CN114031496A - Preparation method of high-purity pravastatin 1,1,3, 3-tetramethylbutylamine - Google Patents
Preparation method of high-purity pravastatin 1,1,3, 3-tetramethylbutylamine Download PDFInfo
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- C07C67/00—Preparation of carboxylic acid esters
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/68—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton
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Abstract
The invention belongs to the technical field of pharmacy, and particularly relates to a preparation method of high-purity pravastatin 1,1,3, 3-tetramethylbutylamine; dissolving pravastatin sodium at the temperature lower than 10 ℃, extracting the pravastatin sodium at low temperature by butyl acetate, reacting the pravastatin sodium with 1,1,3, 3-tetramethylbutylamine, concentrating and separating the solution under reduced pressure to break the balance of a system to separate out the pravastatin 1,1,3, 3-tetramethylbutylamine, and further reacting the pravastatin sodium with the 1,1,3, 3-tetramethylbutylamine in an acetone solution to obtain the high-purity pravastatin 1,1,3, 3-tetramethylbutylamine; the preparation method of the invention greatly reduces the content of isomer impurities and lactonization impurities, has stable preparation method and good repeatability, and the purity of the obtained pravastatin 1,1,3, 3-tetramethylbutylamine can reach 99.791 percent and can be used as a quality control method of pravastatin 1,1,3, 3-tetramethylbutylamine.
Description
Technical Field
The invention belongs to the technical field of pharmacy, and particularly relates to a preparation method of high-purity pravastatin 1,1,3, 3-tetramethylbutylamine.
Technical Field
Pravastatin Sodium Pravastatin Sodium is an inhibitor of 3-hydroxy 3-methylglutaryl coenzyme A reductase (HMG-COA reductase) and has the following structural formula:
the pravastatin sodium can effectively reduce serum total cholesterol, low-density lipoprotein and triglyceride and increase high-density lipoprotein by inhibiting the synthesis of cholesterol in a human body, is initially used for treating hyperlipidemia and familial hypercholesterolemia, has continuously expanded indications afterwards, can slow down the development of atherosclerosis, and reduces the occurrence of coronary atherosclerotic lesions and clinical cardiovascular events; after the pravastatin is taken for a long time, the death rate caused by various reasons can be reduced no matter whether a patient has coronary heart disease or not, and the pravastatin becomes the only medicine which can be used for the first-level and second-level defense of the heart disease and the apoplexy of the patient with high cholesterol level or coronary heart disease at present. Therefore, the quality of pravastatin sodium directly affects the efficacy of the drugs, and further extends to the cost and popularity of the drugs. In the process of preparing related medicaments, pravastatin 1,1,3, 3-tetramethylbutylamine is commonly used as a standard substance to detect the content of a finished product of a pravastatin sodium raw material medicament or the content of related substances, and the structural formula is as follows:
because pravastatin 1,1,3, 3-tetramethylbutylamine has the advantages of no moisture absorption, stability, suitability for use and the like, the pravastatin 1,1,3, 3-tetramethylbutylamine is an excellent substance as a reference substance. At present, pravastatin 1,1,3, 3-tetramethylbutylamine is usually purchased from pharmacopoeia committee or professional institutions as a first-class standard substance, and is high in price, and the cost is high if the pravastatin 1,1,3, 3-tetramethylbutylamine is used for daily detection; on the other hand, pravastatin sodium has hygroscopicity, and if the purity of pravastatin sodium is not high, the accuracy of a detection result is seriously influenced by further moisture absorption. However, no technology is disclosed at present how to stably and efficiently prepare high-purity pravastatin 1,1,3, 3-tetramethylbutylamine, so how to obtain high-purity and high-stability pravastatin 1,1,3, 3-tetramethylbutylamine is of great significance for preparation and detection of statins.
Disclosure of Invention
Aiming at the problems in the prior art, the invention aims to provide a preparation method of high-purity pravastatin 1,1,3, 3-tetramethylbutylamine.
