CN112521375A - Preparation method of rosuvastatin calcium intermediate - Google Patents
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- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
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Abstract
The invention belongs to the technical field of drug synthesis, and particularly relates to a preparation method of a rosuvastatin calcium intermediate; the method comprises the following steps: under the protection of inert gas, dissolving SM-1 in an organic solvent, adding alkali, tri- (3, 6-dioxaheptyl) amine and crown ether, stirring for half an hour, slowly adding SM-2, controlling the temperature to react, cooling the reaction liquid to room temperature after the reaction is finished, concentrating the filtrate under reduced pressure to dryness, adding a crystallization solvent, cooling and crystallizing, finishing crystallization, filtering, and drying to obtain a target product, namely a rosuvastatin calcium intermediate shown in a formula I; compared with the prior art, the method has the advantages of simple operation, higher yield and higher purity; by adding tri- (3, 6-dioxaheptyl) amine and crown ether in the reaction, the generation of Z-type isomers is avoided, the reaction condition is milder, ultralow temperature (-78 ℃) and n-butyl lithium and other compounds are avoided, the method is economical and environment-friendly, and is suitable for industrial production.
Description
Technical Field
The invention belongs to the technical field of medicine synthesis, and particularly relates to a preparation method of a rosuvastatin calcium intermediate.
Background
Research shows that rosuvastatin calcium serving as an HMG-CoA inhibitor is used for treating cardiovascular diseases, has the characteristics of strong effect, high safety, less side effect and good tolerance, plays an important role in reducing cardiovascular disease risk, and is prepared by using rosuvastatin calcium key intermediate 6- [ (1E) -2- [4- (4-fluorophenyl) -6-isopropyl-2- [ methyl (methylsulfonyl) amino ] - 5-pyrimidine ] ethenyl ] -2, 2-dimethyl-1, 3-dioxane-4-acetic acid alkyl ester having the following structural formula:
wherein R is selected from an alkyl group having 1 to 6 carbon atoms or an aryl group having 6 to 12 carbon atoms.
In patent WO0185702, applied to astrazeneca, uk, it is first proposed to perform Wittig (Wittig) condensation by forming the core into a phosphonium salt and the side chain of the tert-butyl ester into an aldehyde, to obtain a rosuvastatin skeleton, the synthesis steps being as follows:
the method needs to be carried out at the ultralow temperature of-78 ℃, and in addition, the final yield is very low, the synthesis cost is higher, and the method is not suitable for industrial production.
In addition, patents US2005/0124639a1, US2005/124639, WO2004/103977, US2012136151, US2004/49036, WO0049014 and the like all report that an olefination reaction is carried out through a mother nucleus quaternary phosphonium salt and an aldehyde side chain to obtain an E-type key intermediate compound, all relate to Wittig (Wittig) reaction, ultralow temperature reaction is required at-78 ℃, bases such as NaHMDS, n-butyl lithium and the like are consumed, the yield is not high, the environment is not friendly, meanwhile, a large amount of by-product diphenyl metaphosphoric acid is generated, and the obtained product contains Z-type isomer impurities and is difficult to remove.
CN103420919 tert-butyl (4R,6S) -6- [ (1E) -2- [4- (4-fluorophenyl) -6-isopropyl-2- [ methyl (methylsulfonyl) amino ] -5-pyrimidine ] vinyl ] -2, 2-dimethyl-1, 3-dioxane-4-acetate was synthesized by the method of the following formula.
The method needs to control the reaction at-70 ℃, has harsh conditions and 34 percent of yield, and is not suitable for industrial production.
The process for synthesizing rosuvastatin calcium intermediates IN patents IN2009MU03028, CN102617481, IN 2012CH02127, WO2011132172 and the like is tedious, low IN yield, harsh IN conditions and not friendly to the environment. Therefore, the research of a rosuvastatin calcium intermediate process method which is simpler, convenient, high in yield, low in Z-isomer content and environment-friendly is still a problem to be solved at present.
Disclosure of Invention
In order to make rosuvastatin calcium more suitable for industrial production, the invention provides a preparation method of a rosuvastatin calcium intermediate.
