Preparation method of varenicline tartrate intermediate

Abstract

The invention belongs to the technical field of chemical medicine raw material medicine and preparation manufacturing, and particularly relates to a preparation method of a varenicline tartrate intermediate. According to the present invention, 2, 3, 4, 5-tetrahydro-7, 8-dinitro-3-(trifluoroacetyl)-1, 5-methylene-1H-3-benzaza is adopted as a raw material, and the 2, 3, 4, 5-tetrahydro-7, 8-diamino-3-(trifluoroacetyl)-1, 5-methylene-1H-3-benzaza is prepared through the reduction of disulfurous acid or a salt thereof, such that the method does not need to use hydrogen pressurization, can be used for preparing the 2, 3, 4, 5-tetrahydro-7, 8-diamino-3-(trifluoroacetyl)-1, 5-methylene-1H-3-benzaza, and can be used for preparing the 2, 3, 4, 5-tetrahydro-7, 8-diamino-3-(trifluoroacetyl)-1, 5- meanwhile, the use of heavy metal palladium is avoided, the reaction condition is mild, the cost is low, the target product yield is high (greater than 75%), the purity is excellent (greater than 97%), and the industrial production of varenicline tartrate is facilitated.

Description

Technical Field

[0001] This invention belongs to the field of chemical pharmaceutical raw material and formulation manufacturing technology. More specifically, it relates to a method for preparing varenicline tartrate intermediate. Background Technology

[0002] Varenicline tartrate is an important non-nicotine smoking cessation medication. As a partial agonist of nicotine acetylcholine receptors, it not only mimics the binding of nicotine to its receptors to alleviate withdrawal symptoms but also blocks the complete binding of nicotine to the receptors, thereby reducing the euphoric effects of smoking. Clinical studies have shown that varenicline tartrate has advantages such as stable efficacy, few side effects, and a low relapse rate, and its efficacy is significantly superior to many conventional smoking cessation medications, making it of significant value in the field of smoking cessation treatment.

[0003] 2,3,4,5-Tetrahydro-7,8-diamino-3-(trifluoroacetyl)-1,5-methylene-1H-3-benzodiazepine is a key intermediate in the synthesis of varenicline tartrate (patents CN116725967A and CN1509174A). It possesses a 7,8-diamino structure and undergoes further intramolecular cyclization in subsequent reactions to construct the core structure of varenicline tartrate. Therefore, the synthesis efficiency and purity of this intermediate directly affect the smooth progress of subsequent reactions and the yield of the final product, varenicline tartrate.

[0004] Early synthesis processes for this intermediate used hydrogen as a reducing agent and required pressurized conditions. Although subsequent studies introduced Raney nickel catalysts to attempt improvements, the reaction still relied on hydrogen pressurization, and the highly reactive nature of Raney nickel resulted in a high risk of explosion. To mitigate the risks associated with hydrogen pressurization, researchers gradually explored reduction methods that did not require it. One study used ammonium formate as a hydrogen donor to synthesize the intermediate using noble metal catalysts such as palladium on carbon or palladium hydroxide. However, palladium-based catalysts are not only expensive, but the residue and emission of the heavy metal palladium pose potential environmental hazards, contradicting the principles of green chemistry.

[0005] Therefore, there is an urgent need to develop a synthesis method that can achieve high yield and high purity of the product without relying on hydrogen pressurization and precious metal palladium catalyst. Summary of the Invention

[0006] This invention addresses the shortcomings of existing methods for synthesizing varenicline tartrate intermediates—2,3,4,5-tetrahydro-7,8-diamino-3-(trifluoroacetyl)-1,5-methylene-1H-3-benzodiazepine—which rely on pressurized hydrogen and a noble metal palladium catalyst, resulting in high explosion risks and high costs. The invention aims to provide a method for preparing varenicline tartrate intermediates.

[0007] The above-mentioned objective of this invention is achieved through the following technical solution: This invention protects a method for preparing a varenicline tartrate intermediate, comprising the following steps: The compound shown in Formula II is reduced with dithionite or its salt in the presence of a solvent to obtain the varenicline tartrate intermediate: ; The solvent is a combination of water and an organic solvent, wherein the organic solvent is selected from methanol and / or ethanol.