The specific technical scheme of the invention is as follows:
s1, weighing pravastatin sodium, adding purified water precooled to below 10 ℃, and stirring;
s2, adding butyl acetate into S1, adding an acetic acid solution under the stirring condition to adjust the pH value, wherein the time from the beginning of adding the acetic acid solution to the end of extraction is 15min, and the temperature of the solution is kept below 10 ℃ in the extraction process;
s3, standing and layering after extraction to obtain a butyl acetate layer;
s4, adding 0.01-0.03 time of 1,1,3, 3-tetramethylbutylamine into the butyl acetate layer, and stirring for 5-6 min;
s5, concentrating the solution obtained in the step S4 under reduced pressure until the solution becomes turbid and more precipitates are observed to be generated, then placing the solution in ice water for cooling and filtering, and soaking a filter cake with butyl acetate, washing and filtering;
s6, continuing carrying out vacuum filtration on the S5 filter cake until the filter cake is dry, adding fresh acetone, 1,3, 3-tetramethylbutylamine and purified water, heating to 30-35 ℃, continuously stirring for 2 hours, cooling in ice water, filtering slurry, and discarding mother liquor to obtain pravastatin 1,1,3, 3-tetramethylbutylamine wet powder;
s7, drying the pravastatin 1,1,3, 3-tetramethylbutylamine wet powder obtained in the S6 for 7-8 hours under the vacuum condition of 30-40 ℃ to obtain the high-purity pravastatin 1,1,3, 3-tetramethylbutylamine.
Further, the volume of the purified water added in the step S1 is 5-10 times of the mass of the pravastatin sodium;
further, the addition amount of the butyl acetate in the step S2 is 1-5 times of the volume of the solution in the step S1;
further, the butyl acetate in the step S2 is pre-cooled to below 10 ℃;
further, the mass concentration of the acetic acid solution added in the step S2 is 20-30%;
further, the pH adjustment target value is 3.5-4.5;
further, the temperature of the concentration under reduced pressure in the step S5 is not higher than 35 ℃;
further, the butyl acetate soaking time in the step S5 is 10-30 min;
further, the volume of the fresh acetone added in the step S6 is 4-8 times (v/w) of the weight of the dry solid after suction filtration;
further, in the step S6, the volume ratio of the fresh acetone, the 1,1,3, 3-tetramethylbutylamine and the purified water is 4-8: 0.2: 0.1.
In the technical scheme of the experiment, pravastatin sodium is dissolved at the temperature lower than 10 ℃, butyl acetate is adopted for extraction at the low temperature, the main purpose is to reduce isomer impurities and lactonization impurities generated after the pravastatin sodium is acidified and converted into pravastatin acid at the low temperature, then the generated pravastatin acid reacts with 1,1,3, 3-tetramethylbutylamine, and the balance of a mixed solution system is broken through concentration, so that pravastatin 1,1,3, 3-tetramethylbutylamine which is originally insoluble in butyl acetate is naturally separated out from the mixed system. And the solid is washed by butyl acetate again to remove residual impurities, so that the obtained purity is good. Adding 1,1,3, 3-tetramethylbutylamine into an acetone aqueous solution to make a solution system alkaline, and further reacting lactone possibly generated during acidification again to obtain high-purity pravastatin 1,1,3, 3-tetramethylbutylamine; the preparation method strictly controls the temperature condition in the process, and avoids the decomposition of raw materials and products and the introduction of impurities.
Compared with the prior art, the invention has the following beneficial effects:
the preparation method of the high-purity pravastatin 1,1,3, 3-tetramethylbutylamine provided by the invention has the advantages of simple preparation process, stable preparation method and good repeatability, the purity of the obtained pravastatin 1,1,3, 3-tetramethylbutylamine is up to 99.791%, and the pravastatin 1,1,3, 3-tetramethylbutylamine can be used as a standard substance for detecting the sodium content of pravastatin and related substances and can be used for detection.
(1) According to the invention, the pravastatin sodium is dissolved at the temperature lower than 10 ℃, and butyl acetate is used for extraction at low temperature, so that the content of isomer impurities and lactonization impurities generated after the pravastatin sodium is acidified and converted into pravastatin acid is reduced, and the purity of the product is improved;
(2) the invention adopts the reaction of pravastatin acid and 1,1,3, 3-tetramethylbutylamine, destroys the balance of a mixed solution system through decompression and concentration, leads the pravastatin 1,1,3, 3-tetramethylbutylamine to be naturally separated out from a butyl acetate mixed system, and has better purity and simple process method;
(3) the invention adopts twice reactions with 1,1,3, 3-tetramethylbutylamine, and the second reaction is carried out in alkaline acetone water solution, and lactone possibly generated during acidification can be further reacted again to obtain high-purity pravastatin 1,1,3, 3-tetramethylbutylamine;
(4) the preparation method strictly controls the temperature conditions in the process, avoids the decomposition of raw materials and products and the introduction of impurities, obtains the pravastatin 1,1,3, 3-tetramethylbutylamine with the purity of 99.791 percent, has high safety, simple process flow and easy operation, and is convenient for industrial scale popularization and application.