The specific technical scheme of the invention is as follows:
the method specifically comprises the following steps:
under the protection of inert gas, dissolving SM-1 in an organic solvent, adding alkali, tri- (3, 6-dioxaheptyl) amine (TDA-1) and crown ether, stirring for half an hour, slowly adding SM-2, controlling the temperature to react, after the reaction is finished, cooling the reaction liquid to room temperature, extracting an organic phase, concentrating under reduced pressure until the organic phase is dry, adding a crystallization solvent, cooling for crystallization, after the crystallization is finished, filtering, and drying to obtain the target product, namely the rosuvastatin calcium intermediate shown in the formula I.
Preferably, the organic solvent in step (a) is one or a combination of dimethyl sulfoxide, tetrahydrofuran, N-dimethylformamide, N-methylpyrrolidone, acetonitrile and toluene, wherein toluene is particularly preferred, and the added organic solvent is a reaction complete amount.
Preferably, the base in step (a) is one of potassium carbonate, potassium bicarbonate, potassium ethoxide, potassium tert-butoxide, potassium bis (trimethylsilyl) amide or a combination thereof, with potassium carbonate being particularly preferred.
Preferably, the crown ether in step (a) is one of 18-crown-6, 15-crown-5, 18-crown-6, dicyclohexyl-18-crown-6, diphenyl-18-crown-6 or a combination thereof, wherein 18-crown-6 is particularly preferred.
Preferably, the feeding molar ratio of SM-1 to SM-2 in the step is 1: 1.1 to 1.5, wherein 1: 1.2.
preferably, the molar ratio of SM-1 to base charged in step (a) is 1: 1.5 to 2.5, wherein 1: 2.
preferably, the charging molar ratio of the SM-1, the TDA-1 and the crown ether in the step is 1: 0.02-0.08: 0.05 to 0.15, and particularly preferably 1: 0.05: 0.1.
preferably, the crystallization solvent in step (a) is one of toluene, p-xylene, benzene or a combination thereof, wherein toluene is particularly preferred.
Preferably, the reaction temperature in the step is 20-60 ℃, and preferably 30-35 ℃.
Preferably, the reaction time in the step is 1-4 h.
The invention has the technical effects that:
1. the invention provides a preparation method of an important rosuvastatin calcium intermediate, which is simple to operate, high in yield (86%) and high in purity (99.70%).
2. By adding TDA-1 and crown ether in the reaction, the production of Z-type isomers is avoided, the reaction condition is milder, the use of ultralow temperature (-78 ℃) and n-butyl lithium and other compounds is avoided, the method is economical, environment-friendly and pollution-free, and is suitable for industrial production.
Detailed Description
The invention is further illustrated by the following examples, which should be properly understood: the examples of the present invention are provided for illustration only and not for limiting the present invention, and therefore, the simple modification of the present invention based on the method of the present invention is within the scope of the present invention as claimed.
The invention adopts HPLC to measure the purity of I, and the chromatographic conditions are as follows: [ column for chromatography: ultimate XB-C18(4.6 mm. times.150 mm, 3.0 μm); mobile phase A: 0.02% aqueous trifluoroacetic acid; mobile phase B: methanol: acetonitrile (1:1), gradient elution (0 → 30 min: B15% → 50%; 30 → 50 min: B50% → 80%; 50 → 60 min: B80% → 15%); column temperature: 40 ℃; detection wavelength: 216 nm; flow rate: 1.0 mL/min-1(ii) a Sample introduction amount: 10 μ L]。
Example 1
Under the protection of inert gas, 4- (4-fluorophenyl) -5-tributyl phosphonium bromide-6-isopropyl-2- [ (N-methyl-N-methanesulfonamido) ] -pyrimidine (SM-1, 6.18g, 0.01mol) is added into toluene (60mL), potassium carbonate (2.76g, 0.02mol), TDA-1(0.16g, 0.0005mol), 18-crown-6 (0.26g, 0.001mol) is added, stirring is carried out for 30min, (4R-cis) -6-aldehyde-2, 2-dimethyl-1, 3-dioxane-4-tert-butyl acetate (SM-2, 3.10g, 0.012mol) is slowly added, stirring is carried out for reaction for 2h at the temperature of 30-35 ℃, after TLC detection reaction is finished, the reaction liquid is cooled to room temperature and is filtered, concentrating the filtrate under reduced pressure to dryness, adding toluene (30mL), heating in water bath until the solid is completely dissolved, slowly cooling to 0-5 ℃, stirring for crystallization, performing suction filtration, and drying in vacuum to obtain the rosuvastatin calcium intermediate of the formula I, wherein the yield is 92.6%, and the purity is 99.90%.
