Preparation method of 2-(N-morpholino) ethanesulfonic acid monohydrate

Abstract

The invention provides a preparation method of 2-(N-morpholino) ethanesulfonic acid monohydrate, and relates to the technical field of preparation of sulfonic acid organic matters. The preparation method comprises the following steps: mixing sodium 2-chloroethanesulfonate, water and morpholine, and carrying out a coupling reaction to obtain a coupling reaction product containing sodium 2-(N-morpholino) ethanesulfonate and hydrogen chloride; the coupling reaction product and organic amine are mixed for an acid-base neutralization reaction, and an acid-base neutralization reaction product is obtained; mixing the acid-base neutralization reaction product and an acid compound, and acidifying to obtain an acidified product; and concentrating the acidified product to obtain a concentrated product, mixing the concentrated product with an organic solvent, repeatedly executing for multiple times, and filtering and drying the obtained solution to obtain the 2-(N-morpholino) ethanesulfonic acid monohydrate. According to the preparation method, simple and easily available basic raw materials are adopted, and a specific reagent is selected according to the solubility of substances through a coupling-neutralizing-acidifying method.

Description

Technical Field

[0001] The present application relates to the technical field of preparation of sulfonic acid organic compounds, and in particular to a method for preparing 2-(N-morpholino)ethanesulfonic acid monohydrate. Background Art

[0002] 2-(N-Morpholino)ethanesulfonic acid monohydrate (MES) is a white powder at room temperature and is easily soluble in water. The sulfonic acid group in its molecular structure gives it a low dissociation constant, making it suitable for use in a wide pH range. Therefore, it is a common biological buffer salt and is widely used in many life science research fields such as ion exchange, protein electrophoresis, cell culture medium preparation, protein stability enhancement, and fluorescence microscopy.

[0003] At present, one of the processes for the synthesis of MES is to pass SO3 gas into ethanol, then add alkali and ether inhibitors to obtain sodium vinyl sulfonate, then couple it with morpholine to prepare the corresponding MES sodium salt, and finally obtain the corresponding product by ion exchange-crystallization. The raw materials of this method are relatively cheap, but SO3 itself is easy to react with water vapor to generate sulfuric acid, which is easy to corrode the corresponding equipment, indirectly increasing the investment cost of the equipment. In addition, the ion exchange process not only requires a large amount of ion exchange resin, but also generates a large amount of acidic waste liquid, which increases the cost of waste treatment.

[0004] Therefore, there is an urgent need to provide a new MES preparation method to overcome the above problems. Summary of the invention

[0005] The purpose of the present application is to provide a method for preparing 2-(N-morpholino)ethanesulfonic acid monohydrate to solve the above problems.

[0006] To achieve the above objectives, the present application provides a method for preparing 2-(N-morpholino)ethanesulfonic acid monohydrate, comprising:

[0007] Coupling: Mixing sodium 2-chloroethylsulfonate, water and morpholine for coupling reaction to obtain a coupling reaction product containing 2-(N-morpholino)ethanesulfonic acid sodium salt and hydrogen chloride;

[0008] Neutralization: mixing the coupling reaction product and the organic amine to conduct an acid-base neutralization reaction to obtain an acid-base neutralization reaction product;

[0009] Acidification: mixing the acid-base neutralization reaction product and the acid compound for acidification to obtain an acidified product;

[0010] Crystallization: Concentrating the acidified product to obtain a concentrated product, mixing the concentrated product with an organic solvent, and repeating the process for multiple times, filtering and drying the obtained solution to obtain 2-(N-morpholino)ethanesulfonic acid monohydrate.

[0011] The organic solvent includes one or more of ethanol, methanol, isopropanol, acetone, and acetonitrile.

[0012] Optionally, the molar ratio of the sodium 2-chloroethylsulfonate, the water, and the morpholine is 1:22-24:1.05-1.1.

[0013] Optionally, the preparation method of 2-(N-morpholino)ethanesulfonic acid monohydrate satisfies at least one of the following conditions:

[0014] A. the solution temperature of the sodium 2-chloroethylsulfonate, the water and the morpholine when mixed is less than or equal to 50° C.;

[0015] B. The coupling reaction temperature is 80°C-90°C and the reaction time is 4h-6h.

