Synthesis of 4-aminosulfonylbutyric acid

Abstract

This invention relates to the field of organic synthesis technology, and more specifically, to a method for synthesizing 4-aminosulfonylbutyric acid, which is carried out according to the following synthetic route: the raw materials are simple and readily available, the synthesis cost is low, the synthesis steps are simple, the yield is high, and it is easy to achieve industrial mass production.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of organic synthesis, in particular to a synthesis method of 4-aminosulfonyl butyric acid. BACKGROUND

[0002] Somapacitan (Sogroya) is a novel, reversible, albumin-bound human growth hormone derivative that is modified from native hGH to enhance its binding to endogenous plasma proteins, white proteins, thereby prolonging the molecule's half-life. The introduction of the unnatural amino acid 4-aminosulfonyl butyric acid into therapeutic proteins through acylation facilitates the binding of these molecules to circulating albumin. In humans, the non-covalent binding of the molecule to albumin in the blood increases the molecular weight of the product, avoids rapid renal clearance and prevents metabolic degradation, and greatly prolongs the half-life in the body. The fatty acid side chain with non-covalent albumin binding properties in somapacitan makes it possible to be administered subcutaneously once a week.

[0003] It can be seen that 4-aminosulfonyl butyric acid plays an important role in the efficacy of Sogroya, and the synthesis of 4-aminosulfonyl butyric acid reported in the prior art has a complex synthesis process, difficult to implement synthesis conditions and serious pollution.

[0004] In view of this, the present application is proposed. SUMMARY

[0005] The purpose of the present application is to provide a synthesis method of 4-aminosulfonyl butyric acid. The synthesis method provided by the embodiments of the present application is simple to operate and has a short process flow route.

[0006] The present application is implemented as follows:

[0007] In a first aspect, the present application provides a synthesis method of 4-aminosulfonyl butyric acid, which is synthesized by referring to the following synthesis path:

[0008]

[0009] In an optional embodiment, the step of forming compound A comprises mixing 4-bromobutyric acid, a disulfide salt and an organic solvent and hydrolyzing in a base.

[0010] In an optional embodiment, the organic solvent is selected from ketone solvents, nitrile solvents or amide solvents, preferably acetone, DMF or acetonitrile, more preferably acetone;

[0011] Preferably, the base is selected from carbonates or bicarbonates; more preferably sodium bicarbonate, sodium carbonate or potassium carbonate; more preferably sodium bicarbonate;

[0012] More preferably, the molar ratio of the 4-bromobutyric acid, the organic solvent and the base is 1:(1-1.3):(2-6); preferably 1:1.1:4.

[0013] More preferably, the reaction temperature is 30-70℃ and the reaction time is 1-4h, more preferably the reaction temperature is 60℃ and the time is 2.5h.

[0014] In an alternative embodiment, the step of forming compound B comprises mixing compound A and a condensing agent to perform a condensation reaction.

[0015] Preferably, it comprises mixing the compound A, ethanol and a condensing agent to perform a condensation reaction.

[0016] In an alternative embodiment, the condensing agent is selected from at least one of DIC, EDC, DCC, DMAP and thionyl chloride.

[0017] Preferably, the molar ratio of the compound A, the ethanol and the condensing agent is 1:1-1.3:1-1.3.

[0018] The reaction temperature is -10 to 30℃ and the time is 2-6h.

[0019] In an alternative embodiment, the step of forming compound C comprises mixing compound B, a catalyst and an oxidizing agent to perform a reaction.

[0020] In an alternative embodiment, the catalyst is selected from nitrates, preferably potassium nitrate.

[0021] Preferably, the oxidizing agent is selected from any one of oxaziridines and chlorine gas, preferably oxaziridines.

[0022] Preferably, the molar ratio of the compound B, the catalyst and the oxidizing agent is 1:2-5:2-5.

[0023] Preferably, the reaction temperature is -10 to 10℃ and the time is 6-20h.

[0024] In an alternative embodiment, the step of forming compound D comprises mixing compound C, an organic solvent and an ammonia-like substance to perform a reaction.

[0025] In an alternative embodiment, the organic solvent is selected from at least one of ester solvents, chloroalkane solvents, furan solvents, nitrile solvents and amide solvents.

[0026] Preferably, the organic solvent is selected from at least one of EA, DCM, THF, DMF, acetonitrile, dichloromethane and chloroform.