Example 2
Under the protection of inert gas, 4- (4-fluorophenyl) -5-tributyl phosphonium bromide-6-isopropyl-2- [ (N-methyl-N-methanesulfonamide) ] -pyrimidine (SM-1, 6.18g, 0.01mol) is added into toluene (60mL), potassium carbonate (2.76g, 0.02mol), TDA-1(0.16g, 0.0005mol), 18-crown-6 (0.26g, 0.001mol) is added, stirring is carried out for 30min, (4R-cis) -6-aldehyde-2, 2-dimethyl-1, 3-dioxane-4-tert-butyl acetate (SM-2, 3.87g, 0.015mol) is slowly added, stirring is carried out at the temperature of 30-35 ℃ for reaction for 2h, after TLC detection reaction is finished, the reaction liquid is cooled to room temperature and filtered, concentrating the filtrate under reduced pressure to dryness, adding toluene (30mL), heating in water bath until the solid is completely dissolved, slowly cooling to 0-5 ℃, stirring for crystallization, performing suction filtration, and drying in vacuum to obtain the rosuvastatin calcium intermediate of the formula I, wherein the yield is 90.1%, and the purity is 99.87%.
Example 3
Under the protection of inert gas, 4- (4-fluorophenyl) -5-tributyl phosphonium bromide-6-isopropyl-2- [ (N-methyl-N-methanesulfonamido) ] -pyrimidine (SM-1, 6.18g, 0.01mol) is added into toluene (60mL), potassium carbonate (2.76g, 0.02mol), TDA-1(0.16g, 0.0005mol), 18-crown-6 (0.26g, 0.001mol) is added, stirring is carried out for 30min, slowly (4R-cis) -6-aldehyde-2, 2-dimethyl-1, 3-dioxane-4-tert-butyl acetate (SM-2, 2.84g, 0.011mol) is added, stirring is carried out at the temperature of 30-35 ℃ for 2h, after TLC detection reaction is finished, the reaction liquid is cooled to room temperature and filtered, concentrating the filtrate under reduced pressure to dryness, adding toluene (30mL), heating in water bath until the solid is completely dissolved, slowly cooling to 0-5 ℃, stirring for crystallization, performing suction filtration, and drying in vacuum to obtain the rosuvastatin calcium intermediate of the formula I, wherein the yield is 89.8%, and the purity is 99.85%.
Example 4
Under the protection of inert gas, 4- (4-fluorophenyl) -5-tributyl phosphonium bromide-6-isopropyl-2- [ (N-methyl-N-methanesulfonamide) ] -pyrimidine (SM-1, 6.18g, 0.01mol) is added into toluene (60mL), potassium carbonate (2.76g, 0.02mol), TDA-1(0.16g, 0.0005mol), 18-crown-6 (0.26g, 0.001mol) is added, stirring is carried out for 30min, (4R-cis) -6-aldehyde-2, 2-dimethyl-1, 3-dioxane-4-tert-butyl acetate (SM-2, 4.39g, 0.017mol) is slowly added, stirring is carried out at the temperature of 30-35 ℃ for reaction for 2h, after TLC detection reaction is finished, the reaction liquid is cooled to room temperature and filtered, concentrating the filtrate under reduced pressure to dryness, adding toluene (30mL), heating in water bath until the solid is completely dissolved, slowly cooling to 0-5 ℃, stirring for crystallization, performing suction filtration, and drying in vacuum to obtain the rosuvastatin calcium intermediate of the formula I, wherein the yield is 89.7%, and the purity is 99.84%.
Example 5
Under the protection of inert gas, 4- (4-fluorophenyl) -5-tributyl phosphonium bromide-6-isopropyl-2- [ (N-methyl-N-methanesulfonamide) ] -pyrimidine (SM-1, 6.18g, 0.01mol) is added into toluene (60mL), potassium carbonate (2.76g, 0.02mol), TDA-1(0.16g, 0.0005mol), 18-crown-6 (0.26g, 0.001mol) is added, stirring is carried out for 30min, (4R-cis) -6-aldehyde-2, 2-dimethyl-1, 3-dioxane-4-tert-butyl acetate (SM-2, 1.81g, 0.007mol) is slowly added, stirring is carried out at the temperature of 30-35 ℃ for reaction for 2h, after TLC detection reaction is finished, the reaction liquid is cooled to room temperature and filtered, concentrating the filtrate under reduced pressure to dryness, adding toluene (30mL), heating in water bath until the solid is completely dissolved, slowly cooling to 0-5 ℃, stirring for crystallization, performing suction filtration, and drying in vacuum to obtain the rosuvastatin calcium intermediate of the formula I, wherein the yield is 89.3%, and the purity is 99.84%.