[0016] Optionally, the preparation method of 2-(N-morpholino)ethanesulfonic acid monohydrate satisfies at least one of the following conditions:

[0017] A. the solution temperature when the coupling reaction product and the organic amine are mixed is less than or equal to 40° C.;

[0018] B. the endpoint pH of the mixture of the coupling reaction product and the organic amine is greater than or equal to 7.5;

[0019] C. The organic amine includes one or more of triethylamine, diethylamine, ethylenediamine, ethanolamine, diethanolamine, and triethanolamine.

[0020] Optionally, the preparation method of 2-(N-morpholino)ethanesulfonic acid monohydrate satisfies at least one of the following conditions:

[0021] A. The solution temperature when the acid-base neutralization reaction product and the acid compound are mixed is 55°C-60°C;

[0022] B. the endpoint pH of the mixture of the acid-base neutralization reaction product and the acid compound is less than or equal to 5;

[0023] C. The acid compound includes organic acid and / or inorganic acid.

[0024] Optionally, the acidified product is subjected to a first concentration and a second concentration in sequence to obtain a first concentrated product and a second concentrated product, respectively.

[0025] Optionally, the temperature of the first concentration is 60° C.-65° C., and the vacuum degree is minus 0.095 MPa-minus 0.085 MPa;

[0026] The temperature of the second concentration is 40° C.-48° C., and the pressure vacuum degree is negative 0.095 MPa-negative 0.085 MPa.

[0027] Optionally, the preparation method of 2-(N-morpholino)ethanesulfonic acid monohydrate satisfies at least one of the following conditions:

[0028] A. the volume ratio of the first concentrated product to the organic solvent is 2:2.5-2.8;

[0029] B. the volume ratio of the first concentrated product to the second concentrated product is 2-2.3:1;

[0030] C. The volume ratio of the second concentrated product to the organic solvent is 1:3-3.2.

[0031] Optionally, purification is further performed after the filtration;

[0032] The purification includes: mixing the product obtained by filtration with dichloromethane.

[0033] Optionally, the drying temperature is 48°C-52°C.

[0034] Compared with the prior art, the beneficial effects of this application include:

[0035] The preparation method of 2-(N-morpholino)ethanesulfonic acid monohydrate provided by the present application, firstly, water is selected as the solvent of sodium 2-chloroethylsulfonate, which not only realizes a complete homogeneous reaction and reduces the solvent cost, but also avoids the problem that the solubility of sodium 2-chloroethylsulfonate is low due to the use of organic solvents, and the generated MES-Na salt is also insoluble in organic solvents, and will wrap the reactants so that the subsequent reaction cannot be carried out, thereby causing the problem of low reaction conversion rate; secondly, an organic amine is used instead of an inorganic base to neutralize the reaction system, so that the hydrochloric acid generated by the coupling reaction of sodium 2-chloroethylsulfonate and morpholine in the previous step is completely converted into an organic amine hydrochloride that is soluble in both water and organic solvents, thereby avoiding the subsequent reaction with MES free acid. The monohydrate precipitates from the solution together, which causes the difficulty of separation and purification; finally, since a large amount of organic amine hydrochloride and sodium acetate are generated in the organic amine neutralization-acid compound acidification step, as well as the presence of other unreacted substances, the water is not completely evaporated in the subsequent concentration and crystallization, but only partially evaporated, so that other substances except MES are retained in the solution, thereby improving the initial purity of the precipitated MES powder and reducing the material and energy consumption costs of subsequent further recrystallization; that is, the present application adopts simple and easily available basic raw materials, selects specific reagents according to the solubility of the substance through the coupling-neutralization-acidification method, and prepares 2-(N-morpholino)ethanesulfonic acid monohydrate. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings required for use in the embodiments will be briefly introduced below. It should be understood that the following drawings only show certain embodiments of the present application and therefore should not be regarded as limiting the scope of the present application.

[0037] Figure 1 This is the NMR image of 2-(N-morpholino)ethanesulfonic acid monohydrate prepared in Example 1. DETAILED DESCRIPTION

[0038] As used herein:

[0039] "Prepared from" is synonymous with "comprising." As used herein, the terms "comprising," "including," "having," "containing," or any other variation thereof, are intended to cover a non-exclusive inclusion. For example, a composition, process, method, article, or apparatus that comprises the listed elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, process, method, article, or apparatus.

[0040] The conjunction "consisting of excludes any unspecified element, step, or component. If used in a claim, this phrase renders the claim closed-ended so that it does not include materials other than those described, except for conventional impurities associated therewith. When the phrase "consisting of" appears in a clause of the body of a claim rather than immediately following the subject matter, it limits only the elements described in that clause; other elements are not excluded from the claim as a whole.

