A preparation method of rosuvastatin calcium intermediate

Abstract

The present invention relates to the field of organic synthesis technology, and in particular to a preparation method of rosuvastatin calcium intermediate. The method includes mixing a reactant, a photocatalyst and a first organic solvent to form a reaction system; the reaction system is catalytically reacted under visible light irradiation conditions and an air environment to obtain a target product; the molar amount of the photocatalyst is 5% to 15% of the molar amount of the reactant; the reactant is 6-(4-fluorophenyl)-1,2-dihydro-4-(1-methylethyl)-2-oxo-5-tetrahydropyrimidinecarboxylic acid methyl esters; the photocatalyst is a dye photocatalyst; the target product is 6-(4-fluorophenyl)-1,2-dihydro-4-(1-methylethyl)-2-oxo-5-pyrimidinecarboxylic acid methyl esters. The present invention can not only solve the environmental pollution problems and safety risk problems present in existing preparation methods, but also can prepare a target product in high yield.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and in particular to a method for preparing a rosuvastatin calcium intermediate. Background Art

[0002] Rosuvastatin calcium is a selective HMG-CoA reductase inhibitor, whose chemical name is bis-[(E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl](3R,5S)-3,5-dihydroxyhept-6-heptenoic acid] calcium salt.

[0003] Methyl 6-(4-fluorophenyl)-1,2-dihydro-4-(1-methylethyl)-2-oxo-5-pyrimidinecarboxylate is an important intermediate in the preparation of rosuvastatin calcium. Its structure is shown below:

[0004] .

[0005] In the prior art, the preparation method of methyl 6-(4-fluorophenyl)-1,2-dihydro-4-(1-methylethyl)-2-oxo-5-pyrimidinecarboxylate includes a concentrated nitric acid oxidation method. Specifically, this method uses excess concentrated nitric acid to oxidatively dehydrogenate methyl 4-(4-fluorophenyl)-6-isopropyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate to produce methyl 6-(4-fluorophenyl)-1,2-dihydro-4-(1-methylethyl)-2-oxo-5-pyrimidinecarboxylate. However, using concentrated nitric acid as an oxidant can cause environmental pollution and safety issues, and a large amount of base is required for neutralization during post-processing, resulting in a large amount of sodium nitrate waste liquid, which increases post-processing costs.

[0006] In the existing literature (Yingtao Zhou, Chenhui Lin, Yuzhi Xing, Ligong Chen, Xilong Yan. Efficient Construction of the Nucleus of Rosuvastatin Calcium. J. Heterocyclic Chem., (2017), 54, 1898), Zhou et al. used copper chloride, potassium carbonate, and aqueous tert-butyl hydroperoxide as an oxidant to prepare methyl 6-(4-fluorophenyl)-1,2-dihydro-4-(1-methylethyl)-2-oxo-5-pyrimidinecarboxylate. Compared to concentrated nitric acid oxidation, this method offers a higher yield and avoids the production of large amounts of sodium nitrate waste. However, the tert-butyl hydroperoxide used in this method is an organic peroxide, and its peroxide bond is highly susceptible to decomposition under light, heat, friction, or mechanical impact, generating oxygen-containing free radicals that trigger a series of chemical reactions. The generated heat can also cause fires and explosions. Therefore, the use of tert-butyl hydroperoxide in industrial production still poses a risk. In addition, leakage of tert-butyl hydroperoxide can cause serious pollution to water, soil and atmosphere.

[0007] In summary, it is necessary to develop a preparation method for rosuvastatin calcium intermediates to solve the environmental pollution problems and safety risks existing in the existing preparation methods. Summary of the Invention

[0008] The present invention aims to provide a method for preparing a rosuvastatin calcium intermediate, and the specific technical scheme is as follows:

[0009] In a first aspect, the present invention provides a method for preparing a rosuvastatin calcium intermediate, comprising mixing reactants, a photocatalyst, and a first organic solvent to form a reaction system; subjecting the reaction system to a catalytic reaction under visible light irradiation and an air environment to obtain a target product;

[0010] The molar amount of the photocatalyst is 5% to 15% of the molar amount of the reactant;

[0011] The amount of the first organic solvent used is 2-6 ml per gram of the reactant;

[0012] The reactant is methyl 6-(4-fluorophenyl)-1,2-dihydro-4-(1-methylethyl)-2-oxo-5-tetrahydropyrimidinecarboxylate;

[0013] The photocatalyst is a dye photocatalyst;

[0014] The target product is methyl 6-(4-fluorophenyl)-1,2-dihydro-4-(1-methylethyl)-2-oxo-5-pyrimidinecarboxylate.

