A method for the synthesis of carmelustatin

Abstract

This invention discloses a method for synthesizing carboxymethylcysteine, belonging to the field of organic synthesis technology. The method includes steps such as raw material dissolution, condensation reaction, neutralization crystallization, and centrifugal drying. The method of this invention directly neutralizes the reaction solution to the target pH with concentrated hydrochloric acid, stirs to precipitate crystals, and centrifuges and filters to directly obtain a qualified product, eliminating the need for multiple crystallization purifications. This reduces processes and equipment, increases yield, reduces material consumption, and significantly lowers process costs. The purity of the obtained product reaches over 99.90%, the residue on ignition content is as low as 0.05%, and the contents of cysteine, cystine, lactam, dicarboxymethylcysteine, and ammonium salts are extremely low; moreover, the yield reaches over 95%. The method of this invention operates under mild conditions, with no harmful gas emissions, and is equipment-friendly.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and in particular to a method for synthesizing carboxymethylcysteine. Background Technology

[0002] Carbocysteine ​​is a mucus thinner, a thiol-substituted derivative of cysteine. It is primarily used to treat thick sputum and difficulty expectorating caused by chronic bronchitis, bronchial asthma, tuberculosis, lung cancer, and other diseases. It has a wide range of applications, rapid oral absorption, and few side effects.

[0003] There are many reported processes for producing carboxymethylcysteine, which can use different starting materials and different processes to synthesize the final product. Among them, the synthesis process using anhydrous L-cysteine ​​hydrochloride or L-cysteine ​​hydrochloride monohydrate and chloroacetic acid as starting materials is more common.

[0004] For example, Chinese patent CN105418471A discloses a method for synthesizing carboxymethylcysteine. This method changes the existing two-pot reaction process to a one-pot reaction process, the low-temperature ammonia protection process to a room-temperature nitrogen-free protection process, and the two-step crystallization process to a one-step crystallization process. This method has at least the following disadvantages: due to the lack of nitrogen protection, L-cysteine ​​hydrochloride may be easily oxidized to cystine during the preparation process; impurity removal and decolorization treatments are required, which complicates the process and reduces the yield, with a maximum yield of about 91%; even so, there is still room for further improvement in the purity of the product; the molar amount of alkali used in this method is 4 to 5 times that of cysteine ​​hydrochloride, resulting in a higher content of residue on ignition in the obtained product, requiring purification or pulping of the crude product, which leads to a more complex process and a further decrease in yield.

[0005] For example, Chinese patent CN116143674A discloses a method for synthesizing high-purity carboxymethylcysteine. This method selects carbonates or bicarbonates as bases, and uses carbon dioxide gas generated during the reaction to protect L-cysteine ​​hydrochloride monohydrate from oxidation to cystine. After the condensation reaction, the addition of mercaptoethanol effectively removes cystine impurities. However, this method has at least the following drawbacks: the use of carbonates or bicarbonates during the condensation reaction releases a large amount of gas, increasing the pressure inside the reaction apparatus, requiring high-quality industrial equipment, posing a production hazard, and making it unsuitable for large-scale production; furthermore, the addition of mercaptoethanol after the condensation reaction has a strong, irritating odor, which is detrimental to human health and the environment; moreover, its yield is only around 90% at most, leaving considerable room for improvement; and finally, this method may result in excessive residue.

[0006] For example, Chinese patent CN106083673A discloses a preparation process for carboxymethylcysteine. This method has at least the following drawbacks: it requires the addition of several times the amount of ammonium bicarbonate as L-cysteine ​​hydrochloride monohydrate, resulting in high material consumption; it releases a large amount of carbon dioxide gas during the reaction, placing high demands on the equipment; and it uses liquid ammonia as an alkali to adjust the pH during the reaction. This compound is flammable, toxic, and highly corrosive. Although using liquid ammonia can reduce the residue on ignition, it can also easily increase the ammonium salt content in the product. Moreover, the industrial wastewater has a very high nitrogen content, increasing post-treatment costs. Summary of the Invention

[0007] The purpose of this invention is to provide a method for synthesizing carboxymethylcysteine ​​to solve the above-mentioned problems.

