Preparation method of 3-[3-(cholamidopropyl) dimethylamino] propanesulfonic acid inner salt

Abstract

The invention belongs to the technical field of compounds, and discloses a preparation method of 3-[3-(cholamidopropyl) dimethylamino] propanesulfonic acid inner salt, which comprises the following steps: S1, carrying out reflux reaction on cholic acid and p-toluenesulfonic acid in a methanol solvent, cooling, crystallizing, filtering, and drying to obtain a product I; s2, heating the product I, N, N-dimethyl-1, 3-diaminopropane and p-toluenesulfonic acid to react for a certain time, evaporating to be thick after the reaction, adding water to crystallize, filtering, and drying to obtain cholamide; s3, carrying out reflux reaction on cholanamide and 1, 3-dichloropropane in ethanol, and carrying out reduced pressure distillation until the product is thick, so as to obtain a product III; and S4, adding water, sodium sulfite and copper chloride into the product III, carrying out reflux reaction for a certain time, carrying out desalting treatment, then carrying out evaporative crystallization, filtering and drying to obtain the 3-[3-(cholamidopropyl) dimethylamino] propanesulfonic acid inner salt. The method disclosed by the invention has the beneficial effects that only water and ethanol are used as solvents, so that the use of DMF (Dimethyl Formamide) is avoided.

Description

Technical Field

[0001] This invention relates to the field of compound technology, and in particular to a method for preparing the inner salt of 3-[3-(cholamidopropyl)dimethylamino]propanesulfonic acid. Background Technology

[0002] CHAPS, short for 3-[3-(cholamidopropyl)dimethylamino]propanesulfonic acid inner salt, is a non-denaturing zwitterionic detergent used in membrane biochemistry to dissolve membrane proteins and disrupt protein-protein interactions. However, almost all commercially available CHAPS products contain DMF residues, which limits their use in some areas.

[0003] Therefore, it is necessary to provide a method for preparing the inner salt of 3-[3-(cholamidopropyl)dimethylamino]propanesulfonic acid to avoid the use of DMF and to make the product purer and have a higher yield. Summary of the Invention

[0004] This invention discloses a method for preparing the inner salt of 3-[3-(cholanamidopropyl)dimethylamino]propanesulfonic acid, which can effectively solve the technical problems involved in the background art.

[0005] To achieve the above object, the technical solution of the present invention is: A method for preparing an inner salt of 3-[3-(cholamidopropyl)dimethylamino]propanesulfonic acid includes the following steps: S1, cholic acid and p-toluenesulfonic acid were refluxed in methanol solvent, cooled, crystallized, filtered, and then dried to obtain product one; S2, Product 1, N,N-dimethyl-1,3-diaminopropane and p-toluenesulfonic acid were heated and reacted for a certain time. After the reaction, the mixture was evaporated to a thick consistency, added to water to crystallize, filtered and dried to obtain cholanamide. S3, choline, and 1,3-dichloropropane were refluxed in ethanol and distilled under reduced pressure until viscous to obtain product three. S4. Water, sodium sulfite, and copper chloride were added to product three, and the mixture was refluxed for a certain period of time to perform desalting treatment. Subsequently, the product was evaporated and crystallized, filtered, and dried to obtain 3-[3-(cholamidopropyl)dimethylamino]propanesulfonic acid inner salt.

[0006] As a preferred improvement of the present invention: in step S1, after filtration, methanol is concentrated and crystallized to obtain solid one, solid one is dried to obtain product two, and product two is added to product one.

[0007] As a preferred improvement of the present invention: in step S1, 100g of cholic acid, 250ml of methanol, and 1g of p-toluenesulfonic acid are refluxed for 2 hours.

[0008] As a preferred improvement of the present invention: in step S1, drying is performed at 40-60°C.

[0009] As a preferred improvement of the present invention: in step S2, 100g of methyl cholate, 100ml of N,N-dimethyl-1,3-diaminopropane and 1g of p-toluenesulfonic acid are heated to 120 degrees and reacted for 16 hours.

[0010] As a preferred improvement of the present invention: in step S2, drying is performed at 60-80°C.

[0011] As a preferred improvement of the present invention: in step S3, 100g of cholineamide, 200ml of ethanol and 25g of 1,3-dichloropropane are refluxed for 6 hours.

[0012] As a preferred improvement of the present invention: in step S4, 200ml of water, 30g of sodium sulfite and 1g of copper chloride are added, and the mixture is refluxed for 10 hours.

[0013] As a preferred improvement of the present invention: in step S4, desalination is performed by an electrodialysis device.

[0014] As a preferred improvement of the present invention: in step S4, drying is performed at 65-75°C.