[0041] When an amount, concentration, or other value or parameter is expressed as a range, a preferred range, or a range defined by a series of upper preferred values ​​and lower preferred values, this should be understood as specifically disclosing all ranges formed by any pairing of any range upper limit or preferred value with any range lower limit or preferred value, regardless of whether the range is disclosed separately. For example, when a range of "1 to 5" is disclosed, the described range should be interpreted as including ranges "1 to 4", "1 to 3", "1 to 2", "1 to 2 and 4 to 5", "1 to 3 and 5", etc. When a numerical range is described in this article, unless otherwise stated, the range is intended to include its end values ​​and all integers and fractions within the range.

[0042] In these examples, parts and percentages are by mass unless otherwise indicated.

[0043] "Parts by mass" refers to the basic unit of measurement for expressing the mass ratio of multiple components. 1 part can represent any unit mass, such as 1g or 2.689g. If we say that the mass of component A is a parts and the mass of component B is b parts, it means the ratio of the mass of component A to the mass of component B is a:b. Alternatively, it means that the mass of component A is aK and the mass of component B is bK (K is an arbitrary number, indicating a multiple factor). It should not be misunderstood that, unlike the mass parts, the sum of the mass of all components is not limited to 100 parts.

[0044] "And / or" is used to indicate that one or both of the stated situations may occur, for example, A and / or B includes (A and B) and (A or B).

[0045] The present application provides a method for preparing 2-(N-morpholino)ethanesulfonic acid monohydrate, comprising:

[0046] Coupling: Mixing sodium 2-chloroethylsulfonate, water and morpholine for coupling reaction to obtain a coupling reaction product containing 2-(N-morpholino)ethanesulfonic acid sodium salt and hydrogen chloride;

[0047] Neutralization: mixing the coupling reaction product and the organic amine to conduct an acid-base neutralization reaction to obtain an acid-base neutralization reaction product;

[0048] Acidification: mixing the acid-base neutralization reaction product and the acid compound for acidification to obtain an acidified product;

[0049] Crystallization: Concentrating the acidified product to obtain a concentrated product, mixing the concentrated product with an organic solvent, and repeating the process for multiple times, filtering and drying the obtained solution to obtain 2-(N-morpholino)ethanesulfonic acid monohydrate.

[0050] It should be noted that directly concentrating the acidified product will result in a saturated solution rather than a solid. Only by adding it to an organic solvent and causing double solvent recrystallization can the corresponding 2-(N-morpholino)ethanesulfonic acid solid be produced.

[0051] The organic solvent includes one or more of ethanol, methanol, isopropanol, acetone and acetonitrile.

[0052] It should be noted that the principle of the above-mentioned organic solvents is that they must be miscible with water, otherwise the organic solvents will not be in sufficient contact with water, thereby reducing the crystallization efficiency.

[0053] In some embodiments, the molar ratio of the sodium 2-chloroethylsulfonate, the water, and the morpholine is 1:22-24:1.05-1.1.

[0054] Optionally, the molar ratio of sodium 2-chloroethylsulfonate, water and morpholine can be 1:22:1.05, 1:23:1.05, 1:24:1.05, 1:22:1.08, 1:22:1.1, 1:24:1.1 or any value between 1:22-24:1.05-1.1.

[0055] In some embodiments, the method for preparing 2-(N-morpholino)ethanesulfonic acid monohydrate satisfies at least one of the following conditions:

[0056] A. the solution temperature of the sodium 2-chloroethylsulfonate, the water and the morpholine when mixed is less than or equal to 50° C.;

[0057] Optionally, the solution temperature of the sodium 2-chloroethylsulfonate, the water and the morpholine when mixed can be 10°C, 20°C, 30°C, 40°C, 50°C or any value less than or equal to 50°C;

[0058] It should be noted that when the temperature of the solution mixture is less than or equal to 50° C., it can prevent the system from violently releasing heat and causing material splashing, and reduce the side reaction of morpholine ring opening.

[0059] B. The coupling reaction temperature is 80°C-90°C and the reaction time is 4h-6h.

[0060] Optionally, the temperature of the coupling reaction can be 80°C, 85°C, 90°C or any value between 80°C and 90°C, and the time can be 4h, 5h, 6h or any value between 4h and 6h.

