water 300mL, stir layering, once, concentrating under reduced pressure, obtains 4-hydroxy-cyclohexyl ethyl formate 112g in toluene layer washing.
(3) oxidation of 4-hydroxy-cyclohexyl ethyl formate: add 4-hydroxy-cyclohexyl ethyl formate 100g and methylene dichloride 100mL in reactor, drips clorox 450g in 10 DEG C.Add and stir 1h, add Virahol 10g termination reaction, stratification, once, anhydrous sodium sulfate drying, concentrating under reduced pressure, obtains 4-oxocyclohexyl ethyl formate 87g in dichloromethane layer washing.
(4) condensation of 4-oxocyclohexyl ethyl formate and Nitromethane 99Min.: add 4-oxocyclohexyl ethyl formate 50g, Nitromethane 99Min. 19g, ethanol 150mL and 30% aqueous sodium hydroxide solution 5g in reactor, in 3 DEG C of stirring reaction 4h, dilute sulphuric acid is adjusted to pH=4, after concentrating under reduced pressure, in residue, add water 80mL and methylene dichloride 100mL, stir layering, dichloromethane layer washing once, anhydrous sodium sulfate drying, concentrating under reduced pressure, obtains 4-Nitromethylene cyclohexyl ethyl formate 60g.
(5) catalytic hydrogenation of 4-Nitromethylene cyclohexyl ethyl formate: add 4-Nitromethylene cyclohexyl ethyl formate 20g, methyl alcohol 100mL and Raney's nickel 2g in hydriding reactor, pass into hydrogen to eliminate air in still, it is 70 DEG C in temperature, pressure is react under the condition of 0.08MPa, until stopped reaction when no longer inhaling hydrogen, cooling discharging, filters, filtrate reduced in volume, obtains 4-aminomethyl cyclohexyl ethyl formate 16g.
(6) hydrolysis of 4-aminomethyl cyclohexyl ethyl formate and conversion: add 4-aminomethyl cyclohexyl ethyl formate 30g, water 70mL and hydrated barta 63g in autoclave, be warming up to 220 DEG C and react 10h, after reaction terminates, in reactor, add water 150mL, and be adjusted to pH=5.5 with dilute sulphuric acid, filter, in filtrate, add gac boiling decoloring, filter, filtrate reduced in volume, obtain trans-4-aminomethyl hexahydrobenzoic acid 16.8g, its infrared spectrogram as shown in Figure 2.
Embodiment two: the preparation of trans-4-aminomethyl hexahydrobenzoic acid.
(1) catalytic hydrogenation of 4-HBA: add 4-HBA 100g, water 500mL, sodium hydroxide 60g and Raney's nickel 15g in hydriding reactor, pass into hydrogen to eliminate air in still, be 90 DEG C in temperature, pressure is react under the condition of 6MPa, until stopped reaction when no longer inhaling hydrogen, cooling discharging, filter, filtrate is adjusted to pH=2 with dilute sulphuric acid, filters the solid of separating out, obtain 4-hydroxy-cyclohexyl formic acid, not purified be directly used in next step reaction.
(2) esterification of 4-hydroxy-cyclohexyl formic acid: add 4-hydroxy-cyclohexyl formic acid, toluene 500mL, tosic acid 10g and ethanol 200g in reactor, heating reflux reaction 10h under agitation, be cooled to 50 DEG C, add water 500mL, stir layering, once, concentrating under reduced pressure, obtains 4-hydroxy-cyclohexyl ethyl formate 112g in toluene layer washing.
(3) oxidation of 4-hydroxy-cyclohexyl ethyl formate: add 4-hydroxy-cyclohexyl ethyl formate 100g and methylene dichloride 200mL in reactor, drips clorox 450g in 15 DEG C.Add and stir 1.5h, add Virahol 10g termination reaction, stratification, once, anhydrous sodium sulfate drying, concentrating under reduced pressure, obtains 4-oxocyclohexyl ethyl formate 87g in dichloromethane layer washing.