[0015] The beneficial effects of the present invention are as follows: This invention abandons the sulfonation reaction using propane sulfonyl lactone and uses an alternative route, thus requiring only water and ethanol as solvents and avoiding the use of DMF. The inner salt of 3-[3-(cholamidopropyl)dimethylamino]propanesulfonic acid is obtained through a four-step reaction, with high product purity and high yield. Attached Figure Description

[0016] To more clearly illustrate the technical solutions in the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort, wherein: Figure 1 This is reaction process one of the present invention; Figure 2 This is reaction process two of the present invention; Figure 3 This is reaction process three of the present invention; Figure 4 This is reaction process four of the present invention. Detailed Implementation

[0017] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0018] It should be noted that all directional indications (such as up, down, left, right, front, back, etc.) in the embodiments of the present invention are only used to explain the relative positional relationship and movement of each component in a certain specific posture (as shown in the figure). If the specific posture changes, the directional indication will also change accordingly.

[0019] Furthermore, in this invention, descriptions involving "first," "second," etc., are for descriptive purposes only and should not be construed as indicating or implying their relative importance or implicitly specifying the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include at least one of that feature. In the description of this invention, "a plurality of" means at least two, such as two, three, etc., unless otherwise explicitly specified.

[0020] In this invention, unless otherwise explicitly specified and limited, the terms "connection," "fixed," etc., should be interpreted broadly. For example, "fixed" can mean a fixed connection, a detachable connection, or an integral part; it can mean a mechanical connection or an electrical connection; it can mean a direct connection or an indirect connection through an intermediate medium; it can mean the internal communication of two components or the interaction between two components, unless otherwise explicitly limited. Those skilled in the art can understand the specific meaning of the above terms in this invention according to the specific circumstances.

[0021] Furthermore, the technical solutions of the various embodiments of the present invention can be combined with each other, but only if they are feasible for those skilled in the art. If the combination of technical solutions is contradictory or cannot be implemented, it should be considered that such combination of technical solutions does not exist and is not within the scope of protection claimed by the present invention.

[0022] This invention provides a method for preparing the inner salt of 3-[3-(cholanamidopropyl)dimethylamino]propanesulfonic acid, comprising the following steps: S1, cholic acid and p-toluenesulfonic acid are refluxed in methanol solvent, cooled, crystallized, filtered, and then dried to obtain product one ( Figure 1 S2, Product 1, N,N-dimethyl-1,3-diaminopropane and p-toluenesulfonic acid were heated and reacted for a certain time. After the reaction, the mixture was evaporated to a thick consistency, crystals were added to water to precipitate, filtered, and dried to obtain cholanamide. Figure 2S3, choline, and 1,3-dichloropropane were refluxed in ethanol and distilled under reduced pressure until viscous to give product tri( Figure 3 S4, water, sodium sulfite, and copper chloride were added to product three, and the mixture was refluxed for a certain time to perform desalting treatment. Then, it was evaporated and crystallized, filtered, and dried to obtain 3-[3-(cholamidopropyl)dimethylamino]propanesulfonic acid inner salt ( Figure 4 ).

[0023] In this embodiment, in step S1, after filtration, methanol is concentrated and crystallized to obtain solid one. Solid one is dried to obtain product two, which is then added to product one. In step S1, 100g of cholic acid, 250ml of methanol, and 1g of p-toluenesulfonic acid are refluxed for 2 hours. In step S1, drying is performed at 40-60℃, preferably 50℃. In step S2, 100g of methyl cholate, 100ml of N,N-dimethyl-1,3-diaminopropane, and 1g of p-toluenesulfonic acid are heated to 120℃ and reacted for 16 hours. In step S2, drying is performed at 60-80℃, preferably 70℃. In step S3, 100g of cholanamide, 200ml of ethanol, and 25g of 1,3-dichloropropane are refluxed for 6 hours. In step S4, 200ml of water, 30g of sodium sulfite, and 1g of copper chloride are added, and the mixture is refluxed for 10 hours. In step S4, desalination is performed using an electrodialysis device. In step S4, drying is performed at 65-75°C, preferably 70°C. This method eliminates the need for sulfonation with propane sulpholactone, instead using an alternative route that requires only water and ethanol as solvents, thus avoiding the use of DMF. Example

[0024] like Figure 1 100g of cholic acid was dissolved in 250ml of methanol, and 1g of p-toluenesulfonic acid was added and refluxed for 2 hours. The mixture was cooled, crystallized, filtered, and dried at approximately 50°C. The methanol was concentrated and crystallized again to obtain methyl cholate, which was then filtered and dried at approximately 50°C to obtain approximately 100g, with a yield of 96%.

[0025] like Figure 2 100g of methyl cholate, 100ml of N,N-dimethyl-1,3-diaminopropane, and 1g of p-toluenesulfonic acid were heated to 120°C and reacted for 16 hours. Most of the remaining N,N-dimethyl-1,3-diaminopropane was evaporated until a thick precipitate was formed. Crystals were added to water, filtered, and dried at approximately 70°C to obtain 84g of cholanamide, with a yield of 74%.

