Preparation method of 2, 5-bis (aminomethyl) tetrahydrofuran

Abstract

The invention relates to a preparation method of a compound IV, which comprises the following reaction: # imgabs0 # comprises the following steps: step (1): reacting a compound I in benzylamine to obtain a compound II; (2) carrying out reduction reaction on the compound II in the presence of a reducing agent, and reacting with a hydrochloric acid reagent to obtain a compound III; and (3) carrying out reaction on the compound III in the presence of a metal catalyst and a hydrogen source to obtain a compound IV. According to the process route disclosed by the invention, dihydrochloride is selected in the synthesis process, so that the amino activity can be effectively inhibited, intermolecular polymerization reaction caused by amino is avoided, the yield of a reaction system is improved, the property of an intermediate is stable, the reproducibility is good, the preparation method is simple and convenient to operate, the yield is high, the product quality is good, and industrial production is easy to realize.

Description

Technical Field

[0001] The invention relates to 2,5-bis(aminomethyl)tetrahydrofuran, which belongs to the field of preparing energy chemicals through biomass conversion. Background Art

[0002] Diamines can be used to prepare polyamides and polyurethanes. Polyamides and polyurethanes have always been the preferred materials in engineering plastics. If a method for efficiently converting diamines from biomass can be developed, it will be possible to achieve biomass-based production of polyamides and polyurethanes. 2,5-Bis(aminomethyl)tetrahydrofuran (BAMTHF) is an important biomass-based monomer that can be used as a monomer for bio-based polyamides or polyurethanes. The structure is shown below:

[0003]

[0004] Patent CN105377971B discloses that 2,5-bis(aminomethyl)tetrahydrofuran is prepared from 5-hydroxymethylfurfural as the starting material through reduction, esterification, substitution, and reduction; the total yield of the four steps is 71%, but it needs to undergo two hydrogenation reductions, and requires the use of highly toxic reagents such as methanesulfonyl chloride and explosive and highly toxic sodium azide. The metal catalyst is expensive and dangerous, and this method is not conducive to industrial scale-up. The preparation method is as follows:

[0005]

[0006] Patent CN108129425B discloses that furan-2,5-dicarboxaldehyde dioxime is used as raw material, and the conversion rate can reach more than 90%, but this method requires a catalytic hydrogenation temperature of 130°C, and the reaction conditions are relatively harsh, which is not conducive to industrial scale-up. The preparation method is as follows:

[0007]

[0008] Patent CN117263886A discloses that 2,5-tetrahydrofuran dimethanol is used as the starting material, and 2,5-bis(aminomethyl)tetrahydrofuran is prepared through esterification, substitution, and hydrolysis. The second step of substitution in this method needs to react at 150°C, which is a high temperature and is not conducive to industrial scale-up. The preparation method is as follows:

[0009]

[0010] Patent CN110325520A discloses 2,5-tetrahydrofuran dimethanol as the starting material and discloses three routes. The preparation method is as follows:

[0011] Route 1:

[0012]

[0013] Route 2:

[0014]

[0015] Route 3:

[0016]

[0017] Route 1 prepares 2,5-bis(aminomethyl)tetrahydrofuran through three steps. This method requires two hydrogenation reactions and uses hydrazine hydrate, an explosive reagent. The metal catalyst is relatively expensive, which is not conducive to industrial scale-up. Route 2 uses dioxime as a raw material and uses 5% Pd / C for catalytic hydrogenation to obtain 2,5-bis(aminomethyl)tetrahydrofuran, producing 5% of polymerization by-products. Route 3 reports the use of dioxime as a raw material, and obtains 2,5-bis(aminomethyl)tetrahydrofuran through Raney nickel catalytic hydrogenation, producing about 12% of polymerization by-products. Summary of the invention

[0018] In view of the defects of low yield or harsh conditions in the prior art, the present invention provides a method for preparing 2,5-bis(aminomethyl)tetrahydrofuran, which is simple, efficient, and has a high yield, greatly reduces the cost, and is conducive to large-scale commercial production.

[0019] In order to achieve the above technical objectives, the present invention adopts the following technical solutions:

[0020] The first aspect of the present invention provides a method for preparing compound IV, and the reaction formula is as follows:

[0021]

[0022] The steps include:

[0023] Step (1): Compound I reacts with benzylamine to obtain compound II;

[0024] Step (2): Compound II is subjected to a reduction reaction in the presence of a reducing agent, and reacted with a hydrochloric acid reagent to obtain Compound III;

[0025] Step (3): Compound III is reacted in the presence of a metal catalyst and a hydrogen source to obtain compound IV.