[0027] Preferably, the ammonia-like substance is selected from ammonia gas or ammonia water.

[0028] Preferably, the molar ratio of the compound C and the ammonia-like substance is 1:2-5.

[0029] Preferably, the reaction temperature is -10 to 10℃.

[0030] In an alternative embodiment, the step of forming the compound E comprises hydrolyzing the compound D under basic conditions.

[0031] Preferably, the base forming the basic conditions is selected from hydroxides, preferably at least one of lithium hydroxide, sodium hydroxide, potassium hydroxide and barium hydroxide.

[0032] Preferably, the molar ratio of the compound D and the base is 1:1-1.3.

[0033] The present application has the following beneficial effects: the synthesis method of 4-aminosulfonyl butyric acid provided by the embodiments of the present application has simple and readily available raw materials, low synthesis cost, simple synthesis steps, high yield and easy industrial production. BRIEF DESCRIPTION OF DRAWINGS

[0034] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the following will briefly introduce the drawings needed to be used in the embodiments. It should be understood that the following drawings only show some embodiments of the present application, and therefore should not be regarded as a limitation on the scope. For those skilled in the art, other related drawings can also be obtained without creative labor on the basis of these drawings.

[0035] Figure 1 The nuclear magnetic hydrogen spectrum of 4-aminosulfonyl butyric acid provided by Embodiment 1 of the present application. DETAILED DESCRIPTION

[0036] In order to make the purpose, technical solutions and advantages of the embodiments of the present application more clear, the technical solutions in the embodiments of the present application will be described clearly and completely below. The specific conditions not mentioned in the embodiments are carried out according to the conventional conditions or the conditions suggested by the manufacturers. The reagents or instruments not mentioned by the manufacturers are all conventional products that can be purchased in the market.

[0037] The embodiments of the present application provide a synthesis method of 4-aminosulfonyl butyric acid, which is synthesized by referring to the following synthesis path:

[0038]

[0039] The specific process is as follows:

[0040] (1) formation of compound A;

[0041] 4-bromobutyric acid, a disulfide salt (for example, including but not limited to sodium disulfide) and an organic solvent are mixed and hydrolyzed in a base. Specifically, 4-bromobutyric acid is heated with a disulfide salt in an organic solvent, and then hydrolyzed in a base.

[0042] wherein the organic solvent is selected from a ketone solvent, a nitrile solvent or an amide solvent, preferably acetone, DMF or acetonitrile, more preferably acetone; the base is selected from a carbonate or a bicarbonate; more preferably sodium bicarbonate, sodium carbonate or potassium carbonate; more preferably sodium bicarbonate.

[0043] Further, the molar ratio of 4-bromobutyric acid, the organic solvent and the base is 1:(1-1.3):(2-6); for example, any value between 1:(1-1.3):(2-6) such as 1:1:2, 1:1.2:3, 1:1.3:3, 1:1.2:5, 1:1.1:4 and 1:1.2:6, preferably 1:1.1:4. Specifically, for example, the molar ratio of 4-bromobutyric acid, acetone, sodium bicarbonate is 1:(1-1.3):(2-6), preferably 1:1.1:4.

[0044] Further, the reaction temperature is 30-70℃, for example, any value between 30-70℃ such as 30℃, 40℃, 50℃, 60℃ and 70℃; the reaction time is 1-4h, for example, any value between 1-4h such as 1h, 2h, 3h and 4h. More preferably, the reaction temperature is 60℃ and the time is 2.5h.

[0045] After the reaction is completed, the reaction system is post-treated, for example, acid is adjusted, extracted, washed, dried and concentrated to obtain compound A.

[0046] (2) synthesis of compound B;

[0047] Compound A and a condensing agent are mixed to perform a condensation reaction; specifically, the compound A, ethanol and a condensing agent are mixed to perform a condensation reaction.

[0048] wherein the condensing agent is selected from at least one of DIC, EDC (or a salt thereof, for example, EDC.HCL), DCC, DMAP and thionyl chloride; it can also be a combination of any two, any three or even any four of the above DIC, EDC, DCC, DMAP and thionyl chloride.

