CN115043747B - Crystallization method of trisodium caronate and prepared trisodium caronate crystals - Google Patents
Crystallization method of trisodium caronate and prepared trisodium caronate crystals Download PDFInfo
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- CN115043747B CN115043747B CN202210971122.XA CN202210971122A CN115043747B CN 115043747 B CN115043747 B CN 115043747B CN 202210971122 A CN202210971122 A CN 202210971122A CN 115043747 B CN115043747 B CN 115043747B
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- SOBHUZYZLFQYFK-UHFFFAOYSA-K trisodium;hydroxy-[[phosphonatomethyl(phosphonomethyl)amino]methyl]phosphinate Chemical compound [Na+].[Na+].[Na+].OP(O)(=O)CN(CP(O)([O-])=O)CP([O-])([O-])=O SOBHUZYZLFQYFK-UHFFFAOYSA-K 0.000 title claims abstract description 105
- 238000002425 crystallisation Methods 0.000 title claims abstract description 51
- 239000013078 crystal Substances 0.000 title claims abstract description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 78
- 230000008025 crystallization Effects 0.000 claims abstract description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 34
- 239000007864 aqueous solution Substances 0.000 claims abstract description 30
- 238000002156 mixing Methods 0.000 claims abstract description 27
- 239000002904 solvent Substances 0.000 claims abstract description 27
- 238000000034 method Methods 0.000 claims abstract description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 22
- 239000002994 raw material Substances 0.000 claims abstract description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 36
- 239000012065 filter cake Substances 0.000 claims description 14
- 238000003756 stirring Methods 0.000 claims description 14
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 10
- 238000002386 leaching Methods 0.000 claims description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- 238000001035 drying Methods 0.000 claims description 8
- 230000002457 bidirectional effect Effects 0.000 claims description 5
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 claims description 2
- 229940011051 isopropyl acetate Drugs 0.000 claims description 2
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 230000001681 protective effect Effects 0.000 claims description 2
- 238000001291 vacuum drying Methods 0.000 claims description 2
- 230000001376 precipitating effect Effects 0.000 claims 1
- 239000000243 solution Substances 0.000 abstract description 8
- 239000002253 acid Substances 0.000 abstract description 4
- 238000005265 energy consumption Methods 0.000 abstract description 3
- 238000011031 large-scale manufacturing process Methods 0.000 abstract 1
- 239000007787 solid Substances 0.000 description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 239000008213 purified water Substances 0.000 description 7
- 238000000967 suction filtration Methods 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000001502 supplementing effect Effects 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 238000004108 freeze drying Methods 0.000 description 3
- 239000011259 mixed solution Substances 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- 230000001133 acceleration Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 229910052688 Gadolinium Inorganic materials 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002405 nuclear magnetic resonance imaging agent Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/38—Separation; Purification; Stabilisation; Use of additives
- C07C227/40—Separation; Purification
- C07C227/42—Crystallisation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C229/06—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton
- C07C229/10—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings
- C07C229/16—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of hydrocarbon radicals substituted by amino or carboxyl groups, e.g. ethylenediamine-tetra-acetic acid, iminodiacetic acids
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Crystallography & Structural Chemistry (AREA)
- Peptides Or Proteins (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a crystallization method of trisodium carproloate and prepared trisodium carproloate crystals. A method for the crystallization of trisodium caroate comprising the steps of: (1) Dissolving an oily trisodium caronate raw material in methanol, and then adding water; or dissolving the oily trisodium caronate raw material in water, and then adding methanol to prepare a trisodium caronate alcohol water solution; (2) Fully mixing a trisodium Carlo acid alcohol aqueous solution with a poor solvent to precipitate crystals; and (3) carrying out post-treatment to obtain the trisodium caroate crystals. The invention adopts a three-phase crystallization mode of alcohol, water and poor solvent, solves the problem of difficult crystallization of the trisodium carprofonate, has low equipment requirement, does not need high energy consumption, can be used for large-scale production, and has good product properties, high purity and high crystallization yield.
Description
Technical Field
The invention belongs to the technical field of crystallization methods, and further relates to a crystallization method of trisodium carprolate and trisodium carprolate crystals obtained by preparation.