[0015] Optionally, the dye photocatalyst includes at least one of eosin Y disodium salt and eosin B.

[0016] Optionally, the first organic solvent includes 1,4-dioxane.

[0017] Optionally, the reaction temperature used in the catalytic reaction is 20-35° C., and the reaction time used is 20-30 h.

[0018] Optionally, the catalytic reaction is carried out under stirring conditions; the stirring conditions include magnetic stirring.

[0019] Optionally, the preparation method of the rosuvastatin calcium intermediate further comprises post-processing the target product; the post-processing comprises performing a rotary evaporation treatment on the reaction solution containing the target product; and the rotary evaporation temperature used in the rotary evaporation treatment is 30-35°C.

[0020] Optionally, the post-treatment further includes alkalizing the target product after the rotary evaporation treatment; the alkalization treatment includes washing the target product with an alkaline solution; the alkaline solute used in the alkaline solution includes at least one of sodium hydroxide, potassium hydroxide, sodium carbonate and sodium bicarbonate; the pH value of the alkaline solution is 8~11.

[0021] Optionally, the post-treatment further includes performing a first extraction treatment on the target product after the alkalization treatment; the first extraction treatment includes using a second organic solvent to dissolve the target product to form a first extraction system; after the first extraction system is layered, the aqueous phase containing the target product is collected; the amount of the second organic solvent used is 3 to 8 ml of the second organic solvent per gram of target product; the second organic solvent includes dichloromethane.

[0022] Optionally, the post-treatment further comprises acidifying the target product after the extraction treatment; the acidifying treatment comprises washing the target product with an acid solution; the acid solution comprises a hydrochloric acid solution; and the pH value of the hydrochloric acid solution is ≤3;

[0023] The post-treatment also includes sequentially performing a second extraction treatment, a reduced pressure concentration treatment and a pulping treatment on the target product after the acidification treatment; the second extraction treatment includes using a third organic solvent to dissolve the target product to form a second extraction system; after the second extraction system is layered, the organic phase containing the target product is collected; the organic phase is then subjected to the reduced pressure concentration treatment, and then subjected to the pulping treatment to obtain the target product; the third organic solvent includes dichloromethane; the amount of the third organic solvent is 3~8ml of the third organic solvent per gram of target product; the reduced pressure pressure used in the reduced pressure concentration treatment is ≤-0.07MPa, and the concentration temperature used is 30~35℃; the pulping treatment includes rotary evaporation of the target product after the reduced pressure concentration treatment, followed by adding ethanol, stirring and pulping at 60~70℃ for 1~2h, and finally, reducing the temperature to 25~35℃ for filtration, and drying under reduced pressure to constant weight to obtain the target product; wherein, the drying temperature used in the reduced pressure drying is 50~55℃, and the reduced pressure used is <-0.08Mpa.

[0024] In a second aspect, the present invention provides a rosuvastatin calcium intermediate prepared by the preparation method of the rosuvastatin calcium intermediate, wherein the rosuvastatin calcium intermediate is 6-(4-fluorophenyl)-1,2-dihydro-4-(1-methylethyl)-2-oxo-5-pyrimidinecarboxylic acid methyl ester; the yield of the rosuvastatin calcium intermediate is greater than or equal to 87%, and the purity is greater than or equal to 99%.

[0025] The application of the technical solution of the present invention has at least the following beneficial effects:

[0026] (1) The present invention provides a method for preparing a rosuvastatin calcium intermediate, which can not only solve the environmental pollution and safety risk problems existing in existing preparation methods, but also can prepare the target product with high yield. Figure 1The present invention adopts 6-(4-fluorophenyl)-1,2-dihydro-4-(1-methylethyl)-2-oxo-5-tetrahydropyrimidinecarboxylic acid methyl ester as a reactant, adopts a dye photocatalyst, and mixes with a first organic solvent to form a reaction system. The reaction system is irradiated with visible light in an air environment, and the photocatalyst (abbreviated as PC) is excited by the visible light to an excited state PC*, and undergoes a HAT (i.e., hydrogen atom transfer) process with the reactant to produce an intermediate product I and an intermediate product PC-H•; subsequently, the intermediate product PC-H• forms a peroxyl free radical intermediate product III through the HAT process, and the intermediate product I undergoes tautomerism to form an intermediate product II; finally, the peroxyl free radical intermediate product III oxidizes the intermediate product II (i.e., a SET process occurs, SET represents single electron transfer) to obtain the target product 6-(4-fluorophenyl)-1,2-dihydro-4-(1-methylethyl)-2-oxo-5-pyrimidinecarboxylic acid methyl ester. The preparation method is simple to operate, operates under mild reaction conditions, and produces a yield of over 87% of the target product, making it suitable for mass production. Therefore, the preparation method of the present invention does not require the use of hazardous reagents such as concentrated nitric acid or tert-butyl hydroperoxide, effectively addressing the environmental pollution and safety risks associated with existing preparation methods.