Drawings
FIG. 1 is a high performance liquid chromatogram of high purity pravastatin 1,1,3, 3-tetramethylbutylamine prepared in example 1.
Detailed Description
Experimental procedures according to the invention, in which no particular conditions are specified in the following examples, are generally carried out under conventional conditions, or under conditions recommended by the manufacturer. The various chemicals used in the examples are commercially available.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.
The terms "comprising" and "having," and any variations thereof, are intended to cover non-exclusive inclusions. For example, a process, method, apparatus, article, or device that comprises a list of steps is not limited to only those steps or modules listed, but may alternatively include other steps not listed or inherent to such process, method, article, or device.
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the description is intended to be exemplary only, and is not intended to limit the scope of the present invention. Moreover, in the following description, descriptions of well-known structures and techniques are omitted so as to not unnecessarily obscure the concepts of the present invention.
All other embodiments obtained by a person skilled in the art without making any inventive step based on the embodiments of the present invention are within the scope of the present invention, and the following embodiments further describe the present invention, but the present invention is not limited to the embodiments.
The method for determining the purity of pravastatin 1,1,3, 3-tetramethylbutylamine prepared in the specific embodiment of the invention is as follows:
the method for measuring the content of the pravastatin 1,1,3, 3-tetramethylbutylamine and related substances adopts a method for measuring pravastatin sodium in United states pharmacopoeia or Chinese pharmacopoeia, the detection wavelength is 238nm, a chromatographic column is a C18 column with the thickness of 10cm multiplied by 4.0mm multiplied by 3.0 mu m, the column temperature is 25 ℃, the sample box temperature is 15 ℃, the flow rate is 1.0mL/min, and gradient elution is adopted, which is detailed in the United states pharmacopoeia or Chinese pharmacopoeia.
Example 1
S1, accurately weighing 50g of pravastatin sodium, adding 500mL of purified water precooled to 10 ℃, and stirring until the pravastatin sodium is completely dissolved;
s2, adding 2 times volume of butyl acetate which is pre-cooled to 10 ℃ into S1, adding an acetic acid solution with the mass concentration of 30% under the stirring condition to adjust the pH value to 3.5, controlling the time from the beginning of adding the acetic acid solution to the end of extraction to be 15min, and keeping the solution at 10 ℃ in the extraction process;
s3, standing for 5min after extraction is finished, separating a water layer and a butyl acetate layer, adding a small amount of water layer into an undistributed middle layer for continuous extraction, and combining butyl acetate layers to mark as extract 1;
s4, immediately adding 30mL of 1,1,3, 3-tetramethylbutylamine into the extract 1, and stirring for 6 min;
s5, concentrating the solution obtained in the step S4 under the conditions of vacuumizing and 33 ℃ until the solution becomes turbid and more precipitates are observed, then placing the solution in ice water for cooling and filtering, soaking a filter cake in 50mL of butyl acetate for 20min, washing and filtering, and discarding a mother solution;
s6, continuously pumping the S5 filter cake for 10 minutes, adding fresh acetone with the weight 5 times (v/w) that of the filter cake, then adding 1,1,3, 3-tetramethylbutylamine with the weight 0.2 times (v/w) that of the filter cake and purified water with the weight 0.1 times (v/w) that of the filter cake, heating to 35 ℃, continuously stirring for about 2 hours, placing the mixture in ice water for cooling, filtering slurry, and discarding mother liquor to obtain pravastatin 1,1,3, 3-tetramethylbutylamine wet powder;
s7, drying the pravastatin 1,1,3, 3-tetramethylbutylamine wet powder obtained in the S6 for 7.5 hours under the vacuum condition of 40 ℃ to obtain 40.26g of pravastatin 1,1,3, 3-tetramethylbutylamine with the purity of 99.741 percent;
s8, subpackaging the high-purity pravastatin 1,1,3, 3-tetramethylbutylamine product by using a PE bag or a sample bottle.