Example 6
Under the protection of inert gas, 4- (4-fluorophenyl) -5-tributyl phosphonium bromide-6-isopropyl-2- [ (N-methyl-N-methanesulfonamide) ] -pyrimidine (SM-1, 6.18g, 0.01mol) is added into toluene (60mL), potassium carbonate (2.07g, 0.015mol), TDA-1(0.064g, 0.0002mol), 18-crown-6 (0.39g, 0.0015mol) is added, stirring is carried out for 30min, 4R-cis) -6-aldehyde-2, 2-dimethyl-1, 3-dioxane-4-acetic acid tert-butyl ester (SM-2, 2.84g, 0.011mol) is slowly added, stirring is carried out for reaction for 2h at the temperature of 30-35 ℃, after TLC detection reaction is finished, the reaction liquid is cooled to room temperature and filtered, concentrating the filtrate under reduced pressure to dryness, adding toluene (30mL), heating in water bath until the solid is completely dissolved, slowly cooling to 0-5 ℃, stirring for crystallization, performing suction filtration, and drying in vacuum to obtain the rosuvastatin calcium intermediate of the formula I, wherein the yield is 87.4%, and the purity is 99.73%.
Example 7
Under the protection of inert gas, 4- (4-fluorophenyl) -5-tributyl phosphonium bromide-6-isopropyl-2- [ (N-methyl-N-methanesulfonamido) ] -pyrimidine (SM-1, 6.18g, 0.01mol) is added into toluene (60mL), potassium carbonate (3.45g, 0.025mol), TDA-1(0.256g, 0.0008mol), 18-crown-6 (0.13g, 0.0005mol) is added, stirred for 30min, slowly added with (4R-cis) -6-aldehyde-2, 2-dimethyl-1, 3-dioxane-4-acetic acid tert-butyl ester (SM-2, 2.84g, 0.011mol), stirred for 2h at the temperature of 30-35 ℃, after TLC detection reaction is finished, the reaction liquid is cooled to room temperature and filtered, concentrating the filtrate under reduced pressure to dryness, adding toluene (30mL), heating in water bath until the solid is completely dissolved, slowly cooling to 0-5 ℃, stirring for crystallization, performing suction filtration, and drying in vacuum to obtain the rosuvastatin calcium intermediate of the formula I, wherein the yield is 87.2%, and the purity is 99.71%.
Example 8
Under the protection of inert gas, 4- (4-fluorophenyl) -5-tributyl phosphonium bromide-6-isopropyl-2- [ (N-methyl-N-methanesulfonamide) ] -pyrimidine (SM-1, 6.18g, 0.01mol) is added into toluene (60mL), potassium carbonate (2.07g, 0.015mol), TDA-1(0.256g, 0.0008mol), 18-crown-618-crown-6 (0.39g, 0.0015mol) is added, stirring is carried out for 30min, 4R-cis) -6-aldehyde-2, 2-dimethyl-1, 3-dioxane-4-acetic acid tert-butyl ester (SM-2, 3.87g, 0.015mol) is slowly added, the temperature is controlled to 30-35 ℃, stirring reaction is carried out for 2h, after TLC detection reaction, the reaction liquid is cooled to room temperature, and (3) carrying out suction filtration, concentrating the filtrate under reduced pressure to dryness, adding toluene (30mL), heating in a water bath until the solid is completely dissolved, slowly cooling to 0-5 ℃, stirring and crystallizing, carrying out suction filtration, and carrying out vacuum drying to obtain the rosuvastatin calcium intermediate of the formula I, wherein the yield is 86.8%, and the purity is 99.70%.
Example 9
Under the protection of inert gas, 4- (4-fluorophenyl) -5-tributyl phosphonium bromide-6-isopropyl-2- [ (N-methyl-N-methanesulfonamido) ] -pyrimidine (SM-1, 6.18g, 0.01mol) is added into toluene (60mL), potassium carbonate (2.76g, 0.02mol), TDA-1(0.16g, 0.0005mol), 18-crown-6 (0.26g, 0.001mol) is added, stirring is carried out for 30min, slowly (4R-cis) -6-aldehyde-2, 2-dimethyl-1, 3-dioxane-4-tert-butyl acetate (SM-2, 2.84g, 0.011mol) is added, stirring is carried out at the temperature of 30-35 ℃ for 2h, after TLC detection reaction is finished, the reaction liquid is cooled to room temperature and filtered, concentrating the filtrate under reduced pressure to dryness, adding toluene (30mL), heating in water bath until the solid is completely dissolved, slowly cooling to 0-5 ℃, stirring for crystallization, performing suction filtration, and drying in vacuum to obtain the rosuvastatin calcium intermediate of the formula I, wherein the yield is 86.5%, and the purity is 99.72%.