[0027] (2) The target product prepared by the present invention not only has a yield of more than 87%, but also has a high purity, that is, a purity greater than or equal to 99%, and has good application value.

[0028] In addition to the above-described objects, features and advantages, the present invention has other objects, features and advantages. The present invention will be further described in detail below with reference to the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] The accompanying drawings, which constitute part of this application, are intended to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are intended to explain the present invention and do not constitute an undue limitation of the present invention. In the accompanying drawings:

[0030] Figure 1 This is a reaction principle diagram of a method for preparing a rosuvastatin calcium intermediate provided by the present invention;

[0031] Figure 2 This is the HPLC detection spectrum of the target product prepared in Example 1;

[0032] Figure 3 This is the HPLC detection spectrum of the target product prepared in Example 2;

[0033] Figure 4 The target product prepared in Example 1 1 H NMR detection spectrum;

[0034] Figure 5This is the mass spectrometry detection spectrum of the target product prepared in Example 1;

[0035] Among them, Figure 2 and Figure 3 In , “DAD” stands for photodiode array detector;

[0036] “DAD1 A” indicates the first wavelength set in the photodiode array detector;

[0037] “Sig” indicates the detection wavelength;

[0038] “Ref” indicates the reference wavelength;

[0039] “RT” indicates retention time;

[0040] “RRT” indicates relative retention time;

[0041] “Area” indicates peak area;

[0042] “Area%” indicates peak area percentage;

[0043] “High” indicates peak height;

[0044] “Weigh” indicates peak width;

[0045] “R” stands for separation;

[0046] “TF” indicates tailing factor;

[0047] “Plates” indicates the number of theoretical plates;

[0048] “S / N” means signal-to-noise ratio;

[0049] exist Figure 4 The horizontal axis represents the chemical shift in ppm; the vertical axis represents the absorption peak intensity;

[0050] exist Figure 5 The horizontal axis represents the mass-to-charge ratio of the ion; the vertical axis represents the relative abundance of the ion; wherein, the ion is the molecular ion or fragment ion generated by the target product sample losing its outer electron under the mass spectrometry detection conditions; Figure 5 The baseline that is approximately parallel to the horizontal axis is not unclear, but discontinuous, and the disconnected parts indicate that no signal is collected. DETAILED DESCRIPTION

[0051] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. All other embodiments obtained by ordinary technicians in this field based on the embodiments of the present invention are within the scope of protection of the present invention.

[0052] Example 1:

[0053] A method for preparing a rosuvastatin calcium intermediate comprises adding reactants, a photocatalyst, and a first organic solvent into a photoreactor tube and mixing them to form a reaction system; and subjecting the reaction system to a catalytic reaction under visible light irradiation and an air environment to obtain a target product.

[0054] The molar amount of the photocatalyst is 10% of the molar amount of the reactant; the molar amount of the reactant is 0.2 mmol;

[0055] The amount of the first organic solvent is 2-6 ml per gram of the reactant, and the specific amount is 3 ml / g of the reactant; the first organic solvent is 1,4-dioxane;

[0056] The reactant is methyl 6-(4-fluorophenyl)-1,2-dihydro-4-(1-methylethyl)-2-oxo-5-tetrahydropyrimidinecarboxylate;

[0057] The photocatalyst is a dye photocatalyst, specifically eosin Y disodium salt;

[0058] The target product is methyl 6-(4-fluorophenyl)-1,2-dihydro-4-(1-methylethyl)-2-oxo-5-pyrimidinecarboxylate.

[0059] The catalytic reaction adopts a reaction temperature of 20-35° C. (specifically 25° C.), and a reaction time of 20-30 h (specifically 24 h, the reaction time is determined by thin layer chromatography (TLC) method).

[0060] The catalytic reaction is completed under stirring conditions; the stirring conditions include magnetic stirring, specifically stirring with a magnetic stirring bar.