Example 2
The difference from the example 1 is that the purified water is precooled to 5 ℃ in the step S1, and the rest steps are the same as the example 1;
this example gives 40.42g of pravastatin 1,1,3, 3-tetramethylbutylamine with a purity of 99.750%.
Example 3
The difference from example 1 is that the acetic acid solution is adjusted to pH 4.0 in step S2, and the rest of the procedure is the same as example 1;
this example gives 40.35g of pravastatin 1,1,3, 3-tetramethylbutylamine with a purity of 99.768%.
Example 4
The difference from example 1 is that the acetic acid solution is adjusted to pH 4.5 in step S2, and the rest of the procedure is the same as example 1;
this example yielded 40.36g of pravastatin 1,1,3, 3-tetramethylbutylamine with a purity of 99.762%.
Example 5
The difference from example 1 is that the amount of 1,1,3, 3-tetramethylbutylamine added and the stirring time in step S4 are different, as shown in Table 1, and the rest of the steps are the same as example 1;
table 1: influence of the addition amount of 1,1,3, 3-tetramethylbutylamine and the stirring time on the product
| Numbering | 1,1,3, 3-tetramethylbutylamine | Time of stirring | Weight and purity of the product |
| 1 | 15mL | 3min | 35.45g，97.270％ |
| 2 | 20mL | 5min | 39.22g，99.522％ |
| 3 | 30mL | 5min | 40.30g，99.791％ |
| 4 | 35mL | 5min | 39.07g，98.234％ |
| 5 | 40mL | 3min | 38.85g，98.044％ |
The results of example 1 and table 1 show that, in step S4 of the present invention, the purity of the obtained product can reach 99.791% when the amount of 1,1,3, 3-tetramethylbutylamine added is 30mL and the stirring time is 5min, and the purity measurement result of number 3 is shown in fig. 1, while the excessive 1,1,3, 3-tetramethylbutylamine and the shortened stirring time all cause insufficient reaction, yield decrease and purity decrease.
Example 6
The difference from example 5 No. 3 is that the concentration temperature in S5 is different, see Table 2 specifically, and the rest steps are the same as example 5 No. 3;
table 2: effect of concentration temperature on product
| Numbering | Temperature of concentration | Weight and purity of the product |
| 6 | 25℃ | 40.21g，98.794％ |
| 7 | 30℃ | 40.25g，99.790％ |
| 8 | 35℃ | 40.28g，99.788％ |
| 9 | 38℃ | 39.82g，98.552％ |
| 10 | 40℃ | 39.05g，97.996％ |
From the results of table 2, it can be seen that the optimum concentration temperature of the solution in step S5 is 30-35 ℃, the purity of the obtained product can reach 99.788-99.791%, concentration below the temperature range can prolong the concentration time, increase impurities and reduce the purity, and the temperature exceeding the temperature range can cause the product to decompose, generate impurities and reduce the purity.
Example 7
The difference from example 5, No. 3, is that the amount of acetone and 1,1,3, 3-tetramethylbutylamine added in step S6 is different, as shown in table 3, and the rest steps are the same as example 5, No. 3;
table 3: effect of concentration temperature on product
| Numbering | Acetone (II) | 1,1,3, 3-tetramethylbutylamine | Weight and purity of the product |
| 11 | 2 times volume | 0.3 times volume | 37.88g，97.321％ |
| 12 | 3 times volume | 0.2 times volume | 39.84g，99.362％ |
| 13 | 5 times volume | 0.1 times volume | 40.05g，97.746％ |
| 14 | 4 times volume | 0.3 times volume | 37.24g，97.801％ |
| 15 | 8 times volume | 0.2 times volume | 40.25g，99.742％ |
Combining the results of example 5, No. 3 and table 3, it can be seen that the addition amounts of acetone and 1,1,3, 3-tetramethylbutylamine in step S6 have certain influence on the yield and purity of the product, when the volume of acetone is small and the volume of 1,1,3, 3-tetramethylbutylamine is large, a large amount of 1,1,3, 3-tetramethylbutylamine will remain in the product and the purity will be reduced, while a relatively large amount of 1,1,3, 3-tetramethylbutylamine will increase the solubility of the product and decrease the yield in the system.