[0026] As a further improvement of the present invention, including but not limited to, the reaction in step (1) comprises: compound I reacts with benzylamine in an organic solvent to obtain compound II;

[0027] As a further improvement of the present invention, the molar ratio of compound I to benzylamine in step (1) is 1:(2.05-3.5), preferably 1:(2.08-2.5);

[0028] As a further improvement of the present invention, including but not limited to, the organic solvent in the step (1) is selected from one or a combination of ether solvents, halogenated alkane solvents, ketone solvents, aromatic hydrocarbon solvents, nitrile solvents, ester solvents, alcohol solvents, sulfone solvents and amide solvents, preferably an alcohol solvent; the ether solvent is selected from one or a combination of tetrahydrofuran, 2-methyltetrahydrofuran or dioxane; the halogenated alkane solvent is selected from one or a combination of dichloromethane, dichloroethane or chloroform; the ketone solvent is preferably acetone; the aromatic hydrocarbon solvent is selected from one or a combination of toluene or xylene; the nitrile solvent is preferably acetonitrile; the ester solvent is selected from one or a combination of ethyl acetate, ethyl formate or isopropyl acetate; the alcohol solvent is selected from one or a combination of methanol, ethanol or isopropanol; the sulfone solvent is preferably dimethyl sulfoxide; the amide solvent is selected from one or a combination of N,N-dimethylformamide or N,N-dimethylacetamide;

[0029] As a further improvement of the present invention, including but not limited to, the organic solvent in step (1) is selected from one or a combination of toluene, xylene, tetrahydrofuran, 2-methyltetrahydrofuran, dioxane, methanol, ethanol, propanol, N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, dichloromethane, and dimethyl sulfoxide, preferably methanol;

[0030] As a further improvement of the present invention, including but not limited to, the volume amount of the organic solvent in step (1) mL is 5 to 20 times the mass amount of compound I g, preferably 6 to 10 times;

[0031] As a further improvement of the present invention, including but not limited to, the reaction temperature of step (1) is 10 to 30°C;

[0032] As a further improvement of the present invention, including but not limited to, the reaction time of step (1) is 0.5 to 5 hours, preferably 0.5 to 2 hours.

[0033] As a further improvement of the present invention, including but not limited to, the reaction in step (2) comprises: compound II is subjected to a reduction reaction with a reducing agent in an organic solvent, and then reacted with a hydrochloric acid reagent to obtain compound III;

[0034] As a further improvement of the present invention, the reduction reaction time in step (2) is 0.5 to 8 hours, preferably 1.5 to 4.5 hours;

[0035] As a further improvement of the present invention, in the reaction of step (2), the reaction time of the further reaction with the hydrochloric acid reagent is 0.5 to 3 hours, preferably 0.5 to 2 hours.

[0036] As a further improvement of the present invention, including but not limited to, the hydrochloric acid reagent in step (2) is selected from one or a combination of concentrated hydrochloric acid, dilute hydrochloric acid, hydrochloric acid / ethyl acetate solution, hydrochloric acid / dioxane solution, hydrochloric acid / ethanol solution, and hydrochloric acid / methanol solution, preferably hydrochloric acid / ethyl acetate solution;

[0037] As a further improvement of the present invention, including but not limited to, the molar ratio of compound II to hydrochloric acid reagent in step (2) is 1:(2-5), preferably 1:(2.01-3);

[0038] As a further improvement of the present invention, including but not limited to, the reducing agent in step (2) is selected from one or a combination of sodium borohydride, potassium borohydride, lithium borohydride, zinc borohydride, and aluminum borohydride, preferably sodium borohydride;

[0039] As a further improvement of the present invention, including but not limited to, the molar ratio of compound II to the reducing agent in step (2) is 1:(2-5), preferably 1:(2.01-3);

[0040] As a further improvement of the present invention, including but not limited to, the organic solvent in step (2) is selected from one or a combination of methanol, ethanol, propanol, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, tetrahydrofuran, 2-methyltetrahydrofuran, dioxane, dichloromethane, dichloroethane, chloroform, acetone, acetonitrile, ethyl acetate, ethyl formate, and isopropyl acetate, preferably ethanol or ethyl acetate;

[0041] As a further improvement of the present invention, including but not limited to, the volume amount of the organic solvent in step (2) mL is 3 to 15 times the mass amount of compound II g, preferably 5 to 12 times;

[0042] As a further improvement of the present invention, including but not limited to, the reaction temperature of step (2) is 10 to 45°C, preferably 15 to 35°C.