[0061] The preparation method further includes post-processing the target product, wherein the post-processing includes performing a rotary evaporation treatment on the reaction solution containing the target product; the rotary evaporation temperature used in the rotary evaporation treatment is 30-35°C (specifically 35°C).

[0062] The post-treatment further includes alkalizing the target product after the rotary evaporation treatment; the alkalization treatment includes washing the target product with an alkaline solution; the alkaline solute used in the alkaline solution includes at least one of sodium hydroxide, potassium hydroxide, sodium carbonate and sodium bicarbonate; the pH value of the alkaline solution is 8 to 11 (specifically, the pH value is 9).

[0063] The post-treatment further includes performing a first extraction treatment on the target product after the alkalization treatment; the first extraction treatment includes dissolving the target product in a second organic solvent to form a first extraction system; after the first extraction system is separated into layers, an aqueous phase containing the target product is collected (because the target product reacts with the alkali solution during the alkalization treatment to form a sodium salt that dissolves in water, the target product is contained in the aqueous phase); the amount of the second organic solvent used is 3 to 8 ml per gram of the target product, and the specific amount is 3 ml / g of the target product; the second organic solvent is dichloromethane.

[0064] The post-treatment further includes acidifying the target product after the extraction treatment; the acidifying treatment includes washing the target product with an acid solution; the acid solution includes a hydrochloric acid solution; the pH value of the hydrochloric acid solution is ≤3 (specifically, the pH value is 2);

[0065] The post-treatment further includes sequentially performing a second extraction treatment, a reduced pressure concentration treatment, and a pulping treatment on the target product after the acidification treatment; the second extraction treatment includes using a third organic solvent to dissolve the target product to form a second extraction system; after the second extraction system is layered, the organic phase containing the target product is collected (the sodium salt formed by the reaction of the target product with the alkali solution forms the target product dissolved in the organic phase after washing with acid solution, so the target product is contained in the organic phase); the organic phase is then subjected to the reduced pressure concentration treatment, and then subjected to the pulping treatment to obtain the target product; the third organic solvent is dichloromethane; the amount of the third organic solvent is per 3~8ml of the third organic solvent is used for each gram of the target product, and the specific amount is 3ml / g of the target product; the reduced pressure used in the reduced pressure concentration treatment is ≤-0.07MPa, specifically -0.09MPa, and the concentration temperature used is 30~35℃, specifically 30℃; the beating treatment includes rotary evaporation of the target product after the reduced pressure concentration treatment, and then adding ethanol, stirring and beating at 70℃ for 1h, and finally, cooling to 25℃ for filtration, and drying under reduced pressure to constant weight to obtain the target product; wherein, the drying temperature used in the reduced pressure drying is 50℃, and the reduced pressure used is -0.085Mpa.

[0066] Example 2:

[0067] The difference from Example 1 is that eosin Y disodium salt is replaced by eosin B.

[0068] Comparative Example 1:

[0069] The difference from Example 1 is that 1,4-dioxane is replaced by ethyl acetate.

[0070] Comparative Example 2:

[0071] The difference from Example 1 is that 1,4-dioxane is replaced by dichloromethane.

[0072] Comparative Example 3:

[0073] The difference from Example 1 is that 1,4-dioxane is replaced by toluene.

[0074] Comparative Example 4:

[0075] The difference from Example 1 is that Eosin Y disodium salt is replaced by Eosin.

[0076] Comparative Example 5:

[0077] The difference from Example 1 is that eosin Y disodium salt is replaced by fluorescein sodium.

[0078] Comparative Example 6:

[0079] The difference from Example 1 is that the photocatalyst was omitted. No target product was produced.

[0080] The target product prepared in Example 1 was sampled and tested by high performance liquid chromatography. 1 H NMR and mass spectrometry. Figure 2 and Figure 4~Figure 5 The HPLC test was performed using an Agilent HPLC instrument, model 1260. The HPLC test was used to determine the purity of the target product. The specific determination method is as follows:

[0081] Chromatographic column: Agilent XDB-C18, 4.6 mm (4.6 mm is the diameter of the chromatographic column) × 150 mm (150 mm is the length of the chromatographic column), 5 μm (5 μm is the particle size of the packing in the chromatographic column) or other similar packing columns;

[0082] Detection wavelength: 242 nm;

[0083] Flow rate: 1.0 ml / min;

[0084] Column temperature: 30°C;

[0085] Injection volume: 5µl;

[0086] Run time: 23 minutes;

[0087] Gradient elution was used, and the gradient elution table is as follows Table 1:

[0088] Table 1 Gradient elution table

[0089]

[0090] In Table 1, the preparation method of phase A is as follows: 1.0 ml of trifluoroacetic acid is transferred to 1000 ml of water, shaken well, and ultrasonicated to obtain phase A; phase B is chromatographically pure acetonitrile.