Background
As the first liver-specific magnetic resonance imaging contrast agent 'Pumei' approved to be on the market in the United states, the variety belongs to gadolinium chelating agents, and the injection preparation of the variety contains important auxiliary material trisodium caronate, so that almost no related reports of the trisodium caronate exist at present. The trisodium carprolonate is characterized by easy moisture absorption and difficult crystallization, and a fixed-form product cannot be obtained by a common crystallization method, and the trisodium carprolonate product crystal can be obtained only after the trisodium carprolonate is treated by a freeze drying technology.
However, the preparation of the trisodium carproate crystal by the freeze-drying method has high requirements on equipment, high equipment cost and energy consumption thereof, and high mass production cost.
The existing prepared trisodium carprolonate is oily at room temperature, and the oily matter is generally wrapped with a solvent, so that the content of the prepared trisodium carprolonate is unstable during detection and is easy to deteriorate; especially, when the compound is used as a pharmaceutic adjuvant, the compound easily causes great influence on the quality of products. There is therefore a need to obtain a stable quality, accurate content of trisodium caronate product. The crystalline form of trisodium caronate product meets the above requirements very well.
Therefore, there is a need for a less costly and simpler crystallization process.
Disclosure of Invention
In order to solve the problems in the prior art, the invention provides a crystallization method of trisodium carproate and a prepared trisodium carproate crystal. The invention adopts a three-phase crystallization mode of alcohol, water and poor solvent, and the trisodium carprolate with good properties and high purity can be obtained by three dropping modes of trisodium carprolate alcohol aqueous solution and poor solvent, and the crystallization yield is high.
One of the objects of the present invention is to provide a method for crystallization of trisodium carproloate, comprising the steps of:
step 1: dissolving an oily trisodium caronate raw material in methanol, and then adding water; or dissolving the oily trisodium carproate raw material in water, and then adding methanol to prepare aqueous solution of trisodium carproate alcohol;
and 2, step: fully mixing a trisodium Carlo acid alcohol aqueous solution with a poor solvent to precipitate crystals;
and step 3: post-treatment to obtain the trisodium carprolonate crystal.
In the step (1) of the present invention, methanol or water is added first, and the crystallization effect is not greatly affected.
In the crystallization process of trisodium carproloate according to the invention, preferably:
in the step 1, in a solution of the trisodium caronate in water, the volume ratio of methanol to water is 1:0.01 to 10, for example, may be 1:0.01, 1:0.1, 1:0.5, 1:1. 1:1.5, 1:2. 1:2.5, 1:3. 1:3.5, 1: 4. 1: 5. 1: 6. 1: 7. 1: 8. 1: 9. 1:10 and any range between any two values;
the mass ratio of the trisodium caronate raw material to the methanol is 1:0.8 to 1:8, for example, may be 1:0.8, 1:0.9, 1:1. 1:1.2, 1:1.5, 1:2. 1:2.5, 1:3. 1:3.5, 1: 4. 1: 5. 1: 6. 1: 7. 1:8, and any range between any two values.
In the crystallization process of trisodium caronate according to the invention, preferably:
in step 2, the poor solvent is at least one selected from methyl tert-butyl ether, isopropyl acetate, acetone, toluene, isopropanol, dichloromethane and ethanol.
In the crystallization process of trisodium carproloate according to the invention, preferably:
in step 2, the volume ratio of the aqueous solution of the trisodium carprolate to the poor solvent is 1:5 to 1:25, for example, may be 1: 5. 1: 7. 1: 9. 1: 11. 1: 13. 1: 15. 1: 18. 1: 20. 1: 22. 1:25, and any range there between.
In the crystallization process of trisodium carproloate according to the invention, preferably:
in the step 2, the aqueous solution of trisodium caronate and the poor solvent are fully mixed by firstly dropwise adding and mixing, and then stirring for further mixing.
In the crystallization process of trisodium carproloate according to the invention, preferably:
in the step 2, the dropping and mixing mode is at least one of dropping a trisodium caronate alcohol aqueous solution into a poor solvent for mixing, dropping the poor solvent into the trisodium caronate alcohol aqueous solution for mixing, and dropping the trisodium caronate alcohol aqueous solution and the poor solvent in a bidirectional manner for mixing;
the dropping and mixing time is 1 to 3h, for example, 1, 1.5, 2, 2.5, 3h and any range formed by any two numerical values;
preferably, when the aqueous solution of trisodium caronate alcohol and the poor solvent are mixed in a bidirectional dropwise manner, the ratio of the dropping speed of the aqueous solution of trisodium caronate alcohol to the dropping speed of the poor solvent is 1:1-12, for example, may be 1:1. 1:2. 1:3. 1: 4. 1: 5. 1: 6. 1: 7. 1: 8. 1: 9. 1: 10. 1: 11. 1:12 and any range between any two values.