[0008] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0009] A method for synthesizing carboxymethylcysteine ​​includes the following steps

[0010] (1) Dissolving raw materials

[0011] Add water to the reaction vessel, and while stirring, add anhydrous L-cysteine ​​hydrochloride or L-cysteine ​​hydrochloride monohydrate and chloroacetic acid, stirring until dissolved;

[0012] (2) Condensation reaction

[0013] Add sodium hydroxide solution dropwise to the reaction vessel in step (1), control the temperature of the reaction solution to 38-43°C, and keep the reaction at the temperature for 0.5-1 hour after the alkali solution has been added.

[0014] (3) Neutralization crystallization

[0015] Add concentrated hydrochloric acid dropwise to the reaction solution in step (2), control the internal temperature at 50-70℃, adjust the pH value to 2.0-3.0, and keep it warm while stirring to crystallize for 1-3 hours;

[0016] (4) Centrifugal drying

[0017] Filter the crystallization liquid in step (3), add water to the wet product and stir evenly to form a slurry, filter again to obtain the wet product; put the wet product into a vacuum dryer and dry at 40-80℃ for 3-5 hours to obtain the dry product, cool and then crush and package.

[0018] Through extensive experimentation, the inventors discovered that the oxidation of cysteine ​​to cystine requires specific conditions. When the condensation reaction is slow, cysteine ​​readily forms cystine. However, if the reaction temperature is controlled within an appropriate range (38-43℃), the condensation reaction proceeds rapidly, making it less likely for cysteine ​​to form cystine. Therefore, it is unnecessary to use carbonates or bicarbonates to generate carbon dioxide or add mercaptoethanol to prevent cystine formation. Furthermore, if the reaction temperature is too high (above 43℃), not only cystine but also the content of lactams and dicarboxymethylcysteine ​​increases. In this invention, the reaction temperature can be controlled by adjusting the dropping rate of sodium hydroxide solution using a constant-pressure dropping funnel, thereby controlling the reaction rate and ultimately the impurity content.

[0019] As a preferred technical solution: in step (1), the molar ratio of L-cysteine ​​hydrochloride anhydrous or L-cysteine ​​hydrochloride monohydrate to chloroacetic acid is 1.0:0.95~1.2.

[0020] As a preferred technical solution: in step (1), the mass ratio of L-cysteine ​​hydrochloride anhydrous or L-cysteine ​​hydrochloride monohydrate to water is 1.0:3.0~5.0.

[0021] As a preferred technical solution: in step (2), the molar ratio of L-cysteine ​​hydrochloride anhydrous or L-cysteine ​​hydrochloride monohydrate to sodium hydroxide solution is 1.0:2.5~3.5.

[0022] Through numerous experiments, the inventors discovered that the reason why the ignition residue of the existing technology was substandard was that the amount of alkali used was too large, with the molar amount of alkali being 4 to 5 times that of cysteine ​​hydrochloride.

[0023] In neutralization and condensation reactions, 2.5–3 molar equivalents of alkali are required for the complete reaction of the cysteine ​​hydrochloride raw material. After obtaining the crude product through a single crystallization (a process that does not consume excess alkali), each recrystallization in the refining process consumes at least one molar equivalent of alkali. Existing technologies all require a process of crystallization and recrystallization to obtain the refined product. This invention only requires a single crystallization step after the reaction to obtain the refined product, eliminating the recrystallization refining step. Therefore, the entire process requires only 2.5–3.5 molar equivalents of alkali, thus solving the problem of excessive residue on ignition.

[0024] As a preferred technical solution: In step (3), neutralization and crystallization can be carried out to the target pH value. There is no need to continue adding concentrated hydrochloric acid until the crystals dissolve and then add sodium hydroxide solution to precipitate crystals.

[0025] The method of this invention involves, on the one hand, the neutralization and condensation reactions being carried out in one pot, with cysteine ​​hydrochloride reacting immediately after dissociation by alkali with chloroacetic acid; on the other hand, the reaction temperature is precisely controlled within the range of 38–43°C, resulting in a very slow rate of cysteine ​​to cystine formation and a low content of other impurities. Therefore, this invention eliminates the need for decolorization and impurity removal while still improving purity; it also eliminates the need for nitrogen protection and the addition of mercaptoethanol, and prevents L-cysteine ​​hydrochloride from being easily oxidized to cystine.

[0026] Compared with the prior art, the advantages of the present invention are as follows:

[0027] (1) The method of the present invention directly neutralizes the reaction solution to the target pH with concentrated hydrochloric acid, stirs to crystallize, centrifuges and filters to obtain qualified products directly, without the need for multiple crystallization and purification, and without the need for activated carbon decolorization and impurity removal, reducing the number of processes and equipment, increasing the yield and reducing material consumption.