Example 8
The difference from example 5 No. 3 is that the temperature and the stirring time in step S6 are different, as shown in Table 4, and the rest steps are the same as example 5 No. 3;
table 4: effect of temperature and stirring time on the product
| Numbering | Temperature of | Time of stirring | Weight and purity of the product |
| 16 | 25℃ | 3h | 37.50g，99.631％ |
| 17 | 30℃ | 2h | 40.06g，99.785％ |
| 18 | 35℃ | 3h | 39.98g，99.714％ |
| 19 | 40℃ | 1.5h | 39.81g，98.566％ |
| 20 | 40℃ | 2h | 39.73g，98.528％ |
Combining the results of example 5, No. 3 and Table 4, it can be seen that the temperature and stirring time in step S6 have some influence on the yield and purity of the product, wherein the optimal conditions are 35 ℃ and 2h, and below the temperature, the increase of stirring time may result in incomplete conversion of lactone impurities in the product, and the long-term stirring may increase the solubility of the product in the system, resulting in decreased yield and purity. Above this temperature, impurities are destroyed under constant stirring, resulting in a decrease in both yield and purity.
Example 9
The difference from example 5 No. 3 is that the drying conditions of the wet powder of pravastatin 1,1,3, 3-tetramethylbutylamine in step S7 are different, as shown in Table 5, and the rest steps are the same as example 5 No. 3;
table 5: effect of Pravastatin 1,1,3, 3-tetramethylbutylamine Wet powder drying conditions on the product
| Numbering | Drying temperature | Drying time | Purity of the product |
| 21 | 30℃ | 8h | 99.790％ |
| 22 | 40℃ | 8h | 99.782％ |
| 23 | 50℃ | 7h | 98.786％ |
| 24 | 60℃ | 6h | 98.742％ |
| 25 | 70℃ | 5h | 97.518％ |
Combining the results of example 5, No. 3 and Table 5, it can be seen that the drying conditions of the wet powder of pravastatin 1,1,3, 3-tetramethylbutylamine in step S7 have some influence on the purity of the product, wherein the drying temperature is 40 ℃, the drying time is 7.5h, the drying temperature is 30 ℃ and the drying time is 8h are preferred, and the reduction of the drying time due to the increase of the drying temperature or the reduction of the drying temperature may lead to the introduction of impurities or the decomposition of the product, thereby reducing the purity of the product.
Comparative example 1
The difference from the example 1 is that the purified water in S1 is precooled to 12 ℃, and the rest steps are the same as the example 1;
this example yielded 39.40g of pravastatin 1,1,3, 3-tetramethylbutylamine with a purity of 98.694%;
further combining the data of example 1, it is shown that the precooling temperature of purified water in S1 is higher than 10 ℃, and the yield and purity of pravastatin 1,1,3, 3-tetramethylbutylamine are reduced, probably because the solution is acidified and extracted under relatively high temperature conditions, thereby producing isomer and lactone impurities, which are not effectively removed and converted in the subsequent process, thereby reducing the yield and purity of the product.
Comparative example 2
The difference from the example 1 is that the purified water in S1 is precooled to 15 ℃, and the rest steps are the same as the example 1;
this example yielded 38.96g of pravastatin 1,1,3, 3-tetramethylbutylamine with a purity of 97.355%;
further combining the data of example 1, it is shown that the precooling temperature of purified water in S1 is higher than 10 ℃, and the yield and purity of pravastatin 1,1,3, 3-tetramethylbutylamine are reduced, probably because the solution is acidified and extracted under relatively high temperature conditions, thereby producing isomer and lactone impurities, which are not effectively removed and converted in the subsequent process, thereby reducing the yield and purity of the product.
Comparative example 3
The difference from example 1 is that pH in S2 is 3.0, and the rest of the procedure is the same as example 1;
this example yielded 38.16g of pravastatin 1,1,3, 3-tetramethylbutylamine with a purity of 98.062%;
further combining the data of examples 1,3 and 4, it is shown that the optimum range of pH in S2 is 3.5-4.5, below which the yield and purity of pravastatin 1,1,3, 3-tetramethylbutylamine are decreased, possibly because the increased acidity results in a solution with more isomer and lactone impurities at relatively low pH, and the impurities are not effectively removed and converted in the subsequent processes, resulting in decreased product yield and purity.
Comparative example 4
The difference from example 1 is that pH in S2 is 5.0, and the rest of the procedure is the same as example 1;
this example yielded 30.42g of pravastatin 1,1,3, 3-tetramethylbutylamine with a purity of 99.755%;
further combining the data of examples 1,3 and 4, it was shown that the optimum range of pH in S2 was 3.5 to 4.5, above which the yield of pravastatin 1,1,3, 3-tetramethylbutylamine decreased, probably because the decreased acidity resulted in a failure of better conversion of pravastatin sodium to pravastatin acid reacting with 1,1,3, 3-tetramethylbutylamine, resulting in a decrease in yield.