[0008] This invention creatively discovers that by using dithionite or its salt to reduce the compound shown in Formula II to prepare the compound shown in Formula I, high yield (>75%) and high purity (>97%) products can be obtained without the use of hydrogen pressurization and without the use of the precious metal palladium. The reaction conditions are mild, the process is safe, and the cost is low, which is beneficial to the industrial production of varenicline tartrate.

[0009] Preferably, the molar ratio of the compound represented by Formula II to dithionite or its salt is 1:(5~15).

[0010] Furthermore, the molar ratio of the compound shown in Formula II to dithionite or its salt is 1:(6~12).

[0011] More preferably, the molar ratio of the compound represented by Formula II to dithionite or its salt is 1:(8~12).

[0012] Most preferably, the molar ratio of the compound represented by Formula II to dithionite or its salt is 1:10.

[0013] Preferably, the salt in the dithionite or its salt includes one of sodium dithionite, potassium dithionite, zinc dithionite, and calcium dithionite.

[0014] Furthermore, the salt in the dithionite or its salt is sodium dithionite.

[0015] Preferably, the volume-to-mass ratio of the organic solvent to the compound of formula II is (5~15) mL:1 g.

[0016] Furthermore, the volume-to-mass ratio of the organic solvent to the compound shown in Formula II is (6~12) mL:1 g.

[0017] More preferably, the volume-to-mass ratio of the organic solvent to the compound of formula II is (8~12) mL:1 g.

[0018] Most preferably, the volume-to-mass ratio of the organic solvent to the compound of formula II is (10~12) mL:1 g.

[0019] Preferably, the volume ratio of water to organic solvent is 1:(0.5~2).

[0020] Furthermore, the volume ratio of water to organic solvent is 1:(0.6~1.2).

[0021] More preferably, the volume ratio of water to organic solvent is 1:(0.8~1.2).

[0022] Most preferably, the volume ratio of water to organic solvent is 1:(1~1.2).

[0023] Preferably, the organic solvent is methanol.

[0024] Preferably, the temperature of the reduction reaction is 30~50℃.

[0025] Furthermore, the reduction reaction is carried out at a temperature of 35~50℃.

[0026] More preferably, the temperature of the reduction reaction is 35~40°C.

[0027] Preferably, the reduction reaction takes 3 to 6 hours.

[0028] Furthermore, the reduction reaction takes 4 hours.

[0029] Preferably, the reduction reaction is monitored for progress by thin-layer chromatography (TLC).

[0030] Preferably, the reduction reaction further includes post-processing.

[0031] Furthermore, the post-processing includes cooling, filtration, extraction, concentration, removal of impurities with organic solvents, filtration, and drying.

[0032] Preferably, the organic solvent used in the post-processing is any one of methyl tert-butyl ether, cyclohexane, and n-hexane.

[0033] More preferably, the organic solvent is methyl tert-butyl ether.

[0034] Furthermore, the conditions for removing impurities by adding organic solvent are: controlling the temperature at 20~30℃ and stirring for 20~40 min (preferably 30 min).

[0035] Preferably, the cooling is to cool the reaction product to room temperature.

[0036] Preferably, the extraction is performed by extracting the reaction product using dichloromethane.

[0037] Furthermore, the extraction is performed multiple times, preferably 1 to 3 times, and more preferably 2 times.

[0038] Preferably, the concentration is carried out by vacuum concentration to dryness.

[0039] Furthermore, the drying process is vacuum drying.

[0040] Furthermore, the drying conditions are: drying at 45~60 ℃ (preferably 50 ℃) for 3~5 h (preferably 4 h).

[0041] Specifically, the post-processing includes the following steps: cooling the product after complete reaction to room temperature and filtering to obtain a filtrate; extracting the obtained filtrate with dichloromethane, repeating this operation, combining the organic layers obtained from the two extractions, and concentrating under reduced pressure to dryness; then adding an organic solvent (preferably methyl tert-butyl ether) to remove impurities, filtering and drying to obtain the compound shown in Formula I.

[0042] Furthermore, the compound of formula II is obtained commercially.