Example 10
Under the protection of inert gas, adding 4- (4-fluorophenyl) -5-tributyl phosphonium bromide-6-isopropyl-2- [ (N-methyl-N-methanesulfonamide) ] -pyrimidine (SM-1, 6.18g, 0.01mol) into dimethyl sulfoxide (50mL), adding potassium bicarbonate (2.00g, 0.02mol), TDA-1(0.16g, 0.0005mol), 15-crown-5 (0.22g, 0.001mol), stirring for 30min, slowly adding (4R-cis) -6-aldehyde-2, 2-dimethyl-1, 3-dioxane-4-acetic acid tert-butyl ester (SM-2, 2.84g, 0.011mol), stirring for reaction at the temperature of 60-65 ℃ for 1h, after TLC detection reaction, cooling the reaction liquid to room temperature, and (3) carrying out suction filtration, concentrating the filtrate under reduced pressure to dryness, adding toluene (30mL), heating in a water bath until the solid is completely dissolved, slowly cooling to 0-5 ℃, stirring and crystallizing, carrying out suction filtration, and carrying out vacuum drying to obtain the rosuvastatin calcium intermediate of the formula I, wherein the yield is 84.8%, and the purity is 99.75%.
Example 11
Under the protection of inert gas, adding 4- (4-fluorophenyl) -5-tributyl phosphonium bromide-6-isopropyl-2- [ (N-methyl-N-methanesulfonamide) ] -pyrimidine (SM-1, 6.18g, 0.01mol) into tetrahydrofuran (80mL), adding sodium ethoxide (1.36g, 0.02mol), TDA-1(0.16g, 0.0005mol), dicyclohexyl-18-crown-6 (0.37g, 0.001mol), stirring for 30min, slowly adding (4R-cis) -6-aldehyde-2, 2-dimethyl-1, 3-dioxane-4-acetic acid tert-butyl ester (SM-2, 2.84g, 0.011mol), stirring for reaction for 4h at the temperature of 20-25 ℃, cooling the reaction liquid to room temperature after TLC detection reaction, and (3) carrying out suction filtration, concentrating the filtrate under reduced pressure to dryness, adding benzene (60mL), heating in a water bath until the solid is completely dissolved, slowly cooling to 0-5 ℃, stirring and crystallizing, carrying out suction filtration, and carrying out vacuum drying to obtain the rosuvastatin calcium intermediate of the formula I, wherein the yield is 86.2%, and the purity is 99.70%.
Example 12
Under the protection of inert gas, adding 4- (4-fluorophenyl) -5-tributyl phosphonium bromide-6-isopropyl-2- [ (N-methyl-N-methanesulfonamide) ] -pyrimidine (SM-1, 6.18g, 0.01mol) into N, N-dimethylformamide (50mL), adding sodium tert-butoxide (1.92g, 0.02mol), TDA-1(0.16g, 0.0005mol), dibenzo-18-crown-6 (0.36g, 0.001mol), stirring for 30min, slowly adding (4R-cis) -6-aldehyde-2, 2-dimethyl-1, 3-dioxane-4-acetic acid tert-butyl ester (SM-2, 2.84g, 0.011mol), stirring for reaction for 2h at the temperature of 45-50 ℃, after TLC detection reaction is finished, cooling the reaction liquid to room temperature, carrying out suction filtration, concentrating the filtrate under reduced pressure to dryness, adding benzene (80mL), heating in a water bath until the solid is completely dissolved, slowly cooling to 0-5 ℃, stirring for crystallization, carrying out suction filtration, and carrying out vacuum drying to obtain the rosuvastatin calcium intermediate shown in the formula I, wherein the yield is 84.4%, and the purity is 99.73%.