The test results show that the preparation method of pravastatin 1,1,3, 3-tetramethylbutylamine has the advantages of good stability and good repeatability, and the prepared pravastatin 1,1,3, 3-tetramethylbutylamine has high yield and purity and can be used as a quality control method of pravastatin 1,1,3, 3-tetramethylbutylamine.
It should be understood that the above examples are only for clarity of illustration and are not intended to limit the embodiments. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. And obvious variations or modifications therefrom are within the scope of the invention.
Claims (10)
1. A preparation method of high-purity pravastatin 1,1,3, 3-tetramethylbutylamine is characterized by comprising the following steps:
s1, weighing pravastatin sodium, adding purified water precooled to below 10 ℃, and stirring;
s2, adding butyl acetate into S1, adding an acetic acid solution under the stirring condition to adjust the pH value, wherein the time from the beginning of adding the acetic acid solution to the end of extraction is 15min, and the temperature of the solution is kept below 10 ℃ in the extraction process;
s3, standing and layering after extraction to obtain a butyl acetate layer;
s4, adding 0.01-0.03 time of 1,1,3, 3-tetramethylbutylamine into the butyl acetate layer, and stirring for 5-6 min;
s5, concentrating the solution obtained in the step S4 under reduced pressure until the solution becomes turbid and more precipitates are observed to be generated, then placing the solution in ice water for cooling and filtering, and soaking a filter cake with butyl acetate, washing and filtering;
s6, continuing carrying out vacuum filtration on the S5 filter cake until the filter cake is dry, adding fresh acetone, 1,3, 3-tetramethylbutylamine and purified water, heating to 30-35 ℃, continuously stirring for 2 hours, cooling in ice water, filtering slurry, and discarding mother liquor to obtain pravastatin 1,1,3, 3-tetramethylbutylamine wet powder;
s7, drying the pravastatin 1,1,3, 3-tetramethylbutylamine wet powder obtained in the S6 for 7-8 hours under the vacuum condition of 30-40 ℃ to obtain the high-purity pravastatin 1,1,3, 3-tetramethylbutylamine.
2. The method for preparing high purity pravastatin 1,1,3, 3-tetramethylbutylamine according to claim 1, wherein the volume of the purified water added in step S1 is 5 to 10 times of the mass of pravastatin sodium.
3. The method for preparing high purity pravastatin 1,1,3, 3-tetramethylbutylamine according to claim 1, wherein the amount of butyl acetate added in step S2 is 1 to 5 times the volume of the solution in step S1.
4. The method for preparing high-purity pravastatin 1,1,3, 3-tetramethylbutylamine according to claim 3, wherein butyl acetate in step S2 is precooled to below 10 ℃.
5. The method for preparing high-purity pravastatin 1,1,3, 3-tetramethylbutylamine according to claim 1, wherein the acetic acid solution added in step S2 has a mass concentration of 20 to 30% and a pH adjustment target value of 3.5 to 4.5.
6. The method for preparing high purity pravastatin 1,1,3, 3-tetramethylbutylamine according to claim 1, wherein the temperature of the concentration under reduced pressure in step S5 is not higher than 35 ℃.
7. The method for preparing high-purity pravastatin 1,1,3, 3-tetramethylbutylamine according to claim 1, wherein the butyl acetate soaking time in step S5 is 10-30 min.
8. The method for preparing high purity pravastatin 1,1,3, 3-tetramethylbutylamine according to claim 1, wherein the volume of fresh acetone added in step S6 is 4 to 8 times (v/w) the weight of the dry solid obtained by suction filtration.
9. The method for preparing high-purity pravastatin 1,1,3, 3-tetramethylbutylamine according to claim 1, wherein the volume ratio of fresh acetone, 1,3, 3-tetramethylbutylamine and purified water in step S6 is 4-8: 0.2: 0.1.
10. The purity of the pravastatin 1,1,3, 3-tetramethylbutylamine obtained by the preparation method according to any one of claims 1 to 9 is 99.791%, and the product is used as a standard product for detecting the content of pravastatin sodium and related substances.
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