[0061] In some embodiments, the method for preparing 2-(N-morpholino)ethanesulfonic acid monohydrate satisfies at least one of the following conditions:

[0062] A. the solution temperature when the coupling reaction product and the organic amine are mixed is less than or equal to 40° C.;

[0063] Optionally, the temperature of the solution when the coupling reaction product and the organic amine are mixed can be 10°C, 20°C, 30°C, 40°C, or any value less than or equal to 40°C;

[0064] B. the endpoint pH of the mixture of the coupling reaction product and the organic amine is greater than or equal to 7.5;

[0065] Optionally, the endpoint pH of the mixture of the coupling reaction product and the organic amine may be 7.5, 8, 8.5, 9, 9.5, 10, 11, 12 or any value greater than or equal to 7.5;

[0066] C. The organic amine includes one or more of triethylamine, diethylamine, ethylenediamine, ethanolamine, diethanolamine, and triethanolamine.

[0067] In some embodiments, the method for preparing 2-(N-morpholino)ethanesulfonic acid monohydrate satisfies at least one of the following conditions:

[0068] A. The solution temperature when the acid-base neutralization reaction product and the acid compound are mixed is 55°C-60°C;

[0069] Optionally, the temperature of the solution when the acid-base neutralization reaction product and the acid compound are mixed can be 55°C, 55°C, 57°C, 58°C, 59°C, 60°C or any value between 55°C and 60°C;

[0070] B. the endpoint pH of the third mixing is less than or equal to 5;

[0071] Optionally, the endpoint pH value of the mixture of the acid-base neutralization reaction product and the acid compound may be 1, 2, 3, 4, 5, or any value less than or equal to 5;

[0072] C. The acid compound includes organic acid and / or inorganic acid.

[0073] In some embodiments, the acidified product is subjected to a first concentration and a second concentration in sequence to obtain a first concentrated product and a second concentrated product, respectively. This can be understood as: the acidified product is subjected to a first concentration to obtain a first concentrated product, the first concentrated product is mixed with an organic solution to obtain a mixture, the mixture is subjected to a second concentration to obtain a second concentrated product, and the solution obtained by mixing the second concentrated product and the organic solution is filtered and dried to prepare 2-(N-morpholino)ethanesulfonic acid monohydrate.

[0074] The temperature of the first concentration is 60°C-65°C, and the vacuum degree is minus 0.095Mpa-minus 0.085Mpa;

[0075] Optionally, the temperature of the first concentration may be 60°C, 61°C, 62°C, 63°C, 64°C, 65°C or any value between 60°C and 65°C, and the vacuum degree may be negative 0.095 MPa, negative 0.09 MPa, negative 0.085 MPa or any value between negative 0.095 MPa and negative 0.085 MPa;

[0076] The temperature of the second concentration is 40° C.-48° C., and the vacuum degree is minus 0.095 MPa-minus 0.085 MPa.

[0077] Optionally, the temperature of the second concentration can be 40°C, 42°C, 44°C, 46°C, 48°C or any value between 40°C and 48°C, and the vacuum degree can be negative 0.095 MPa, negative 0.09 MPa, negative 0.085 MPa or any value between negative 0.095 MPa and negative 0.085 MPa.

[0078] In some embodiments, the method for preparing 2-(N-morpholino)ethanesulfonic acid monohydrate satisfies at least one of the following conditions:

[0079] A. the volume ratio of the first concentrated product to the organic solvent is 2:2.5-2.8;

[0080] Optionally, the volume ratio of the first concentrated product to the first organic solvent may be 2:2.5, 2:2.6, 2:2.7, 2:2.8 or any value between 2:2.5 and 2.8;

[0081] B. the volume ratio of the first concentrated product to the second concentrated product is 2-2.3:1;

[0082] Optionally, the volume ratio of the first concentrated product to the second concentrated product may be 2:1, 2.1:1, 2.2:1, 2.3:1 or any value between 2-2.3:1;

[0083] C. The volume ratio of the second concentrated product to the organic solvent is 1:3-3.2.

[0084] Optionally, the volume ratio of the second concentrated product to the organic solvent can be 1:3, 1:3.1, 1:3.2 or any value between 1:3-3.2.

[0085] In some embodiments, the filtration is followed by purification;

[0086] The purification includes: mixing the product obtained by filtration with dichloromethane.

[0087] It should be noted that dichloromethane can wash away impurities in the solid product, which are mainly incompletely reacted morpholine.

[0088] In some embodiments, the drying temperature is 48°C-52°C.