In the crystallization process of trisodium carproloate according to the invention, preferably:
in the step 2, stirring for 30min to 3h; for example, the time period can be 30min, 1, 1.5, 2, 2.5, 3h and any range between any two values;
the stirring temperature is 20 to 40 ℃, and can be, for example, 20, 25, 30, 35, 40 ℃ or any range between any two values.
In the crystallization process of trisodium carproloate according to the invention, preferably:
in the step 3, the post-treatment mode comprises leaching under protective gas, leaching a filter cake by using a poor solvent, and then drying in vacuum to obtain the trisodium caronate crystal.
In the crystallization process of trisodium carproloate according to the invention, preferably:
the temperature of the vacuum drying is 45 to 55 ℃, and can be, for example, 45, 46, 47, 50, 52, 54, 55 ℃ and any range formed by any two values.
Another object of the present invention is to provide trisodium caronate crystals prepared by the crystallization method described in the first object of the present invention, wherein the purity of the trisodium caronate crystals is 90 to 99%, for example, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 ℃, and any range of composition between any two values.
The trisodium carprolonate is easy to absorb moisture, difficult to crystallize and easy to dissolve in water, and the trisodium carprolonate crystal cannot be obtained by the traditional crystallization method.
The trisodium caronate of the invention has the structural formula:
the method comprises the steps of adding methanol into an oily substance of a trisodium carproate product, supplementing a certain amount of purified water into a methanol solution of the trisodium carproate to prepare a mixed solution, mixing the mixed solution with a poor solvent at a certain speed, mixing the mixed solution in three dropping modes (positive dropping, reverse dropping and bidirectional dropping), and performing suction filtration to obtain a white-like crystal after mixing for a certain time.
The endpoints of the ranges and any values disclosed in the present application are not limited to the precise range or value, and such ranges or values should be understood to encompass values close to those ranges or values. For ranges of values, between the endpoints of each of the ranges and the individual points, and between the individual points may be combined with each other to give one or more new ranges of values, and these ranges of values should be considered as specifically disclosed herein. In the following, various technical solutions can in principle be combined with each other to obtain new technical solutions, which should also be regarded as specifically disclosed herein.
Compared with the prior art, the invention has at least the following advantages:
the invention solves the problem of difficult crystallization of the trisodium carprolonate, has low equipment requirement and no need of high energy consumption, can be used for scale-up production, and can obtain products with good properties, high purity and high crystallization yield.
Drawings
FIG. 1 is a schematic flow diagram of a prior art trisodium caronate crystallization process;
FIG. 2 is a schematic flow chart of the trisodium caronate crystallization process of example 1 according to the invention;
FIG. 3 is a schematic flow chart of the trisodium caronate crystallization process of example 2 according to the invention;
figure 4 is a schematic flow diagram of the trisodium carprolonate crystallization process of example 3 of the present invention.
Detailed Description
While the present invention will be described in detail and with reference to the specific embodiments thereof, it should be understood that the following detailed description is merely illustrative of the present invention and should not be taken as limiting the scope of the present invention, but is intended to cover modifications and variations thereof that would occur to those skilled in the art upon reading the present disclosure.
It is to be further understood that the various features described in the following detailed description may be combined in any suitable manner without departing from the scope of the invention. The invention is not described in detail in order to avoid unnecessary repetition.
In addition, any combination of the various embodiments of the present invention can be made, as long as the technical solution formed by the combination does not depart from the idea of the present invention, and the technical solution formed by the combination is part of the original disclosure of the present specification, and also falls into the protection scope of the present invention.
The raw materials used in the examples and comparative examples are disclosed in the prior art if not particularly limited, and may be, for example, directly purchased or prepared according to the preparation methods disclosed in the prior art.
CAS:207230-20-4 of the starting material for trisodium carolinate was purchased from Yuntang Luzhong pharmaceuticals, inc.