[0091] 1 H NMR was performed using a Bruker AVANCE III 400 MHz spectrometer and deuterated DMSO- d 6.

[0092] Mass spectrometry was performed using an Agilent mass spectrometer, specifically the LC1260-MS6120.

[0093] Depend on Figure 2 It is known that the purity of the target product prepared in Example 1 is 99.78%.

[0094] Depend on Figure 4 It is known that the data of the nuclear magnetic resonance hydrogen spectrum of the target product prepared in Example 1 are specifically:

[0095] 1 H NMR (400 MHz, DMSO-d6) δ 12.25 (s, 1H), 7.57 – 7.52 (m, 2H), 7.36– 7.30 (m, 2H), 3.55 (s, 3H), 3.09 (hept, J = 6.8 Hz, 1H), 1.22 (d, J = 6.8Hz, 6H).

[0096] The above data are consistent with those reported in existing literature (Yamamoto, K.; Chen, YG; Buono, FG Oxidative Dehydrogenation of Dihydropyrimidinones and Dihydropyrimidines. Org. Lett. 2005, 7, 4673-4676).

[0097] Depend on Figure 5 It is known that the mass spectrometry results of the target product prepared in Example 1 are [M + H + ] = 291.1, which is consistent with the calculated molecular weight of the target product of 291.1.

[0098] through Figure 4~Figure 5Analysis confirmed that the target product prepared in Example 1 was methyl 6-(4-fluorophenyl)-1,2-dihydro-4-(1-methylethyl)-2-oxo-5-pyrimidinecarboxylate.

[0099] The target products prepared in Examples 1-2 and Comparative Examples 1-5 were subjected to yield and purity determinations, respectively (Comparative Examples 1-5 were not subjected to purity determination due to low yields and lack of purity determination value). The determination results are shown in Table 2.

[0100] The yield determination method is as follows:

[0101] The yields of Examples 1 and 2 are actual isolated yields. Since the reaction effects of Comparative Examples 1-5 were not good, the yields were determined by the following method:

[0102] After the reaction and before post-processing, weigh 0.2 mmol of mesitylene trimethoxybenzene as an internal standard and add it to the target product. After the target product is fully dissolved, transfer it to a round-bottom flask and concentrate under reduced pressure (at -0.09 MPa and 55°C; it should be noted that the concentration temperature used in the yield determination in Comparative Example 2 was 30°C) to remove the solvent. Deuterated chloroform is then added and the product is transferred to an NMR tube. The yield is estimated based on the characteristic peak of the product at a chemical shift of approximately 1.44 ppm and the characteristic peak of mesitylene trimethoxybenzene at a chemical shift of approximately 6.10 ppm.

[0103] The purity of the target product prepared in Example 2 was determined in the same manner as in Example 1. For specific results, see Figure 3 .

[0104] Table 2 Yield and purity determination results

[0105]

[0106] According to the data in Table 2 and Figure 2~Figure 3 It can be seen that compared with Comparative Examples 1 to 5, the yields of the target products prepared using Examples 1 to 2 of the present invention are all greater than or equal to 87%, and the purities are all greater than 99%. This shows that using a suitable dye photocatalyst and a first organic solvent for the reactant 6-(4-fluorophenyl)-1,2-dihydro-4-(1-methylethyl)-2-oxo-5-tetrahydropyrimidinecarboxylic acid methyl ester is of great significance in improving the yield and purity of the target product.

[0107] Specifically, compared to Comparative Examples 1-3, it can be seen that the first organic solvent used in Examples 1-2 of the present invention is 1,4-dioxane, which can improve the yield and purity of the target product. This is because 1,4-dioxane can effectively dissolve the reactants and the target product, thereby improving the yield and purity of the target product under the action of the dye photocatalyst. While ethyl acetate used in Comparative Example 1 and toluene used in Comparative Example 3 can dissolve the reactants, they have poor solubility for the target product. The target product precipitates during the reaction, hindering the further advancement of the photoreaction, resulting in a low yield of the target product. The dichloromethane used in Comparative Example 2 has poor solubility for the reactants, resulting in fewer reactants participating in the reaction and a low yield of the target product.