[0089] Optionally, the drying temperature may be 48°C, 49°C, 50°C, 51°C, 52°C or any value between 48°C and 52°C.

[0090] The embodiments of the present application will be described in detail below in conjunction with specific examples, but it will be appreciated by those skilled in the art that the following examples are only used to illustrate the present application and should not be considered as limiting the scope of the present application. If specific conditions are not specified in the examples, they are carried out according to normal conditions or the conditions recommended by the manufacturer. If the manufacturer is not specified for the reagents or instruments used, they are all conventional products that can be purchased commercially.

[0091] Example 1

[0092] This embodiment provides a method for preparing 2-(N-morpholino)ethanesulfonic acid monohydrate, and the specific steps are as follows:

[0093] S1, coupling: add 400mL of pure water to a 1L three-necked flask, then add 184.6g (1mol) of sodium 2-chloroethylsulfonate and dissolve it completely, then slowly drop 96mL (1.1mol) of morpholine into the three-necked flask, during this process, control the solution temperature T < 50°C, after all the dropwise addition is completed, adjust the reaction temperature to 80°C for 4h, after the reaction is completed, turn off the heating and adjust the temperature to room temperature 25°C;

[0094] S2, neutralization: at room temperature 25 ° C, slowly add excess triethylamine to the solution obtained in step S1, control the temperature T < 40 ° C, and stop adding when the pH of the solution is greater than 7.5;

[0095] S3, acidification: adjust the temperature of the solution obtained in step S2 to 55°C, then slowly add excess acetic acid dropwise to the above solution, stop adding dropwise when the pH of the solution is less than 5.0, turn off the heating, and adjust the temperature to room temperature 25°C;

[0096] S4, crystallization: at a temperature of 60 ° C, a vacuum degree of minus 0.09 MPa, the solution obtained in step S3 was concentrated once, and after being concentrated to a solution volume V1 of 200 mL, the solution was first cooled to room temperature of 25 ° C, and then 250 mL of ethanol was added. During this process, a large amount of solid was precipitated. The precipitated solid was filtered and then dissolved in water to form a solution. The solution was concentrated for a second time at a temperature of 40 ° C and a vacuum degree of minus 0.09 MPa. After being concentrated to a solution volume V2 of 100 mL, the solution temperature was also first cooled to room temperature of 25 ° C, and then 300 mL of ethanol was added to continue to precipitate a white solid. The final precipitated solid was filtered to obtain a filter cake;

[0097] S5. Purification: The filter cake obtained in step S4 was washed three times with dichloromethane and then dried at 50° C. to obtain 157.7 g of 2-(N-morpholino)ethanesulfonic acid monohydrate (MES).

[0098] The NMR of 2-(N-morpholino)ethanesulfonic acid monohydrate (MES) is as follows Figure 1 shown.

[0099] Example 2

[0100] The difference from Example 1 is that triethylamine is replaced by ethanolamine.

[0101] Example 3

[0102] The difference from Example 1 is that acetic acid is replaced by hydrochloric acid.

[0103] Comparative Example 1

[0104] The difference from Example 1 is that triethylamine is replaced by sodium hydroxide.

[0105] Comparative Example 2

[0106] The difference from Example 1 is that the first organic solvent is not added.

[0107] Comparative Example 3

[0108] The difference from Example 1 is that S2 and S3 are replaced in sequence.

[0109] Comparative Example 4

[0110] The difference from Example 1 is that the S2 neutralization step is not performed.

[0111] The conversion rate and purity of the 2-(N-morpholino)ethanesulfonic acid monohydrate prepared in the above examples and comparative examples were tested. The specific results are shown in Table 1.

[0112] Table 1 Conversion rate and purity detection

[0113] Experimental groups Weight / g Conversion rate / % purity / % Example 1 157.7 74 99.26 Example 2 142.8 67 99.30 Example 3 143.2 67.2 99.18 Comparative Example 1 127.8 60 93.25 Comparative Example 2 131.5 61.7 92.18 Comparative Example 3 139.8 65.6 97.25 Comparative Example 4 137.7 64.6 98.22

[0114] analyze:

[0115] As can be seen from Table 1, when Example 1 is used, the overall conversion rate is the highest, and the purity is usually >99%; while the conversion rates of other examples and comparative examples are all <70%, which may be due to the fact that in the process of adding acid or alkali to adjust the pH value of the solution, too much water-soluble salt is generated (mainly sodium hydroxide and sodium acetate), which is precipitated together with the free acid body in the subsequent crystallization process, thereby reducing the purity of the free acid body.