(4) condensation of 4-oxocyclohexyl ethyl formate and Nitromethane 99Min.: add 4-oxocyclohexyl ethyl formate 50g, Nitromethane 99Min. 20g, ethanol 190mL and 30% aqueous sodium hydroxide solution 2g in reactor, in 0 DEG C of stirring reaction 5h, dilute sulphuric acid is adjusted to pH=4, after concentrating under reduced pressure, in residue, add water 60mL and methylene dichloride 100mL, stir layering, dichloromethane layer washing once, anhydrous sodium sulfate drying, concentrating under reduced pressure, obtains 4-Nitromethylene cyclohexyl ethyl formate 60g.
(5) catalytic hydrogenation of 4-Nitromethylene cyclohexyl ethyl formate: add 4-Nitromethylene cyclohexyl ethyl formate 20g, methyl alcohol 130mL and Raney's nickel 2g in hydriding reactor, pass into hydrogen to eliminate air in still, it is 80 DEG C in temperature, pressure is react under the condition of 0.1MPa, until stopped reaction when no longer inhaling hydrogen, cooling discharging, filters, filtrate reduced in volume, obtains 4-aminomethyl cyclohexyl ethyl formate 16g.
(6) hydrolysis of 4-aminomethyl cyclohexyl ethyl formate and conversion: add 4-aminomethyl cyclohexyl ethyl formate 30g, water 50mL and hydrated barta 65g in autoclave, be warming up to 230 DEG C and react 8h, after reaction terminates, in reactor, add water 200mL, and be adjusted to pH=6 with dilute sulphuric acid, filter, gac boiling decoloring is added in filtrate, filter, filtrate reduced in volume, obtains trans-4-aminomethyl hexahydrobenzoic acid 16.8g.
Claims (10)
1. a preparation method for trans-4-aminomethyl hexahydrobenzoic acid, it comprises the steps:
1) catalytic hydrogenation of 4-HBA: according to 4-HBA: alkali: the weight ratio of Raney's nickel=20:10 ~ 12:2 ~ 3,4-HBA, alkali, Raney's nickel and the water as solvent is added in hydriding reactor, pass into hydrogen to eliminate air in still, it is 80 ~ 90 DEG C in temperature, pressure is react under the condition of 5 ~ 6Mpa, until stopped reaction when no longer inhaling hydrogen, cooling discharging, filter, filtrate is adjusted to pH=2 with acid, filter separate out solid, obtain 4-hydroxy-cyclohexyl formic acid, not purified be directly used in next step reaction;
2) esterification of 4-hydroxy-cyclohexyl formic acid: according to 4-HBA: tosic acid: the weight ratio of alcohol=10:1:20,4-hydroxy-cyclohexyl formic acid, tosic acid, alcohol and the toluene as solvent obtained in step 1) is added in reactor, heating reflux reaction 8 ~ 10 hours under agitation, be cooled to 50 DEG C, layering is stirred after adding water, concentrating under reduced pressure after toluene layer washing, obtains 4-hydroxy cyclohexylphenyl carbamate;
3) oxidation of 4-hydroxy cyclohexylphenyl carbamate: according to 4-hydroxy cyclohexylphenyl carbamate: the weight ratio of clorox=10:45, in reactor, temperature is drip clorox in the dichloromethane solution of the 4-hydroxy cyclohexylphenyl carbamate of 10 ~ 15 DEG C, dropwise rear stirring 1 ~ 1.5 hour, add Virahol termination reaction, stratification, concentrating under reduced pressure after dichloromethane layer washing, obtains 4-oxocyclohex carbamate;
4) condensation of 4-oxocyclohex carbamate and Nitromethane 99Min.: according to 4-oxocyclohex carbamate: Nitromethane 99Min.: the weight ratio of alkali=50:19 ~ 20:0.6 ~ 1.5,4-oxocyclohex carbamate, Nitromethane 99Min., alkali and the ethanol as solvent is added in reactor, in 0 ~ 3 DEG C of stirring reaction 4 ~ 5h, then pH=4 is adjusted to acid, concentrating under reduced pressure, layering is stirred add water and methylene dichloride in residue after, concentrating under reduced pressure after dichloromethane layer washing, obtains 4-Nitromethylene hexahydrobenzoic acid ester;