[0028] (2) The synthesis method of the present invention combines the three steps of condensation reaction, neutralization reaction and crystallization into the same equipment, which optimizes the process, reduces the process equipment, and significantly reduces the process cost;

[0029] (3) The method of the present invention yields a product with a purity of 99.90 or higher, a residue content as low as 0.05% on ignition, and extremely low contents of cysteine, cystine, lactam, dicarboxymethylcysteine, and ammonium salt; and a yield of 95% or higher.

[0030] (4) The method of the present invention is mild, with no harmful gas emissions, and is equipment-friendly. Attached Figure Description

[0031] Figure 1 The HPLC chromatogram of the product obtained in Example 1;

[0032] Figure 2 The HPLC chromatogram of the product obtained in Example 2;

[0033] Figure 3 The HPLC chromatogram of the product obtained in Example 3;

[0034] Figure 4 The HPLC chromatogram of the product obtained in Comparative Example 1;

[0035] Figure 5 The HPLC chromatogram of the product obtained in Comparative Example 2;

[0036] Figure 6 The HPLC chromatogram of the product obtained in Comparative Example 3;

[0037] Figure 7 The HPLC chromatogram of the product obtained in Comparative Example 4;

[0038] Figure 8 The HPLC chromatogram of the product obtained in Comparative Example 5;

[0039] Figure 9 The image shows the HPLC chromatogram of the product obtained in Comparative Example 6. Detailed Implementation

[0040] To explain the technical content, objectives, and effects of the present invention in detail, the following specific embodiments are provided to further illustrate the content of the present invention. However, the content of the present invention is far more than the following examples.

[0041] Example 1

[0042] A method for synthesizing carboxymethylcysteine, the specific steps of which are as follows:

[0043] Add 350g of water to the reaction flask, then add 87.8g of cysteine ​​hydrochloride monohydrate and 49.6g of chloroacetic acid while stirring, and stir until completely dissolved. Add sodium hydroxide solution to the reaction flask, controlling the addition rate to maintain the reaction temperature at 38-39℃. Monitor the cysteine ​​reaction by HPLC until complete. Add concentrated hydrochloric acid to the reaction solution, controlling the addition rate and stirring speed, and adjust the pH to 2.8. Maintain the temperature and stir to allow crystallization for 1 hour. Allow to stand and cool to room temperature, filter to obtain a wet product. Add 200g of water to the wet product and stir until homogeneous to form a slurry. Stir for 1 hour, filter, rinse the filter cake with 50g of water, and dry the wet product at 50℃ to constant weight. Obtain 86.7g of carboxymethylcysteine ​​product, yield 96.8%, purity 99.91%, and residue on ignition 0.05%.

[0044] Example 2

[0045] A method for synthesizing carboxymethylcysteine, the specific steps of which are as follows:

[0046] Add 300g of water to the reaction flask, then add 87.8g of cysteine ​​hydrochloride monohydrate and 52.4g of chloroacetic acid while stirring, and stir until completely dissolved. Add sodium hydroxide solution to the reaction flask, controlling the addition rate and the reaction temperature to not exceed 40-41℃. Monitor the cysteine ​​reaction by HPLC until complete. Add concentrated hydrochloric acid to the reaction solution, controlling the addition rate and stirring speed, and adjust the pH to 2.5. Keep the mixture warm and stir to allow crystallization for 1.5 hours. Allow it to stand and cool to room temperature, then filter to obtain a wet product. Add 180g of water to the wet product and stir until it forms a slurry. Stir for 1 hour, filter, and rinse the filter cake with 50g of water. Dry the wet product at 50℃ to constant weight. Obtain 85.8g of carboxymethylcysteine ​​product, with a yield of 95.8%, purity of 99.90%, and residue on ignition of 0.06%.

[0047] Example 3

[0048] A method for synthesizing carboxymethylcysteine, the specific steps of which are as follows:

[0049] Add 400g of water to the reaction flask, then add 87.8g of cysteine ​​hydrochloride monohydrate and 50.0g of chloroacetic acid while stirring, and stir until completely dissolved. Add sodium hydroxide solution to the reaction flask, controlling the addition rate and the reaction temperature to not exceed 42-43℃. Monitor the cysteine ​​reaction by HPLC until complete. Add concentrated hydrochloric acid to the reaction solution, controlling the addition rate and stirring speed, and adjust the pH to 2.7. Maintain the temperature and stir to induce crystallization for 2 hours. Allow to stand and cool to room temperature, filter to obtain a wet product. Add 150g of water to the wet product and stir until homogeneous to form a slurry. Stir for 1 hour, filter, and rinse the filter cake with 50g of water. Dry the wet product at 50℃ to constant weight. Obtain 85.1g of carboxymethylcysteine ​​product, yield 95.0%, purity 99.90%, and residue on ignition 0.05%.