[0043] The present invention has the following beneficial effects: This invention uses 2,3,4,5-tetrahydro-7,8-dinitro-3-(trifluoroacetyl)-1,5-methylene-1H-3-benzozaza as a raw material, and prepares 2,3,4,5-tetrahydro-7,8-diamino-3-(trifluoroacetyl)-1,5-methylene-1H-3-benzozaza by reduction with dithionite or its salt. This method does not require the use of hydrogen pressurization and avoids the use of heavy metal palladium. The reaction conditions are mild, the process is safe, and the cost is low. The target product has a high yield (>75%) and excellent purity (>97%), which is beneficial to the industrial production of varenicline tartrate. Attached Figure Description

[0044] Figure 1 The image shows the high-performance liquid chromatogram of the product obtained in Example 1. Detailed Implementation

[0045] The present invention will be further described below with reference to the accompanying drawings and specific embodiments, but the embodiments do not limit the present invention in any way. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in this technical field.

[0046] Unless otherwise specified, all reagents and materials used in the following examples are commercially available.

[0047] Source of compound II – (2,3,4,5-tetrahydro-7,8-dinitro-3-(trifluoroacetyl)-1,5-methylene-1H-3-benzodiazepine): Shanghai Haoyuan.

[0048] Source of reduced iron powder: Hengxing Reagent, product number 20200901.

[0049] Example 1: Preparation of 2,3,4,5-tetrahydro-7,8-diamino-3-(trifluoroacetyl)-1,5-methylene-1H-3-benzodiazepine The reaction pathway for 2,3,4,5-tetrahydro-7,8-diamino-3-(trifluoroacetyl)-1,5-methylene-1H-3-benzozazane is as follows: ; Specifically, the steps include the following: Compound II (1 eq, 20.00 g), water (200 mL), and methanol (200 mL) were added sequentially to a reaction flask and stirred for 5 min. Sodium dithionite (8 eq, 91.70 g) was then added. The reaction mixture was heated to 40 °C and maintained at this temperature for 4 h. The reaction progress was monitored by TLC. After the reaction was complete, the reaction mixture was cooled to room temperature and filtered. The filtrate was extracted with dichloromethane (160 mL), and this process was repeated. The organic layers obtained from the two extractions were combined and concentrated to dryness under reduced pressure. Methyl tert-butyl ether (40 mL) was then added to remove impurities. The temperature was controlled at 25 ± 5 °C, and the mixture was stirred for 30 min. The mixture was then filtered, and the filter cake was dried (at 50 °C for 4 h in a vacuum drying oven) to obtain the target product shown in Formula I. The yield was 15.05 g, representing 91.1%. The purity was 99.64% as determined by high-performance liquid chromatography (HPLC). The HPLC chromatogram of the product obtained in Example 1 is shown below. Figure 1 .

[0050] Example 2 Preparation of 2,3,4,5-tetrahydro-7,8-diamino-3-(trifluoroacetyl)-1,5-methylene-1H-3-benzodiazepine Compared with Example 1, the only difference is that the reaction temperature is changed from 40°C to 35°C, while the other steps and parameters are the same as in Example 1.

[0051] The results showed that the weight of the target product shown in Formula I was 14.61 g, the yield was 87.9%, and the purity was 99.67% as determined by high performance liquid chromatography.

[0052] Example 3 Preparation of 2,3,4,5-tetrahydro-7,8-diamino-3-(trifluoroacetyl)-1,5-methylene-1H-3-benzodiazepine Compared with Example 1, the only difference is that the reaction temperature is changed from 40°C to 45°C, while the other steps and parameters are the same as in Example 1.

[0053] The results showed that the weight of the target product shown in Formula I was 14.12 g, the yield was 84.9%, and the purity was 99.32% as determined by high performance liquid chromatography.

[0054] Example 4 Preparation of 2,3,4,5-tetrahydro-7,8-diamino-3-(trifluoroacetyl)-1,5-methylene-1H-3-benzodiazepine Compared with Example 1, the only difference is that the reaction temperature is changed from 40°C to 50°C, while the other steps and parameters are the same as in Example 1.

[0055] The results showed that the weight of the target product shown in Formula I was 14.16 g, the yield was 85.2%, and the purity was 99.16% as determined by high performance liquid chromatography.

[0056] Example 5 Preparation of 2,3,4,5-tetrahydro-7,8-diamino-3-(trifluoroacetyl)-1,5-methylene-1H-3-benzodiazepine Compared with Example 1, the only difference is that the amount of sodium dithionite added is 6 eq, and the other steps and parameters are the same as in Example 1.

[0057] The results showed that the weight of the target product shown in Formula I was 13.65 g, the yield was 82.1%, and the purity was 98.63% as determined by high performance liquid chromatography.