Example 1
Adding 100 mL (about 79 g) of methanol into 50g pure trisodium caronate oily substance, detecting water content, adding 7.5 mL of purified water, uniformly mixing, dropwise adding trisodium caronate methanol aqueous solution (normal drop) into 1000 mL of ethyl acetate, wherein the dropwise adding time is 1h as shown in figure 2, stirring for 1h at 25 ℃ after the dropwise adding is finished, carrying out suction filtration under the protection of nitrogen, leaching a filter cake with 50 mL of ethyl acetate, and drying the filter cake in a 55 ℃ reduced pressure oven until the water content is less than or equal to 3.0% to obtain 46.2g of white-like solid (the crystallization yield is 92.4%) and the purity is 99.7%.
Example 2
Adding 100 mL of methanol into trisodium carproate (containing 50g of pure product) oily matter, then adding 7.5 mL of purified water, uniformly mixing, dropwise adding 1000 mL of ethyl acetate into trisodium carproate methanol aqueous solution (anti-dropping), as shown in figure 3, dropwise adding for 1h, stirring for 1h at 25 ℃ after dropwise adding, carrying out suction filtration under the protection of nitrogen, leaching a filter cake with 50 mL of ethyl acetate, and drying the filter cake in a reduced-pressure oven at 55 ℃ until the water content is less than or equal to 3.0%, thus obtaining 44.6g of white-like solid (the crystallization yield is 89.2%) with the purity of 99.6%.
Example 3
Adding 100 mL of methanol into oily substance of trisodium caronate (containing 50g of pure product), then adding 7.5 mL of purified water, uniformly mixing, simultaneously dropwise adding 1000 mL of ethyl acetate and aqueous solution of trisodium caronate methanol into a 2L four-mouth bottle, wherein the dropwise adding speed of ethyl acetate is 15.03g/min, the acceleration of the droplet of aqueous solution of trisodium caronate methanol is 2.28g/min, stirring and starting (bidirectionally dropwise adding) the four-mouth bottle, stirring for 1h at 25 ℃ after the dropwise adding is finished, performing suction filtration under the protection of nitrogen, leaching a filter cake by using 50 mL of ethyl acetate, drying the filter cake in a vacuum oven at 55 ℃ until the water content is less than or equal to 3.0%, and obtaining 45.8g of white-like solid (the crystallization yield is 91.6%) with the purity of 99.8%.
As can be seen from examples 1-3, the trisodium caronate with good properties and high purity can be obtained by three dropping modes of the aqueous solution of trisodium caronate and the poor solvent, and the crystallization yield is high.
Example 4
Adding 100 mL of anhydrous methanol into 50g of pure trisodium Carolinate oily substance, detecting water content, supplementing 8 mL of purified water, uniformly mixing, simultaneously dropwise adding 1200 mL of acetone and aqueous solution of trisodium Carolinate methanol into a 2L four-port bottle, wherein the dropwise adding speed of ethyl acetate is 16g/min, the acceleration of the drop of aqueous solution of trisodium Carolinate methanol is 4g/min, stirring and starting the four-port bottle at the beginning of dropwise adding, stirring for 3h at 20 ℃ after dropwise adding, carrying out suction filtration under the protection of nitrogen, leaching a filter cake by using 60 mL of ethyl acetate, drying the filter cake in a 45 ℃ reduced pressure oven until the water content is less than or equal to 3.0%, and obtaining 45.6g of white-like solid (the crystallization yield is 91.2%) with the purity of 99.4%.
Example 5
Adding 100 mL of methanol into 50g of pure trisodium Carlo acid oily substance, detecting water content, supplementing 6mL of purified water, uniformly mixing, dropwise adding aqueous solution (normal drop) of trisodium Carlo acid methanol into 900 mL of acetone for 1h, stirring for 1h at 40 ℃ after dropwise adding, carrying out suction filtration under the protection of nitrogen, leaching a filter cake with 50 mL of ethyl acetate, drying the filter cake in a 55 ℃ reduced pressure oven until the water content is less than or equal to 3.0%, and obtaining 46.2g of white-like solid (the crystallization yield is 92.4%) with the purity of 99.4%.