[0108] Compared with Comparative Examples 4-5, it can be seen that the use of suitable dye photocatalysts in Examples 1-2 of the present invention can efficiently catalyze the reaction of reactants to generate target products, thereby improving the yield and purity of the target products.

[0109] The foregoing description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Those skilled in the art will readily appreciate that various modifications and variations of the present invention are possible. Any modifications, equivalent substitutions, or improvements made within the spirit and principles of the present invention are intended to be within the scope of protection of the present invention.

Claims

1. A method for preparing a rosuvastatin calcium intermediate, characterized in that: The method comprises mixing reactants, a photocatalyst and a first organic solvent to form a reaction system; and subjecting the reaction system to a catalytic reaction under visible light irradiation and an air environment to obtain a target product. The molar amount of the photocatalyst is 5% to 15% of the molar amount of the reactant; The amount of the first organic solvent used is 2-6 ml per gram of the reactant; The reactant is methyl 6-(4-fluorophenyl)-1,2-dihydro-4-(1-methylethyl)-2-oxo-5-tetrahydropyrimidinecarboxylate; the first organic solvent includes 1,4-dioxane; The photocatalyst is a dye photocatalyst; the dye photocatalyst includes at least one of eosin Y disodium salt and eosin B; The target product is methyl 6-(4-fluorophenyl)-1,2-dihydro-4-(1-methylethyl)-2-oxo-5-pyrimidinecarboxylate.

2. The method for preparing a rosuvastatin calcium intermediate according to claim 1, wherein The reaction temperature used in the catalytic reaction is 20-35° C., and the reaction time used is 20-30 h.

3. The method for preparing a rosuvastatin calcium intermediate according to claim 2, wherein The catalytic reaction is completed under stirring conditions; the stirring conditions include magnetic stirring.

4. The method for preparing a rosuvastatin calcium intermediate according to any one of claims 1 to 3, wherein: The method further includes post-processing the target product; the post-processing includes performing rotary evaporation on the reaction solution containing the target product; and the rotary evaporation temperature used in the rotary evaporation is 30-35°C.

5. The method for preparing a rosuvastatin calcium intermediate according to claim 4, wherein: The post-treatment further includes alkalizing the target product after the rotary evaporation treatment; the alkalization treatment includes washing the target product with an alkaline solution; the alkaline solute used in the alkaline solution includes at least one of sodium hydroxide, potassium hydroxide, sodium carbonate and sodium bicarbonate; the pH value of the alkaline solution is 8-11.

6. The method for preparing a rosuvastatin calcium intermediate according to claim 5, wherein: The post-treatment further includes performing a first extraction treatment on the target product after the alkalization treatment; the first extraction treatment includes using a second organic solvent to dissolve the target product to form a first extraction system; after the first extraction system is separated into layers, an aqueous phase containing the target product is collected; the amount of the second organic solvent used is 3 to 8 ml of the second organic solvent per gram of the target product; and the second organic solvent includes dichloromethane.

7. The method for preparing a rosuvastatin calcium intermediate according to claim 6, wherein: The post-treatment further includes acidifying the target product after the extraction treatment; the acidifying treatment includes washing the target product with acid solution; the acid solution includes hydrochloric acid solution; the pH value of the hydrochloric acid solution is ≤3.

8. The method for preparing a rosuvastatin calcium intermediate according to claim 7, wherein: The post-treatment further includes sequentially subjecting the target product after the acidification treatment to a second extraction treatment, a reduced pressure concentration treatment, and a pulping treatment; the second extraction treatment includes dissolving the target product in a third organic solvent to form a second extraction system; after the second extraction system is separated into layers, an organic phase containing the target product is collected; and the organic phase is subjected to the reduced pressure concentration treatment and then to the pulping treatment to obtain the target product; The third organic solvent includes dichloromethane; the amount of the third organic solvent is 3~8ml of the third organic solvent per gram of target product; the reduced pressure used in the reduced pressure concentration treatment is ≤-0.07MPa, and the concentration temperature used is 30~35℃; the beating treatment includes rotary evaporation of the target product after the reduced pressure concentration treatment, followed by adding ethanol, stirring and beating at 60~70℃ for 1~2h, and finally, reducing the temperature to 25~35℃ for filtration, and drying under reduced pressure to constant weight to obtain the target product; wherein, the drying temperature used in the reduced pressure drying is 50~55℃, and the reduced pressure used is <-0.08Mpa.

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