[0043] As a further improvement of the present invention, including but not limited to, the reaction of step (2) comprises: after the reduction reaction, quenching, filtering, and concentrating; adding ethyl acetate to extract and separate the liquid, adding hydrochloric acid / ethyl acetate solution dropwise to the organic phase and stirring to form a salt; filtering, rinsing the filter cake with ethyl acetate, and filtering to obtain a solid compound III.

[0044] As further improvements of the present invention, including but not limited to, the step (2) of the present invention cleverly uses a one-pot method, first reducing and then directly reacting to form a salt in the organic phase, thereby reducing manpower and material resources and saving costs.

[0045] As a further improvement of the present invention, including but not limited to, the reaction in step (3) comprises: compound III reacts in an organic solvent in the presence of a metal catalyst and a hydrogen source to obtain compound IV;

[0046] As a further improvement of the present invention, including but not limited to, the hydrogen pressure of the reaction in step (3) is selected from 0.5 to 10 MPa, preferably 4 to 6 MPa;

[0047] As a further improvement of the present invention, including but not limited to, the metal catalyst in step (3) is selected from one or a combination of palladium carbon (Pd / C), palladium hydroxide (Pd(OH)2), platinum carbon (Pt / C), rhodium-alumina (Rh / Al2O3), preferably palladium carbon (Pd / C);

[0048] As a further improvement of the present invention, including but not limited to, the metal catalyst in step (3) is selected from Pd / C, preferably 5% Pd / C or 10% Pd / C, and further preferably 10% Pd / C;

[0049] As a further improvement of the present invention, including but not limited to, the mass g ratio of the compound III to the metal catalyst in step (3) is 1:(0.01-0.1), preferably 1:(0.03-0.06); for example 1:0.05;

[0050] As a further improvement of the present invention, including but not limited to, the organic solvent in step (3) is selected from one or a combination of methanol, propanol, N,N-dimethylformamide, N,N-dimethylacetamide, tetrahydrofuran, dioxane, dichloromethane, dichloroethane, chloroform, acetone, toluene, acetonitrile, and ethyl acetate, preferably methanol;

[0051] As a further improvement of the present invention, including but not limited to, the volume amount of the organic solvent in step (3) mL is 5 to 20 times the mass amount of compound III g, preferably 6 to 12 times, for example 10 times;

[0052] As a further improvement of the present invention, including but not limited to, the reaction temperature of step (3) is 35 to 100° C., preferably 55 to 85° C.;

[0053] As a further improvement of the present invention, including but not limited to, the reaction time of step (3) is 3 to 20 hours, preferably 5 to 12 hours;

[0054] As a further improvement of the present invention, including but not limited to, the post-reaction treatment method for the preparation of compound IV in step (3) includes filtering after the reaction is completed; or selectively using an organic solvent for distillation, preferably using ethanol for distillation 1 to 6 times or 1 to 4 times, for example, 1 time, 2 times, 3 times, 4 times, 5 times or 6 times; recrystallizing with ethanol, and drying with air at 25 to 50° C. to obtain solid compound IV.

[0055] As a further improvement of the present invention, including but not limited to, the present invention uses the free base of compound III for reaction, and it is found that the reaction is more complicated and more by-products appear. However, when the dihydrochloride is used for reaction, the reaction yield can reach 85%, and the use of the dihydrochloride can effectively inhibit the activity of the amine group and avoid the intermolecular polymerization reaction caused by the amine group. The prior art CN110325520A uses Raney nickel to prepare 2,5-bis(aminomethyl)tetrahydrofuran, and about 12% of polymerization by-products will appear. The process route of the present invention can solve the problem of intermolecular polymerization by-products.

[0056] The second aspect of the present invention provides a method for preparing compound IV, and the reaction formula is as follows:

[0057]

[0058] The preparation methods of steps (2) to (3) in this scheme are as described above in the first aspect of the present invention.