Example 6
Adding 100 mL of methanol into trisodium carproate (containing 50g of pure product) oily matter, detecting water content, supplementing 7mL of purified water, uniformly mixing, dropwise adding trisodium carproate methanol aqueous solution (normal drop) into 950 mL of toluene for 1h, stirring at 35 ℃ for 2h after dropwise adding, carrying out suction filtration under the protection of nitrogen, leaching a filter cake with 50 mL of ethyl acetate, drying the filter cake in a 50 ℃ reduced pressure oven until the water content is less than or equal to 3.0%, and obtaining 46.8g of white-like solid (the crystallization yield is 93.5%) with the purity of 99.5%.
Example 7
It was substantially the same as in example 1 except that the amount of water added was 2ml, and an off-white solid was obtained in an amount of 46.0g (crystallization yield 92.0%) and a purity of 92.7%.
Example 8
It was substantially the same as in example 1 except that the amount of water added was 20ml, and an off-white solid was obtained in an amount of 35.8g (crystallization yield: 71.6%) and a purity of 99.3%.
Comparative example 1
And adding 100 mL of methanol into the oily substance of the trisodium caronate (containing 50g of pure product), heating to reflux for 30min, slowly cooling to room temperature until no solid is separated out, and continuously cooling to-10 to 0 ℃ until no solid is separated out.
It can be seen from a comparison of the results of the inventive example with the results of comparative example 1 that the addition of water has a significant influence on the crystallization process of trisodium carolinate.
Comparative example 2
Adding 100 mL of water into trisodium caronate (containing 50g of pure product) oily matter, mixing, slowly cooling to room temperature until no solid is precipitated, continuously cooling to 0-5 ℃, still no solid is precipitated, and directly freeze-drying the aqueous solution to obtain 49.5g of white solid (crystallization yield is 99.0%) with purity of 99.5%. The specific process flow is shown in figure 1.
The invention has been described in detail with reference to specific embodiments and illustrative examples, but the description is not intended to limit the invention. Those skilled in the art will appreciate that various equivalent substitutions, modifications or improvements may be made to the technical solution of the present invention and its embodiments without departing from the spirit and scope of the present invention, which fall within the scope of the present invention. The scope of the invention is defined by the appended claims.
Claims (7)
1. A method for crystallization of trisodium carprolate, comprising the steps of:
step 1: dissolving an oily trisodium caronate raw material in methanol, and then adding water; or dissolving the oily trisodium carproate raw material in water, and then adding methanol to prepare aqueous solution of trisodium carproate alcohol;
step 2: fully mixing a trisodium caronate alcohol aqueous solution and a poor solvent, and precipitating crystals;
and step 3: post-treating to obtain trisodium caronate crystals;
in step 2, the poor solvent is at least one selected from isopropyl acetate, acetone, toluene and ethyl acetate.
2. Process for the crystallization of trisodium carprolac according to claim 1, characterized in that:
in step 2, the volume ratio of the aqueous solution of the trisodium carprolate to the poor solvent is 1:5 to 1:25.
3. process for the crystallization of trisodium caronate according to claim 1, characterized in that:
in step 2, the fully mixing mode of the aqueous solution of the trisodium carprolate and the poor solvent is to firstly drop-drop mix and then stir for further mixing.
4. Process for the crystallization of trisodium carprolac according to claim 3, characterized in that:
in the step 2, the dropping and mixing mode is at least one of dropping a trisodium caronate alcohol aqueous solution into a poor solvent for mixing, dropping the poor solvent into the trisodium caronate alcohol aqueous solution for mixing, and dropping the trisodium caronate alcohol aqueous solution and the poor solvent in a bidirectional manner for mixing;
the dropping and mixing time is 1 to 3h.
5. Process for the crystallization of trisodium carprolac according to claim 3, characterized in that:
in the step 2, stirring for 30min to 3h;
the stirring temperature is 20 to 40 ℃;
when the aqueous solution of the trisodium caronate alcohol and the poor solvent are mixed in a bidirectional dropping manner, the dropping speed ratio of the aqueous solution of the trisodium caronate alcohol to the poor solvent is 1:1-12.
6. Process for the crystallization of trisodium carprolac according to claim 1, characterized in that:
in the step 3, the post-treatment mode comprises leaching under protective gas, leaching a filter cake by using a poor solvent, and then drying in vacuum to obtain the trisodium caronate crystal.
7. Process for the crystallization of trisodium caronate according to claim 6, characterized in that:
the temperature of the vacuum drying is 45 to 55 ℃.
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