[0116] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present application, rather than to limit it. Although the present application has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present application.

[0117] In addition, those skilled in the art will appreciate that, although some embodiments herein include certain features included in other embodiments but not other features, the combination of features of different embodiments is meant to be within the scope of the present application and form different embodiments. For example, in the above claims, any one of the claimed embodiments may be used in any combination. The information disclosed in this background technology section is intended only to deepen the understanding of the overall background technology of the present application and should not be regarded as an admission or in any form of implication that the information constitutes prior art known to those skilled in the art.

Claims

1. A method for preparing 2-(N-morpholino)ethanesulfonic acid monohydrate, characterized in that: include: Coupling: Mixing sodium 2-chloroethylsulfonate, water and morpholine for coupling reaction to obtain a coupling reaction product containing 2-(N-morpholino)ethanesulfonic acid sodium salt and hydrogen chloride; Neutralization: mixing the coupling reaction product and the organic amine to conduct an acid-base neutralization reaction to obtain an acid-base neutralization reaction product; Acidification: mixing the acid-base neutralization reaction product and the acid compound for acidification to obtain an acidified product; Crystallization: Concentrating the acidified product to obtain a concentrated product, mixing the concentrated product with an organic solvent, and repeating the process for multiple times, filtering and drying the obtained solution to obtain 2-(N-morpholino)ethanesulfonic acid monohydrate.

2. The method for preparing 2-(N-morpholino)ethanesulfonic acid monohydrate according to claim 1, characterized in that: The molar ratio of the sodium 2-chloroethylsulfonate, the water and the morpholine is 1:22-24:1.05-1.

1.

3. The method for preparing 2-(N-morpholino)ethanesulfonic acid monohydrate according to claim 1, characterized in that: At least one of the following conditions is met: A. the solution temperature of the sodium 2-chloroethylsulfonate, the water and the morpholine when mixed is less than or equal to 50° C.; B. The coupling reaction temperature is 80°C-90°C and the reaction time is 4h-6h.

4. The method for preparing 2-(N-morpholino)ethanesulfonic acid monohydrate according to claim 1, characterized in that: At least one of the following conditions is met: A. the solution temperature when the coupling reaction product and the organic amine are mixed is less than or equal to 40° C.; B. the endpoint pH of the mixture of the coupling reaction product and the organic amine is greater than or equal to 7.5; C. the organic amine includes one or more of triethylamine, diethylamine, ethylenediamine, ethanolamine, diethanolamine, and triethanolamine; D. The organic solvent includes one or more of ethanol, methanol, isopropanol, acetone and acetonitrile.

5. The method for preparing 2-(N-morpholino)ethanesulfonic acid monohydrate according to claim 1, characterized in that: At least one of the following conditions is met: A. The solution temperature when the acid-base neutralization reaction product and the acid compound are mixed is 55°C-60°C; B. the endpoint pH of the mixture of the acid-base neutralization reaction product and the acid compound is less than or equal to 5; C. The acid compound includes organic acid and / or inorganic acid.

6. The method for preparing 2-(N-morpholino)ethanesulfonic acid monohydrate according to claim 1, characterized in that: The acidified product is sequentially subjected to a first concentration and a second concentration to obtain a first concentrated product and a second concentrated product, respectively.

7. The method for preparing 2-(N-morpholino)ethanesulfonic acid monohydrate according to claim 6, characterized in that: The temperature of the first concentration is 60°C-65°C, and the vacuum degree is -0.095Mpa--0.09Mpa; the temperature of the second concentration is 40°C-48°C, and the vacuum degree is -0.095Mpa--0.085Mpa.

8. The method for preparing 2-(N-morpholino)ethanesulfonic acid monohydrate according to claim 6, characterized in that: At least one of the following conditions is met: A. the volume ratio of the first concentrated product to the organic solvent is 2:2.5-2.8; B. the volume ratio of the first concentrated product to the second concentrated product is 2-2.3:1; C. The volume ratio of the second concentrated product to the organic solvent is 1:3-3.

2.

9. The method for preparing 2-(N-morpholino)ethanesulfonic acid monohydrate according to claim 1, characterized in that: Purification is also performed after the filtration; The purification comprises: mixing the product obtained by filtration with dichloromethane.

10. The method for preparing 2-(N-morpholino)ethanesulfonic acid monohydrate according to any one of claims 1 to 9, characterized in that: The drying temperature is 48°C-52°C.

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