[0059] The steps include:

[0060] Step (2): Compound II is subjected to a reduction reaction in the presence of a reducing agent, and reacted with a hydrochloric acid reagent to obtain Compound III;

[0061] Step (3): Compound III is reacted in the presence of a metal catalyst and a hydrogen source to obtain compound IV.

[0062] The third aspect of the present invention provides a compound III, the structure of which is as follows:

[0063]

[0064] The fourth aspect of the present invention also provides a method for preparing compound V, comprising preparing compound IV by the preparation method of compound IV of the first or second aspect of the present invention, and further preparing compound V by compound IV; the reaction formula is shown below:

[0065]

[0066] Beneficial technical effects of the present invention:

[0067] 1) The present invention uses 2,5-diformylfuran as a starting material, and prepares compound IV through substitution, reduction, and catalytic hydrogenation, thereby avoiding the use of toxic reagents, explosive reagents, and high temperature conditions in the prior art, and has simple operation, high yield, and simple post-treatment. The product can be obtained only by a pulping purification method, and is easy to realize industrial production;

[0068] 2) The inventors repeated the reduction conditions of the prior art CN110325520A and found that the solubility of dioxime was poor, and the reduction reaction was difficult to carry out, resulting in no product. The present invention improved the solubility of the intermediate by replacing hydroxylamine with benzylamine, so that the subsequent reduction can proceed smoothly;

[0069] 3) The inventors selected the free base of compound III for the reaction and found that the reaction was more complicated and more by-products appeared. However, when the dihydrochloride was used for the reaction, the reaction yield could reach 85% and the purity could reach 98%. The dihydrochloride could effectively inhibit the activity of the amine group and avoid the intermolecular polymerization reaction caused by the amine group. The prior art CN110325520A uses Raney nickel to prepare 2,5-bis(aminomethyl)tetrahydrofuran, which will produce about 12% of polymerization by-products. The process route of the present invention can solve the problem of intermolecular polymerization by-products, and the intermediates are stable in nature and have good reproducibility. The preparation method is simple to operate, the product quality is good, and it is easy to realize industrial production.

[0070] 4) The process route of the present invention is short, the conditions are mild, the operation is simple, the yield is high, the post-treatment is simple, and the product can be obtained only by a pulping purification method, which reduces "three wastes" and is suitable for industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0071] Figure 1 This is the HPLC spectrum of the product obtained in Example 2.1 of the present invention;

[0072] Figure 2 The product obtained in Example 2.1 of the present invention 1 H-NMR spectrum;

[0073] Figure 3 The product obtained in Example 4.1 of the present invention 1 H-NMR spectrum;

[0074] Figure 4 The GC spectrum of the product obtained in Comparative Example 3 of the present invention is shown in FIG. DETAILED DESCRIPTION

[0075] The preparation method of the present invention will be described in further detail below in conjunction with specific examples. It should be understood that the following examples are only exemplary illustrations and explanations of the present invention and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are included in the scope that the present invention is intended to protect.

[0076] Unless otherwise specified, the experimental methods used in the following examples are all conventional methods; the reagents, materials, etc. used in the following examples, unless otherwise specified, can be obtained from commercial channels.

[0077] Example 1.1:

[0078]

[0079] 2,5-diformylfuran (185 g, 1.49 mol) and 1.2 L of methanol were added to a 2 L three-necked flask and stirred. Benzylamine (335.5 g, 3.13 mol) was added dropwise at room temperature and stirred for 1 h. The reaction progress was tracked by HPLC. A large amount of solid was generated during the reaction. After the reaction was completed, the filter cake was rinsed twice with 185 mL of methanol. The wet product was dried at 35-45 ° C with forced air for 16 h to obtain yellow solid compound II (389 g, yield 86.4%).

[0080] Examples 1.2 to 1.5 Referring to the method of Example 1.1, the amount of benzylamine was changed to prepare the product compound II, as shown in Table 1 below.

[0081] Table 1

[0082]

[0083] Examples 1.5 to 1.8: Referring to the method of Example 1.1, the volume of solvent was changed to prepare Compound I, as shown in Table 2 below.