[0049] The molar ratio of compound A, the ethanol and the condensing agent is 1:1-1.3:1-1.3; for example, it can be 1:1:1, 1:1.2:1.3, 1:1:1.2, 1:1.1:1.2, 1:1.1:1.3, 1:1.2:1.1, 1:1.2:1.3, 1:1.3:1.1, 1:1.3:1 and 1:1.3:1.3, etc. between 1:1-1.3:1-1.3, preferably 1:1.05:1. For example, the molar ratio of compound A, ethanol, EDC.HCL is 1:1-1.3:1-1.3:1-1.5, and the best is 1:1.05:1:1.2.

[0050] Further, the reaction temperature is -10 to 30℃, for example, -10℃, 15℃, 20℃, 25℃ and 30℃, etc. between -10 to 30℃ of any value. The time is 2-6 hours, for example, 2 hours, 3 hours, 4 hours, 5 hours and 6 hours, etc. between 2-6 hours of any value. The preferred temperature is 25℃, and the time is 4 hours.

[0051] After the reaction, the reaction system is post-treated, for example, washed with water, dried, filtered and concentrated.

[0052] (3) formation of compound C;

[0053] Compound B, a catalyst and an oxidant are mixed for reaction; specifically, compound B, a solvent, a catalyst and an oxidant are mixed for reaction.

[0054] The solvent is selected from nitrile solvents, including but not limited to acetonitrile. The catalyst is selected from nitrate, preferably potassium nitrate; the oxidant is selected from any one of oxaziridines, chlorine, preferably oxaziridines.

[0055] Further, the molar ratio of compound B, the catalyst and the oxidant is 1:2-5:2-5; for example, 1:2:3, 1:2:5, 1:3:3, 1:4:5, 1:3:3, 1:5:2, 1:4:2, 1:3:1, 1:4:4 and 1:2:1, etc. between 1:2-5:2-5 of any value. For example, the molar ratio of compound B, potassium nitrate and oxaziridines is 1:2-5:2-5; the best is 1:3:3.

[0056] Further, the reaction temperature is -10 to 10℃, for example, -10℃, -5℃, 0℃, 5℃ and 10℃, etc. between -10 to 10℃ of any value; preferably 0℃. The time is 6-20h, for example, 6h, 7h, 8h, 9h and 20h, etc. between 6-20h of any value, and the best is 8h.

[0057] (4) formation of compound D;

[0058] The compound C, an organic solvent and an ammonia-like substance are mixed to react.

[0059] The organic solvent is selected from at least one of ester solvents, chloroalkane solvents, furan solvents, nitrile solvents and amide solvents; preferably, the organic solvent is ethyl acetate (EA), dichloromethane (DCM), tetrahydrofuran (THF), acetonitrile, DMF, dichloromethane, chloroform, or any mixture of any of them in any proportion, preferably ethyl acetate.

[0060] The ammonia-like substance can be selected from aqueous ammonia or ammonia gas, preferably aqueous ammonia.

[0061] The molar ratio of the compound C to the ammonia-like substance is 1:2-5; for example, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, or any value between 1:2 and 1:5. The reaction temperature is -10 to 10°C, for example, -10°C, -5°C, 0°C, 5°C, 10°C, or any value between -10 and 10°C. Preferably, 0°C.

[0062] After the reaction is completed, the reaction system is post-processed, for example, extracted, dried, concentrated, crystallized, filtered and dried.

[0063] (5) formation of compound E;

[0064] Compound D is hydrolyzed under alkaline conditions; the base forming the alkaline conditions is selected from hydroxides, preferably at least one of lithium hydroxide, sodium hydroxide, potassium hydroxide and barium hydroxide;

[0065] The above hydroxides can be hydrates or non-hydrates, for example, barium hydroxide can be barium hydroxide octahydrate.

[0066] The organic solvent used in the above hydrolysis process can be selected from any one of tetrahydrofuran, furan solvents, methanol, monohydric alcohol solvents and water, or at least two combinations, preferably tetrahydrofuran.

[0067] The molar ratio of the compound D to the base is 1:1-1.3; for example, 1:1, 1:1.1, 1:1.2, 1:1.3, or any value between 1:1 and 1:1.3, preferably 1:1.05. The reaction time is 1-4h, for example, 1h, 2h, 3h, 4h, or any value between 1h and 4h, preferably 2h.

[0068] After the reaction is completed, the reaction system is post-processed, for example, the pH of the reaction system is adjusted to 4-5 using dilute hydrochloric acid aqueous solution (for example, 4N HCl), and then concentrated, the concentrate is washed with methanol, the organic phase is collected by filtration, concentrated to dryness, crystallized and dried to obtain compound E.