Example 13
Under the protection of inert gas, adding 4- (4-fluorophenyl) -5-tributyl phosphonium bromide-6-isopropyl-2- [ (N-methyl-N-methanesulfonamide) ] -pyrimidine (SM-1, 6.18g, 0.01mol) into acetonitrile (50mL), adding potassium bis (trimethylsilyl) amide (3.99 g, 0.02mol), TDA-1(0.16g, 0.0005mol), dicyclohexyl-18-crown-6 (0.37g, 0.001mol), stirring for 30min, slowly adding (4R-cis) -6-aldehyde-2, 2-dimethyl-1, 3-dioxane-4-acetic acid tert-butyl ester (SM-2, 2.84g, 0.011mol), stirring for reaction for 2h at the temperature of 70-75 ℃, after TLC detection reaction is finished, and cooling the reaction solution to room temperature, carrying out suction filtration, concentrating the filtrate under reduced pressure to dryness, adding p-xylene (60mL), heating in a water bath until the solid is completely dissolved, slowly cooling to 0-5 ℃, stirring, crystallizing, carrying out suction filtration, and carrying out vacuum drying to obtain the rosuvastatin calcium intermediate shown in the formula I, wherein the yield is 83.8%, and the purity is 99.75%.
Comparative examples
A mixture of Z-8(19.17g) and THF (227mL) was brought to 40 ℃ until the solution was clear and the mixture was cooled to-75 ℃ under nitrogen. Sodium bis (trimethylsilyl) amide (37.4mL of 1.0M solution in THF) was added to the reaction mixture over 10 minutes to form a red anion solution. Stirring was carried out at constant temperature for 1 hour until a red suspension was formed. D-7(80mL) was slowly added dropwise to the suspension at-73 ℃ and then stirred at constant temperature for 15 minutes. After the reaction was complete, the temperature was raised to 10 ℃. Glacial acetic acid (3.21g) was added and stirred for 5 min. Distilling under normal pressure, and collecting distillate. The concentrated mixture was cooled, extracted with water (40 ml. times.3), and the organic phase was collected. Concentrating, vacuum distilling, and vacuum drying to obtain R-1. Acetonitrile (55g) was added to a water bath temperature-controlled nitrogen-protected light-shielded reaction flask, and R-1(10g) was added. Heating to 35-40 ℃, dropwise adding hydrochloric acid (19mL, 0.02M), reacting at constant temperature for 2-4 hours, detecting by TLC that R-1 basically disappears, extracting by ethyl acetate (200mL) after the reaction is finished, and recrystallizing by toluene to obtain R-2, wherein the yield is 34%, and the purity is 99.62%.
Claims (10)
1. A preparation method of a rosuvastatin calcium intermediate is characterized in that SM-1 and SM-2 react to obtain the rosuvastatin calcium intermediate shown in the formula I; the reaction route is as follows:
2. the preparation method according to claim 1, characterized in that the method comprises the following steps,
under the protection of inert gas, dissolving SM-1 in an organic solvent, adding alkali, tri- (3, 6-dioxaheptyl) amine, crown ether and SM-2, controlling the temperature to react, cooling the reaction liquid to room temperature after the reaction is finished, concentrating the filtrate under reduced pressure to dryness, adding a crystallization solvent, cooling and crystallizing, finishing crystallization, filtering, and drying to obtain the target product, namely the rosuvastatin calcium intermediate shown in the formula I.
3. The preparation method of claim 2, wherein the base is one or a combination of potassium carbonate, potassium bicarbonate, sodium ethoxide, sodium tert-butoxide, potassium bis (trimethylsilyl) amide.
4. The method according to claim 2, wherein the organic solvent is one or a combination of dimethyl sulfoxide, tetrahydrofuran, N-dimethylformamide, N-methylpyrrolidone, acetonitrile and toluene.
5. The method according to claim 2, wherein the crown ether is one of 18-crown-6, 15-crown-5, dicyclohexyl-18-crown-6, dibenzo-18-crown-6, or a combination thereof.
6. The method according to claim 2, wherein the molar ratio of SM-1 to SM-2 is 1: 1.1 to 1.5.
7. The process according to claim 2, wherein the molar ratio of SM-1 to base is 1: 1.5 to 2.5.
8. The method according to claim 2, wherein the molar ratio of SM-1, TDA-1 and crown ether is 1: 0.02-0.08: 0.05 to 0.15.
9. The method according to claim 2, wherein the crystallization solvent is one of toluene, p-xylene, benzene or a combination thereof.
10. The method according to claim 2, wherein the reaction temperature in the step (A) is 20 to 60 ℃.
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