[0050] Comparative Example 1

[0051] Following the process route of patent CN105418471A: Add 310g of water to the reaction flask, then add 112.5g of anhydrous cysteine ​​hydrochloride and 72.0g of chloroacetic acid while stirring, and stir until completely dissolved; add sodium hydroxide solution to the reaction flask, controlling the addition rate and maintaining the reaction temperature at 30℃; monitor the cysteine ​​reaction by HPLC until complete; add concentrated hydrochloric acid to the reaction solution to adjust the pH to 6.5, heat to 70℃, add 1g of activated carbon, stir for decolorization for 0.5 hours, and filter while hot; then add concentrated hydrochloric acid dropwise to the flask while stirring to neutralize the decolorized solution until a large amount precipitates out. Crystallization was carried out, and concentrated hydrochloric acid was added dropwise until the crystals were just completely dissolved. Then, sodium hydroxide solution was added dropwise until the pH value reached 2.6. After cooling to room temperature, the crystals were allowed to stand for 10 hours to crystallize. The pH was precisely adjusted to 2.9 with stirring, and the crystals were allowed to stand for 8 hours to crystallize. The crystallization solution was filtered to obtain a crude wet product. 250g of purified water was added to the crude wet product and stirred until it became a slurry. After stirring and crystallizing for 30 minutes, the product was filtered. The filter cake was rinsed with 45g of water 3 times each time. The wet product was placed in a vacuum dryer and dried at 75°C for 7 hours until constant weight was obtained, yielding 114.7g of carboxymethylcysteine ​​product, with a yield of 89.7%, a purity of 99.67%, and a residue on ignition of 0.14%.

[0052] Comparative Example 2

[0053] Following the process route of patent CN105418471A: Add 300g of water to the reaction flask, then add 125.0g of cysteine ​​hydrochloride monohydrate and 72.0g of chloroacetic acid while stirring, and stir until completely dissolved; add sodium hydroxide solution to the reaction flask, controlling the addition rate and the reaction temperature to 30℃; monitor the cysteine ​​reaction by HPLC until complete; add concentrated hydrochloric acid to the reaction solution to adjust the pH to 6.5, heat to 65℃, add 1g of activated carbon, stir and decolorize for 1 hour, then filter while hot; add concentrated hydrochloric acid dropwise to the flask while stirring to neutralize the decolorized solution until a large amount of precipitate forms. The crystals were then dissolved by adding concentrated hydrochloric acid dropwise. Sodium hydroxide solution was then added dropwise until the pH reached 2.6. After cooling to room temperature, the crystals were allowed to stand for 12 hours to crystallize. The pH was then precisely adjusted to 2.9 with stirring, and the crystals were allowed to stand for another 6 hours. The crystallized liquid was filtered to obtain a crude wet product. 250g of purified water was added to the crude wet product and stirred until a slurry was formed. After stirring and crystallizing for 30 minutes, the product was filtered. The filter cake was rinsed three times with 45g of water each time. The wet product was then placed in a vacuum dryer and dried at 75℃ for 7 hours until constant weight was achieved, yielding 115.0g of carboxymethylcysteine ​​product, with a yield of 90.2%, a purity of 99.69%, and a residue on ignition of 0.18%.