[0058] Example 6 Preparation of 2,3,4,5-tetrahydro-7,8-diamino-3-(trifluoroacetyl)-1,5-methylene-1H-3-benzodiazepine Compared with Example 1, the only difference is that the amount of sodium dithionite added is 10 eq, and the other steps and parameters are the same as in Example 1.

[0059] The results showed that the weight of the target product shown in Formula I was 15.23 g, the yield was 91.6%, and the purity was 99.59% as determined by high performance liquid chromatography.

[0060] Example 7 Preparation of 2,3,4,5-tetrahydro-7,8-diamino-3-(trifluoroacetyl)-1,5-methylene-1H-3-benzodiazepine Compared with Example 1, the only difference is that the amount of sodium dithionite added is 12 eq, and the other steps and parameters are the same as in Example 1.

[0061] The results showed that the weight of the target product shown in Formula I was 15.18 g, the yield was 91.3%, and the purity was 99.55% as determined by high performance liquid chromatography.

[0062] Example 8 Preparation of 2,3,4,5-tetrahydro-7,8-diamino-3-(trifluoroacetyl)-1,5-methylene-1H-3-benzodiazepine Compared with Example 1, the only difference is that methanol is replaced with an equal volume of ethanol, while the other steps and parameters are the same as in Example 1.

[0063] The results showed that the weight of the target product shown in Formula I was 12.49 g, the yield was 75.1%, and the purity was 97.61% as determined by high performance liquid chromatography.

[0064] Example 9 Preparation of 2,3,4,5-tetrahydro-7,8-diamino-3-(trifluoroacetyl)-1,5-methylene-1H-3-benzodiazepine Compared with Example 1, the only difference is that the amount of methanol added is 120 mL, that is, the volume-to-mass ratio of methanol to compound II is 6 v / w (mL / g). The other steps and parameters are the same as in Example 1.

[0065] The results showed that the weight of the target product shown in Formula I was 13.52 g, the yield was 81.3%, and the purity was 99.34% as determined by high performance liquid chromatography.

[0066] Example 10 Preparation of 2,3,4,5-tetrahydro-7,8-diamino-3-(trifluoroacetyl)-1,5-methylene-1H-3-benzodiazepine Compared with Example 1, the only difference is that the amount of methanol added is 160 mL, that is, the volume-to-mass ratio of methanol to compound II is 8 v / w (mL / g). The other steps and parameters are the same as in Example 1.

[0067] The results showed that the weight of the target product shown in Formula I was 14.90 g, the yield was 89.6%, and the purity was 99.60% as determined by high performance liquid chromatography.

[0068] Example 11 Preparation of 2,3,4,5-tetrahydro-7,8-diamino-3-(trifluoroacetyl)-1,5-methylene-1H-3-benzodiazepine Compared with Example 1, the only difference is that the amount of methanol added is 240 mL, that is, the volume-to-mass ratio of methanol to compound II is 12 v / w (mL / g). The other steps and parameters are the same as in Example 1.

[0069] The results showed that the weight of the target product shown in Formula I was 15.23 g, the yield was 91.6%, and the purity was 99.50% as determined by high performance liquid chromatography.

[0070] Preparation of Comparative Example 12,3,4,5-Tetrahydro-7,8-diamino-3-(trifluoroacetyl)-1,5-methylene-1H-3-benzozaza Compared with Example 1, the only difference is that methanol is replaced with an equal volume of isopropanol, while the other steps and parameters are the same as in Example 1.

[0071] The results showed that even after reacting for 24 hours, the target product could not be obtained by replacing methanol with isopropanol.

[0072] Comparative Example 2: Preparation of 2,3,4,5-tetrahydro-7,8-diamino-3-(trifluoroacetyl)-1,5-methylene-1H-3-benzodiazepine Compared to Example 1, sodium dithionite was replaced with a palladium on carbon / ammonium formate system for the reduction reaction, as follows: Preparation of ammonium formate solution: Dissolve ammonium formate (29.23 g) in water (120 mL) to obtain the solution.