[0026] like Figures 3-4Cholinedine 100g, ethanol 200ml, 1,3-dichloropropane 25g, refluxed for 6 hours, solvent and excess dichloroethane were distilled under reduced pressure until thickened. 200ml water, sodium sulfite 30g, and copper chloride 1g were added, refluxed for 10 hours, desalted by electrodialysis, evaporated to crystallize, filtered, and dried at approximately 70°C to obtain 96g of 3-[3-(cholineamidopropyl)dimethylamino]propanesulfonic acid inner salt, yield 77%. The electrodialysis apparatus can be Jiangsu Ritai Environmental Engineering Co., Ltd., model DSADIV, with Ti-coated IrRu electrodes, a final conductivity of less than 50μs / cm, and an ion exchange membrane.

[0027] This invention abandons the sulfonation reaction using propane sulpholactone and instead uses an alternative route, thus requiring only water and ethanol as solvents and avoiding the use of DMF. The reaction yields 3-[3-(cholanamidopropyl)dimethylamino]propanesulfonic acid inner salt in four steps, producing a product with high purity and high yield. Although embodiments of the present invention have been disclosed above, they are not limited to the applications listed in the specification and embodiments. They can be applied to various fields suitable for the present invention. Other modifications can be easily made by those skilled in the art. Therefore, without departing from the general concept defined by the claims and their equivalents, the present invention is not limited to the specific details and the illustrations shown and described herein.

Claims

1. A method for preparing an inner salt of 3-[3-(cholanamidopropyl)dimethylamino]propanesulfonic acid, characterized in that, The following steps are involved: S1, cholic acid and p-toluenesulfonic acid were refluxed in methanol solvent, cooled, crystallized, filtered, and then dried to obtain product one; S2, Product 1, N,N-dimethyl-1,3-diaminopropane and p-toluenesulfonic acid were heated and reacted for a certain time. After the reaction, the mixture was evaporated to a thick consistency, added to water to crystallize, filtered and dried to obtain cholanamide. S3, choline, and 1,3-dichloropropane were refluxed in ethanol and distilled under reduced pressure until viscous to obtain product three. S4. Water, sodium sulfite, and copper chloride were added to product three, and the mixture was refluxed for a certain period of time to perform desalting treatment. Subsequently, the product was evaporated and crystallized, filtered, and dried to obtain 3-[3-(cholamidopropyl)dimethylamino]propanesulfonic acid inner salt.

2. The method for preparing the inner salt of 3-[3-(cholanamidopropyl)dimethylamino]propanesulfonic acid according to claim 1, characterized in that: In step S1, after filtration, methanol is concentrated and crystallized to obtain solid one, solid one is dried to obtain product two, and product two is added to product one.

3. The method for preparing the inner salt of 3-[3-(cholanamidopropyl)dimethylamino]propanesulfonic acid according to claim 1, characterized in that: In step S1, 100g of cholic acid, 250ml of methanol, and 1g of p-toluenesulfonic acid are refluxed for 2 hours.

4. The method for preparing the inner salt of 3-[3-(cholanamidopropyl)dimethylamino]propanesulfonic acid according to claim 1, characterized in that: In step S1, drying is performed at 40-60℃.

5. The method for preparing the inner salt of 3-[3-(cholanamidopropyl)dimethylamino]propanesulfonic acid according to claim 1, characterized in that: In step S2, 100g of methyl cholate, 100ml of N,N-dimethyl-1,3-diaminopropane and 1g of p-toluenesulfonic acid are heated to 120 degrees and reacted for 16 hours.

6. The method for preparing the inner salt of 3-[3-(cholanamidopropyl)dimethylamino]propanesulfonic acid according to claim 1, characterized in that: In step S2, drying is performed at 60-80℃.

7. The method for preparing the inner salt of 3-[3-(cholanamidopropyl)dimethylamino]propanesulfonic acid according to claim 1, characterized in that: In step S3, 100g of cholineamide, 200ml of ethanol, and 25g of 1,3-dichloropropane are refluxed for 6 hours.

8. The method for preparing the inner salt of 3-[3-(cholanamidopropyl)dimethylamino]propanesulfonic acid according to claim 1, characterized in that: In step S4, 200 ml of water, 30 g of sodium sulfite and 1 g of copper chloride are added, and the mixture is refluxed for 10 hours.

9. The method for preparing the inner salt of 3-[3-(cholanamidopropyl)dimethylamino]propanesulfonic acid according to claim 1, characterized in that: In step S4, desalination is performed using an electrodialysis device.

10. The method for preparing the inner salt of 3-[3-(cholanamidopropyl)dimethylamino]propanesulfonic acid according to claim 1, characterized in that: In step S4, drying is performed at 65-75℃.

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