[0069] It should be noted that the reaction time of each step provided by the embodiments of the present application, or the step without providing the reaction time, is actually ended until a certain reaction raw material is ended by TCL monitoring.

[0070] The features and performances of the present application are further described in detail below in combination with the embodiments.

[0071] Embodiment 1

[0072] The present embodiment provides a synthesis method of 4-aminosulfonyl butyric acid, comprising:

[0073]

[0074] Formation of compound A: 595 g of 4-bromobutyric acid is stirred into 2.2 L of acetone, and then 427 g of sodium disulfide, sodium bicarbonate is added, and reacted at 60°C for 2.5 h. The reaction solution is cooled to 20°C, and then added into 5 L of water, 4 L of EA is added, and then 4 mol / L of HCl is added under stirring, and then separated, and then the aqueous phase is extracted with EA twice, and then the EA phases are combined, and then the combined EA phase is washed with saturated brine once, and then concentrated under reduced pressure at 50°C, to obtain 380 g of liquid 4-mercaptobutyric acid, with a yield of 88.9%.

[0075]

[0076] Formation of compound B: 250 g of intermediate 4,4'-dithiodibutyric acid is stirred into DCM, and then anhydrous EtOH is added, and then cooled to <5°C in an ice-salt bath, and then EDCI and DMAP are added, and then reacted for 4 h. The reaction solution is washed with 1 mol / L of HCl twice, and then washed with saturated brine once, and then dried, filtered, and concentrated, and then concentrated to obtain 310 g of liquid diethyl 4,4'-dithiodibutyrate, with a yield of 100%.

[0077]

[0078] Formation of compound C: 310 g of diethyl 4,4'-dithiodibutyrate is added into CH3CN, and then 325 g of KNO3 is added, and then cooled to <5°C in an ice-salt bath, and then 256 ml of SO2Cl2 is added dropwise, and then reacted for 10 h after the dropwise addition is completed. The reaction solution is concentrated to obtain 350 g of compound C, with a yield of 80.4%.

[0079]

[0080] Formation of compound D: after the intermediate C is dissolved in EEA, the temperature is cooled to <5°C in an ice-salt bath, and then 56 ml of ammonia water is added dropwise, and then reacted for 0.5 h after the dropwise addition is completed, and then separated, and then the EA phase is dried, and then concentrated under reduced pressure at 50°C, and then crystallized with petroleum ether, and then filtered, and then dried to obtain 178 g of solid, with a yield of 86%.

[0081]

[0082] Formation of compound E: 178 g of ethyl 4-aminosulfonyl butyrate was dissolved in 1 L of tetrahydrofuran, 250 mL of 4N sodium hydroxide was added, and the reaction was carried out for 2 h. The reaction solution was adjusted to Ph = 4 with 4N hydrochloric acid, and concentrated under reduced pressure to obtain a solid. The solid was dissolved in methanol, filtered, and the filtrate was concentrated under reduced pressure to obtain 142 g of 4-aminosulfonyl butyric acid, with a yield of 95%.

[0083] The results of the characterization of the product are shown in Table 1 Figure 1 , and the specific characterization data are as follows: 1 H NMR (400 MHz, DMSO-d6) δ 12.13 (s, 1H), 6.75 (s, 2H), 3.00-2.91 (m, 2H), 2.35 (t, J = 7.4 Hz, 2H), 1.92-1.79 (m, 2H).

[0084] Example 2

[0085] This example provides a method for synthesizing 4-aminosulfonyl butyric acid. The specific method is as in Example 1, except that the formation of compound A is different.

[0086] Specifically, as follows: Formation of compound A: 595 g of 4-bromobutyric acid was stirred into 1.2 L of DMF, and then 427 g of sodium disulfide, sodium bicarbonate was added, and the reaction was carried out at 30°C for 2.5 h. The reaction solution was cooled to 20°C, and then added to 5 L of water, 4 L of EA was added, and then 4 mol / L of HCl was added with stirring, and then the liquid was separated, the aqueous phase was extracted twice with EA, and then the combined EA phase was washed once with saturated brine, and then concentrated under reduced pressure at 50°C to obtain 324.4 g of 4-mercaptobutyric acid as a liquid, with a yield of 75.9%.

[0087] Example 3

[0088] This example provides a method for synthesizing 4-aminosulfonyl butyric acid. The specific method is as in Example 1, except that the formation of compound B is different.