[0073] Methanol (240 mL) was added to the reaction flask. Under nitrogen protection, Pd / C (3.00 g), containing 10% palladium on carbon, and compound II (20.00 g) were added sequentially. The mixture was stirred for 8 min, and ammonium formate solution was added dropwise. After the addition was complete, the mixture was stirred at 35 °C for 30 min. The reaction progress was monitored by TLC. After the reaction was complete, dichloromethane (100 mL) was added to the reaction solution, filtered through diatomaceous earth, and water (200 mL) was added to the filtrate. The mixture was stirred and allowed to stand for separation. The aqueous phase was extracted with dichloromethane (60 mL), and this operation was repeated. The organic phases obtained from the two extractions were combined, dried with anhydrous sodium sulfate (20.00 g), filtered, and the filtrate was concentrated to dryness under reduced pressure. The yield was 14.93 g, with a yield of 90.3%. The purity was 99.22% as determined by high performance liquid chromatography.

[0074] Preparation of Comparative Example 3: 2,3,4,5-Tetrahydro-7,8-diamino-3-(trifluoroacetyl)-1,5-methylene-1H-3-benzozazane Compared to Example 1, the sodium dithionite was replaced with an iron / acetic acid system for the reduction reaction, as detailed below: Acetic acid, compound II (20.00 g), and reduced iron powder (38.83 g) were added to the reaction flask. The mixture was heated to 80 °C and kept at this temperature for 6 h. Water (200 mL) was then added to the reaction solution, and the mixture was filtered. The filtrate was extracted with ethyl acetate (80 mL). This process was repeated twice. The organic phases obtained from the three extractions were combined, dried with anhydrous sodium sulfate (20.00 g), and filtered. The filtrate was concentrated to dryness under reduced pressure, and 10.91 g was obtained. The yield was 66.0%, and the purity was 20.83% as determined by high performance liquid chromatography.

[0075] Preparation of Comparative Example 4: 2,3,4,5-Tetrahydro-7,8-diamino-3-(trifluoroacetyl)-1,5-methylene-1H-3-benzodiazepine Compared to Example 1, sodium dithionite was replaced with sodium borohydride for the reduction reaction, as detailed below: Compound II (1 eq, 20.00 g) was dissolved in methanol (300 mL), cooled to 0 °C, and sodium borohydride (5.48 g, 2.5 eq) was slowly added. The mixture was then heated to 25 °C and stirred for 30 min. The solution was filtered, and the filtrate was concentrated to dryness under reduced pressure. Water (200 mL) was added to dissolve the solution, and the mixture was extracted with dichloromethane (80 mL) three times. The organic phases obtained from the three extractions were combined, dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated to dryness under reduced pressure, yielding 14.66 g, with a yield of 88.7%. The purity was determined to be 8.71% by high-performance liquid chromatography (HPLC).

[0076] Results Analysis (1) Effect of different reaction temperatures on the reaction results The experimental results of Examples 1 to 4 are summarized in Table 1.

[0077] Table 1 Effect of different reaction temperatures on the reaction

[0078] As shown in Table 1, the reduction reaction at a temperature of 35–50 °C yielded a high target product yield (>84%) and excellent purity (>99%). When the reaction temperature increased from 35 °C to 40 °C, the yield increased from 87.9% to 91.1%, and the purity reached 99.64%. When the temperature was further increased to 50 °C, the yield was only slightly higher than that at 45 °C, indicating that there was no monotonic correlation between the reaction temperature and the yield.

[0079] (2) Effect of different amounts of reducing agent added on the reaction results The experimental results of Examples 1, 5-7 are summarized in Table 2.

[0080] Table 2 Effect of different amounts of sodium dithionite on the reaction

[0081] As shown in Table 2, when the amount of sodium dithionite added is 6~12 eq, the yield of the target product is high (>82%) and the purity is excellent (>98%); especially when the amount of sodium dithionite added is 8~12 eq, the reaction yield reaches more than 90% and the purity also exceeds 99%.

[0082] (3) Effect of different reaction solvents on reaction results The experimental results of Examples 1, 8, and Comparative Example 1 are summarized in Table 3.

[0083] Table 3. Effects of different reaction solvents on the reaction

[0084] As shown in Table 3, when methanol or a combination of ethanol and water is used as the reaction solvent, the yield of the target product is high (>75%) and the purity is excellent (>97%). In particular, when methanol and water are used as the reaction solvent, the yield reaches 91.1% and the purity reaches 99.64%. However, when isopropanol and water are used as the reaction solvent, the target reaction product cannot be obtained even after 24 hours of reaction. This indicates that methanol or a combination of ethanol and water can effectively promote the reaction when used as the reaction solvent.