5) catalytic hydrogenation of 4-Nitromethylene hexahydrobenzoic acid ester: according to 4-Nitromethylene hexahydrobenzoic acid ester: the weight ratio of Raney's nickel=10:1,4-Nitromethylene hexahydrobenzoic acid ester, Raney's nickel and the methyl alcohol as solvent is added in hydriding reactor, pass into hydrogen to eliminate air in still, be 70 ~ 80 DEG C in temperature, pressure is react under the condition of 0.08 ~ 0.1MPa, until stopped reaction when no longer inhaling hydrogen, cooling discharging, filter, filtrate reduced in volume, obtains 4-aminomethyl hexahydrobenzoic acid ester; With
6) 4-aminomethyl hexahydrobenzoic acid ester hydrolysis and conversion: according to 4-aminomethyl hexahydrobenzoic acid ester: the weight ratio of hydrated barta=30:63 ~ 65,4-aminomethyl hexahydrobenzoic acid ester, hydrated barta and the water as solvent is added in autoclave, be warming up to 220 ~ 230 DEG C and react 8 ~ 10h, after reaction terminates, water dilution is added in reactor, and be adjusted to pH=5.5 ~ 6 with dilute sulphuric acid, filter, gac boiling decoloring is added in filtrate, filter, filtrate reduced in volume, obtains trans-4-aminomethyl hexahydrobenzoic acid.
2. preparation method according to claim 1, is characterized in that, step 1) and 4) described in acid be dilute hydrochloric acid or dilute sulphuric acid.
3. preparation method according to claim 2, is characterized in that, step 1) and 4) described in acid be dilute sulphuric acid.
4. preparation method according to claim 1, is characterized in that, alkali described in step 1) is sodium hydroxide or potassium hydroxide.
5. preparation method according to claim 4, is characterized in that, alkali described in step 1) is sodium hydroxide.
6. preparation method according to claim 1, is characterized in that, step 2) described in alcohol be methyl alcohol or ethanol.
7. preparation method according to claim 5, is characterized in that, step 2) described in alcohol be ethanol.
8. preparation method according to claim 1, is characterized in that, alkali described in step 4) is sodium hydroxide or potassium hydroxide.
9. preparation method according to claim 8, is characterized in that, alkali described in step 4) is sodium hydroxide.
10. preparation method according to claim 9, is characterized in that, described sodium hydroxide is mixed with the aqueous solution that mass concentration is 30% before dosing in advance.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110627752A (en) * | 2018-06-25 | 2019-12-31 | 新发药业有限公司 | Preparation method of 3-aminomethyl tetrahydrofuran |
| CN114163449A (en) * | 2021-12-20 | 2022-03-11 | 大连奇凯医药科技有限公司 | Preparation and characterization method of 1,2,4, 5-cyclohexane tetracarboxylic dianhydride |
| CN114181077A (en) * | 2021-12-20 | 2022-03-15 | 风火轮(上海)生物科技有限公司 | Method for synthesizing tranexamic acid |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110627752A (en) * | 2018-06-25 | 2019-12-31 | 新发药业有限公司 | Preparation method of 3-aminomethyl tetrahydrofuran |
| CN110627752B (en) * | 2018-06-25 | 2021-08-17 | 新发药业有限公司 | Preparation method of 3-aminomethyl tetrahydrofuran |
| CN114163449A (en) * | 2021-12-20 | 2022-03-11 | 大连奇凯医药科技有限公司 | Preparation and characterization method of 1,2,4, 5-cyclohexane tetracarboxylic dianhydride |
| CN114181077A (en) * | 2021-12-20 | 2022-03-15 | 风火轮(上海)生物科技有限公司 | Method for synthesizing tranexamic acid |
| CN114181077B (en) * | 2021-12-20 | 2024-02-27 | 风火轮(上海)生物科技有限公司 | Method for synthesizing tranexamic acid |
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