[0089] Specifically, as follows: Formation of compound B: 180 g of intermediate 4, 4'-dithiodibutyric acid was stirred into anhydrous EtOH, and then cooled to <0°C in an ice-salt bath, and then added with thionyl chloride, and then the reaction was carried out for 4 h. After the concentration was completed, 182 g of diethyl 4, 4'-dithiodibutyrate was obtained as a liquid, with a yield of 89%.

[0090] Example 4

[0091] This example provides a method for synthesizing 4-aminosulfonyl butyric acid. The specific method is as in Example 1, except that the formation of compound C is different.

[0092] Specifically as follows: formation of compound C: 310 g of diethyl 4,4'-dithiodiphenylate was added to CH3CN, then 325 g of KNO3 was added, and the reaction was cooled to <5°C in an ice-salt bath, then Cl2 was introduced, and after the introduction was completed, the reaction was allowed to proceed for 5 h. The reaction solution was concentrated to obtain 326.4 g of intermediate C at a yield of 75%.

[0093] Example 5

[0094] This example provides a method for synthesizing 4-aminosulfonyl butyric acid, and the specific method is as in Example 1, except that the formation of compound D is different.

[0095] Specifically as follows: formation of compound D: 148 g of intermediate C was dissolved in DMF, and the solution was cooled to <5°C in an ice-salt bath, then 56 ml of ammonia water was added, and after the addition was completed, the reaction was allowed to proceed for 0.5 h, then water was added to quench the reaction, the EA was extracted and separated, the EA phase was dried, and concentrated under reduced pressure at 50°C, then the product was crystallized from petroleum ether, filtered, and dried to obtain 110.5 g of a solid at a yield of 73.4%.

[0096] Example 6

[0097] This example provides a method for synthesizing 4-aminosulfonyl butyric acid, and the specific method is as in Example 1, except that the formation of compound E is different.

[0098] Specifically as follows: formation of compound E: 78 g of ethyl 4-aminosulfonyl butyrate was dissolved in 1 L of tetrahydrofuran, then 250 ml of 4N lithium hydroxide was added, and the reaction was allowed to proceed for 2 h. The reaction solution was adjusted to Ph = 4 with 4N hydrochloric acid, and concentrated under reduced pressure to obtain a solid, which was dissolved in methanol, filtered, and the filtrate was concentrated under reduced pressure to obtain 63.4 g of 4-aminosulfonyl butyric acid at a yield of 95%.

[0099] Comparative Example 1

[0100] The comparative example provides the operation of forming compound A: 59.5 g of 4-bromobutyric acid is stirred into 33 mL of anhydrous ethanol, and 29.5 g of thiourea is added, and the reaction is refluxed at 80°C for 2.5 h. The reaction solution is cooled to 20°C, and 500 mL of an aqueous NaOH solution is added under an ice-salt bath, and the reaction is continued to be refluxed at 80°C for 4 h. The reaction solution is filtered, and the solid is added into 4 L of EA, and 4 mol / L HCl is added under stirring until the solid is dissolved, and the liquid is separated, and the aqueous phase is extracted with EA twice, and then the EA phases are combined, and the combined EA phase is washed with saturated brine once, and then it is concentrated under reduced pressure at 50°C to obtain 19.0 g of liquid 4-mercaptobutyric acid. 19.0 g of 4-mercaptobutyric acid is stirred into 1.5 L of EA, and NaI is added, and the temperature is cooled to <5°C under an ice-salt bath, and 30% H2O2 is added dropwise, and the reaction is continued for 10 h. The reaction solution is washed with a saturated Na2S2O3 solution twice, and then it is dried and filtered, and concentrated at 45°C to obtain 8.5 g of solid 4,4'-dithiodibutyric acid, with a yield of 44.8%.

[0101] It can be seen that the yield of compound A is significantly reduced by changing the synthetic route provided by the embodiment of the present application.

[0102] Comparative Example 2

[0103] The comparative example provides the operation of forming compound C: 310 g of diethyl 4,4'-dithiodibutyrate is added into a mixture of ether and water. Cl2 gas is introduced into the reaction bottle and stirred vigorously for 5 hours. The chlorine is introduced at a slow speed. N2 gas is bubbled through the solution for 1 hour to remove excess Cl2, and the reaction solution is extracted with CH2Cl2 (2 x 100 mL), dried with Na2SO4, and concentrated to obtain 52.5 g with a yield of 12.06%.