[0054] Comparative Example 3

[0055] According to the process route of patent CN106083673A: (a) Take L-cysteine ​​hydrochloride monohydrate and solid chloroacetic acid, wherein the L-cysteine ​​hydrochloride monohydrate is 150g and the chloroacetic acid is taken at 60% of the mass of L-cysteine ​​hydrochloride monohydrate, i.e., 90g; (b) Put the reactants L-cysteine ​​hydrochloride monohydrate and chloroacetic acid into a flask, add 600g of water and stir to dissolve, and heat during the dissolution process to control the system temperature at about 20°C; (c) Use liquid ammonia and simultaneously add ammonium bicarbonate to adjust the volume. (d) After the reaction, adjust the pH of the system to 7.5, add 200g of ammonium bicarbonate, and control the temperature of the system at 45-50℃. React under stirring for 30 minutes; (e) After the reaction is complete, adjust the pH of the system to 6.0 with hydrochloric acid, and add 20g of activated carbon for decolorization and impurity adsorption. During the decolorization and impurity adsorption process, the temperature of the system is 75℃ and the treatment time is 30 minutes; (f) Filter, adjust the pH of the filtrate to 2.8 with hydrochloric acid, and control the entire adjustment process for about 20 minutes. Cool to obtain carboxymethylcysteine ​​crystals. (c) Dissolve the obtained carboxymethylcysteine ​​crystals with hydrochloric acid, and adjust the pH of the solution to 1.0. Use activated carbon for decolorization and impurity adsorption. The temperature of the decolorization and impurity adsorption process is 80℃ and the decolorization and impurity adsorption time is 30 minutes. Filter, and adjust the pH of the filtrate to 3.0. This adjustment process takes about 20 minutes. Cool again to obtain carboxymethylcysteine ​​crystals. 136.5g of carboxymethylcysteine ​​was obtained by drying to constant weight, with a yield of 89.2%, a purity of 99.66%, and a residue on ignition of 0.05%.

[0056] Comparative Example 4

[0057] According to the process route of patent CN106083673A: (a) Take L-cysteine ​​hydrochloride monohydrate and solid chloroacetic acid, wherein the L-cysteine ​​hydrochloride monohydrate is 150g and the chloroacetic acid is taken at 70% of the mass of L-cysteine ​​hydrochloride monohydrate, i.e., 105g; (b) Put the reactants L-cysteine ​​hydrochloride monohydrate and chloroacetic acid into a flask, add 450g of water and stir to dissolve, and heat during the dissolution process to control the system temperature at about 25°C; (c) Use liquid ammonia and add ammonium bicarbonate at the same time to adjust the temperature. The pH of the system was adjusted to 7.5, and 210g of ammonium bicarbonate was added. The temperature of the system was controlled at 45-50℃, and the reaction was carried out under stirring for 90 minutes. (d) After the reaction was complete, the pH of the system was adjusted to 6.4 with hydrochloric acid, and 20g of activated carbon was added for decolorization and impurity adsorption. During the decolorization and impurity adsorption process, the temperature of the system was 80℃, and the treatment time was 90 minutes. (e) The solution was filtered, and the pH of the filtrate was adjusted to 3.0 with hydrochloric acid. The entire adjustment process was controlled at approximately 30 minutes. After cooling, carboxymethylcysteine ​​crystals were obtained. (f) The obtained carboxymethylcysteine ​​crystals were dissolved in hydrochloric acid, and the pH of the solution was adjusted to 0.5. Activated carbon was used for decolorization and impurity adsorption. The temperature of the decolorization and impurity adsorption process was 75℃, and the decolorization and impurity adsorption time was 120 minutes. The solution was filtered, and the pH of the filtrate was adjusted to 2.8. This adjustment process took approximately 20 minutes. After cooling again, carboxymethylcysteine ​​crystals were obtained. After drying to constant weight, 139.7g of carboxymethylcysteine ​​was obtained, with a yield of 91.3%, a purity of 99.64%, and a residue on ignition of 0.04%.

[0058] Comparative Example 5

[0059] Add 350g of water to the reaction flask, then add 87.8g of cysteine ​​hydrochloride monohydrate and 49.6g of chloroacetic acid while stirring, and stir until completely dissolved. Add sodium hydroxide solution to the reaction flask, controlling the addition rate to maintain the reaction temperature at 35-36℃. Monitor the cysteine ​​reaction by HPLC until complete. Add concentrated hydrochloric acid to the reaction solution, controlling the addition rate and stirring speed, and adjust the pH to 2.8. Maintain the temperature and stir to allow crystallization for 1 hour. Allow to stand and cool to room temperature, filter to obtain a wet product. Add 200g of water to the wet product and stir until homogeneous to form a slurry. Stir for 1 hour, filter, and rinse the filter cake with 50g of water. Dry the wet product at 50℃ to constant weight. Obtain 85.3g of carboxymethylcysteine ​​product, yield 95.3%, purity 99.81%, and residue on ignition 0.06%.