[0085] (4) Effect of different volume-to-mass ratios of methanol and the compound shown in II on the reaction results The experimental results of Examples 1, 9-11 are summarized in Table 4.

[0086] Table 4 shows the effect of different volume-to-mass ratios of methanol and the compound shown in II on the reaction.

[0087] Note: The v / w (mL / g) refers to the volume-to-mass ratio of methanol to the compound shown in Formula II.

[0088] As shown in Table 4, when the volume mass ratio of methanol to the compound shown in Formula II is 6~12 v / w (mL / g), the yield of the target product is high (>80%) and the purity is excellent (>99%). In particular, when the volume mass ratio of methanol to the compound shown in Formula II is 8~12 v / w (mL / g), the yield reaches more than 90% and the purity also exceeds 99%.

[0089] (5) Effect of different reduction systems on reaction results The experimental results of Example 1 and Comparative Examples 2-4 are summarized in Table 5.

[0090] Table 5. Effects of different reduction systems on the reaction

[0091] As shown in Table 5, when Comparative Example 3 used the iron / acetic acid reaction system, the yield of the reaction product was significantly low (<70%) and the purity was poor (<21%). Further purification was required before subsequent reactions, making the operation complex and unfavorable for the industrial production of varenicline tartrate. While Comparative Example 4 used sodium borohydride for the reduction reaction, the product yield was relatively high, but the product purity was extremely low (<10%). Similarly, further purification was required before subsequent reactions, making the operation complex and unfavorable for the industrial production of varenicline tartrate. Although Comparative Example 2 used the palladium on carbon / ammonium formate system for the reduction reaction, the product yield was high and the purity was excellent. However, its reliance on the precious metal palladium, its high cost, and the environmental pollution caused by subsequent heavy metal treatment and emissions limit the application of this system in large-scale industrial production, thus hindering the production of varenicline tartrate. The present invention uses sodium dithionite for the reduction reaction, which avoids the use of the precious metal palladium. The yield and purity of the target product are comparable to those using palladium-based catalysts. Moreover, sodium dithionite is inexpensive and readily available, making it more suitable for the large-scale industrial production of varenicline tartrate.

[0092] In summary, this invention uses 2,3,4,5-tetrahydro-7,8-dinitro-3-(trifluoroacetyl)-1,5-methylene-1H-3-benzozaza as a raw material, and prepares 2,3,4,5-tetrahydro-7,8-diamino-3-(trifluoroacetyl)-1,5-methylene-1H-3-benzozaza by reduction with dithionite or its salt. This method eliminates the need for hydrogen pressurization and avoids the use of the heavy metal palladium. The reaction conditions are mild, the process is safe, and the cost is low. The target product has a high yield (>75%) and excellent purity (>97%), which is beneficial for the industrial production of varenicline tartrate.

[0093] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. A method for preparing a varenicline tartrate intermediate, characterized in that, Includes the following steps: The compound shown in Formula II is reduced with dithionite or its salt in the presence of a solvent to obtain the varenicline tartrate intermediate: ； The solvent is a combination of water and an organic solvent, wherein the organic solvent is selected from methanol and / or ethanol.

2. The method as described in claim 1, characterized in that, The molar ratio of the compound shown in Formula II to dithionite or its salt is 1:(5~15).

3. The method as described in claim 1, characterized in that, The dithionite or its salts include one of sodium dithionite, potassium dithionite, zinc dithionite, and calcium dithionite.

4. The method as described in claim 1, characterized in that, The salt in the dithionite or its salt is sodium dithionite.

5. The method as described in claim 1, characterized in that, The volume-to-mass ratio of the organic solvent to the compound shown in Formula II is (5~15) mL:1 g.

6. The method as described in claim 1, characterized in that, The volume ratio of water to organic solvent is 1:(0.5~2).

7. The method as described in claim 1, characterized in that, The reduction reaction is carried out at a temperature of 30~50℃.

8. The method as described in claim 1, characterized in that, The reduction reaction takes 3 to 6 hours.

9. The method as described in claim 1, characterized in that, The reduction reaction also includes post-processing.

10. The method as described in claim 9, characterized in that, The post-processing includes cooling, filtration, extraction, concentration, removal of impurities with organic solvents, filtration, and drying.

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