[0104] It can be seen that the yield of the product is significantly reduced by changing the conditions of the embodiment of the present application.

[0105] Comparative Example 3

[0106] The comparative example provides the operation of forming compound C: 31 g of diethyl 4,4'-dithiodibutyrate is added into CH3CN, and 325 g of KI is added, and the temperature is cooled to <5°C under an ice-salt bath, and 256 mL of SO2Cl2 is added dropwise, and the reaction is continued for 10 h after the dropwise addition is completed. The reaction solution is concentrated to obtain compound C, 3.5 g with a yield of 8.4%.

[0107] The above only describes the preferred embodiments of the present application and is not intended to limit the present application. Various modifications and changes can be made by those skilled in the art based on the present application. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. A method for the synthesis of 4-aminosulfonyl butyric acid, characterized by, The synthesis is carried out with reference to the following synthesis path: wherein the step of forming Compound A comprises mixing 4-bromobutyric acid, a disulfide salt, and an organic solvent and performing hydrolysis in a base; The step of forming compound B comprises: mixing compound A and condensing agent for condensation reaction; The step of forming compound C comprises: mixing compound B, catalyst and oxidizing agent for reaction; wherein, the catalyst is selected from potassium nitrate; the oxidizing agent is selected from sulfone dichloride; the molar ratio of the compound B, the catalyst and the oxidizing agent is 1:2-5:2-5; the reaction temperature is-10 to 10℃, and the reaction time is 6-20h; the solvent is selected from nitrile solvent; the step of forming compound D comprises: mixing compound C, organic solvent and ammonia substance for reaction; the ammonia substance is selected from ammonia gas or ammonia water; The step of forming compound E comprises: hydrolyzing compound D under alkaline condition.

2. The method of claim 1, wherein the 4-aminosulfonyl butyric acid is synthesized by the following reaction scheme: ###0001### 2 The conditions of forming compound A comprise: the organic solvent is selected from ketone solvent, nitrile solvent or amide solvent; The base is selected from carbonate or bicarbonate; The molar ratio of the 4-bromobutyric acid, the organic solvent and the base is 1: (1-1.3): (2-6); The reaction temperature is 30-70℃, and the reaction time is 1-4h.

3. The method of synthesis of 4-aminosulfonyl butyric acid according to claim 2, characterized by, The conditions of forming compound A comprise: the organic solvent is acetone, DMF or acetonitrile; The base is sodium bicarbonate, sodium carbonate or potassium carbonate; The molar ratio of the 4-bromobutyric acid, the organic solvent and the base is 1:1.1:4; The reaction temperature is 60℃, and the time is 2.5h.

4. The method for synthesizing 4-aminosulfonyl butyric acid according to claim 1, wherein The step of forming compound B comprises: mixing compound A, ethanol and condensing agent for condensation reaction.

5. The method for synthesizing 4-aminosulfonylbutyric acid according to claim 4, characterized in that, The conditions of forming compound B comprise: the condensing agent is selected from at least one of DIC, EDC, DCC, DMAP and sulfurous chloride; The molar ratio of the compound A, the ethanol and the condensing agent is 1:1-1.3:1-1.3; The reaction temperature is-10 to 30℃, and the time is 2-6h.

6. The method for synthesizing 4-aminosulfonylbutyric acid according to claim 1, characterized in that, The conditions of forming compound D comprise: the organic solvent is selected from at least one of ester solvent, chloroalkane solvent, furan solvent, nitrile solvent and amide solvent; The molar ratio of the compound C and the ammonia substance is 1:2-5; The reaction temperature is-10 to 10℃.

7. The method of synthesis of 4-aminosulfonyl butyric acid as claimed in claim 1, wherein, The conditions of forming compound D comprise: the organic solvent is selected from at least one of EA, DCM, THF, DMF, acetonitrile, dichloromethane and chloroform. ​ 8. The method for synthesizing 4-aminosulfonylbutyric acid according to claim 1, characterized in that, The conditions of forming compound E comprise: The base for forming the alkaline condition is selected from hydroxide, The molar ratio of the compound D and the base is 1:1-1.

3.

9. The method for synthesizing 4-aminosulfonylbutyric acid according to claim 1, characterized in that, The conditions of forming compound E comprise: the base for forming the alkaline condition is selected from at least one of lithium hydroxide, sodium hydroxide, potassium hydroxide and barium hydroxide.

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