[0060] Comparative Example 6

[0061] Add 350g of water to the reaction flask, then add 87.8g of cysteine ​​hydrochloride monohydrate and 49.6g of chloroacetic acid while stirring, and stir until completely dissolved. Add sodium hydroxide solution to the reaction flask, controlling the addition rate to maintain the reaction temperature at 45-46℃. Monitor the cysteine ​​reaction by HPLC until complete. Add concentrated hydrochloric acid to the reaction solution, controlling the addition rate and stirring speed, and adjust the pH to 2.8. Maintain the temperature and stir to allow crystallization for 1 hour. Allow to stand and cool to room temperature, filter to obtain a wet product. Add 200g of water to the wet product and stir until homogeneous to form a slurry. Stir for 1 hour, filter, and rinse the filter cake with 50g of water. Dry the wet product at 50℃ to constant weight. Obtain 84.9g of carboxymethylcysteine ​​product, yield 94.8%, purity 99.79%, and residue on ignition 0.05%.

[0062] The products obtained in Examples 1 to 3 and Comparative Examples 1 to 4 were subjected to HPLC purity testing under the conditions described in Table 1 below.

[0063] Table 1 HPLC detection conditions

[0064]

[0065] The results obtained are as follows: Figures 1 to 9 As shown.

[0066] Impurities and ignition residues were detected in the products obtained in Examples 1 to 3 and Comparative Examples 1 to 6, and the results are shown in Table 2.

[0067] The testing conditions and standards for ignition residue, chloride ions and ammonium salts are in accordance with the requirements of the 2025 edition of the Chinese Pharmacopoeia.

[0068] The method for testing the residue on ignition in General Chapter 0841 of the 2025 edition of the Chinese Pharmacopoeia is as follows: Take 1.0 g of sample and place it in a platinum crucible that has been ignited to constant weight. Weigh it accurately, ignite it slowly until completely carbonized, cool it, add 1.0 mL of sulfuric acid to moisten it, heat it at a low temperature until the sulfuric acid vapor is completely removed, then ignite it at 700-800℃ to completely ashed it. Transfer it to a desiccator, cool it, weigh it accurately, and then ignite it again at 700-800℃ to constant weight. The residue should not exceed 0.2%.

[0069] Table 2. Impurity detection results of products obtained from each embodiment and comparative example.

[0070]

[0071] In Table 2, serial numbers 1-9 represent the products of Examples 1 to 3 and Comparative Examples 1 to 6, respectively.

[0072] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A method for synthesizing carboxymethylcysteine, characterized in that, Includes the following steps: (1) Dissolving raw materials Add water to the reaction vessel, and while stirring, add anhydrous L-cysteine ​​hydrochloride or L-cysteine ​​hydrochloride monohydrate and chloroacetic acid, stirring until dissolved; (2) Condensation reaction Add sodium hydroxide solution dropwise to the reaction vessel in step (1), control the temperature of the reaction solution to 38-43°C, and keep the reaction at the temperature for 0.5-1 hour after the alkali solution has been added. (3) Neutralization crystallization Add concentrated hydrochloric acid dropwise to the reaction solution in step (2), control the internal temperature at 50-70℃, adjust the pH value to 2.0-3.0, and keep it warm while stirring to crystallize for 1-3 hours; (4) Centrifugal drying Filter the crystallization liquid in step (3), add water to the wet product and stir evenly to form a slurry, filter again to obtain the wet product; put the wet product into a vacuum dryer and dry at 40-80℃ for 3-5 hours to obtain the dry product, cool and then crush and package.

2. The method according to claim 1, characterized in that: In step (1), the molar ratio of L-cysteine ​​hydrochloride anhydrous or L-cysteine ​​hydrochloride monohydrate to chloroacetic acid is 1.0:0.95-1.

2.

3. The method according to claim 1, characterized in that: In step (1), the mass ratio of L-cysteine ​​hydrochloride anhydrous or L-cysteine ​​hydrochloride monohydrate to water is 1.0:3.0 to 5.

0.

4. The method according to claim 1, characterized in that: In step (2), the molar ratio of L-cysteine ​​hydrochloride anhydrous or L-cysteine ​​hydrochloride monohydrate to sodium hydroxide solution is 1.0:2.5-3.

5.

5. The method for synthesizing carboxymethylcysteine ​​according to claim 1, characterized in that: In step (3), neutralize and crystallize to the target pH value. There is no need to continue adding concentrated hydrochloric acid until the crystals dissolve and then add sodium hydroxide solution to precipitate crystals.

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