[0084] Table 2

[0085]

[0086] Through creative work, the inventors finally determined the appropriate equivalent of benzylamine and solvent and the volumetric dosage of the solvent. For example, it can be seen from Examples 1.1 to 1.4 in Table 1 that when the molar equivalent of compound I to benzylamine is 2.1 to 2.35, the yield is the best. When the molar equivalent is other than this, the raw material reaction is not complete and the product is difficult to purify in the reaction solution. For example, it can be seen from Examples 1.5 to 1.8 in Table 2 that when methanol is used as a solvent, the mass dosage of compound I g and the volume dosage of methanol mL are 7.5. The reaction effect is the best, and the content of the controlled product is 95%. When ethanol is used as a solvent, although the content of the controlled product can also reach 93%, the volume dosage of the solvent is about 1.5 times that of methanol. From the perspective of economic and environmental protection, methanol is selected as a solvent, and the molar equivalent of compound I to benzylamine is 2.1 to 2.35. When, the effect is best, it has the advantages of simple post-treatment, good reproducibility, and high conversion rate, and is suitable for industrial production.

[0087] Example 2.1:

[0088]

[0089] Add compound II (370g, 1.22mol) and 3.7L ethanol to a 5L three-necked flask, start stirring and cool to 15°C, add sodium borohydride (108.8g, 2.93mol) and stir for 2-4h. After the reaction of the raw materials is completed by HPLC monitoring, control the temperature below 30°C, first slowly drop 2.5L of 1mol / L dilute hydrochloric acid, then add 1.6L saturated sodium carbonate solution, filter, and concentrate. Subsequently, add 1.5L ethyl acetate to extract and separate the liquids, drop 629mL (4mol / L) HCl / EA solution to the organic phase and stir for 1h to form a salt. Filter, rinse the filter cake with ethyl acetate, and dry the wet product at 40-50°C with air for 10h to obtain a white solid compound III (418g, HPLC purity 98.1%, Rt=9.172min, yield 90%). The HPLC spectrum is shown as follows Figure 1 As shown, 1 H-NMR spectrum Figure 2 shown.

[0090] Example 3.1:

[0091]

[0092] Compound III (250 g, 0.66 mol) was added to a 5L three-necked flask, and 2.5L of methanol was stirred. 10% palladium carbon (12.5 g) catalyst was added and the temperature was raised to 60°C, followed by hydrogenation to 5 MPa, and the temperature was kept at 80°C for 6 hours. After the reaction was completed, the organic phase was filtered, concentrated under reduced pressure and evaporated with ethanol. It was then recrystallized from ethanol. The wet product was dried at 35-40°C with forced air for 12 hours to obtain an off-white solid compound IV (113.8 g, yield 85%, purity 98%).

[0093] Example 3.2 Referring to the operation method of Example 3.1, the solvent was changed to prepare the product compound IV, as shown in Table 3 below:

[0094] Table 3

[0095] Example Solvents Results and Discussion Example 3.1 Methanol After 6 hours of reaction, the raw material was completely converted, with a yield of 85%. Example 3.2 Ethanol Reaction time 12h, basically no reaction

[0096] The inventors have finally determined a suitable solvent through creative work. For example, it can be seen from Examples 3.1 to 3.2 in Table 3 that when ethanol is used as a solvent, even if the reaction time is extended, the raw materials will basically not react. Therefore, using methanol as a solvent has the best effect, with a yield of up to 85%. It also has the advantages of simple post-processing and good reproducibility, and is suitable for industrial production.

[0097] Example 4.1:

[0098]

[0099] Compound IV (100 g, 0.66 mol) and 500 mL of ethanol were added to a 3L three-necked flask and stirred. NaOH (39.9 g, dissolved in 40 mL of water) solution was added and then reacted at room temperature for 0.5 h. After the reaction was completed, the mixture was filtered and the filter cake was rinsed twice with ethanol and purified to obtain a colorless oily compound V (62.7 g, yield 98.3%). 1 H-NMR spectrum Figure 3 shown.

[0100] Comparative Example 1:

[0101]

[0102] Compound I (30 g) was placed in a 500 mL three-necked flask, 210 mL of ethanol was added, and 90 mL of water was used to dissolve hydroxylamine hydrochloride. The mixture was added dropwise to the system at a temperature of 25-35°C. After the addition was completed, stirring was continued for 20 min. TLC showed that the reaction was complete. The mixture was cooled to 20°C and filtered. The filter cake was rinsed with water twice. 81.4 g of a light yellow solid wet product was obtained, which was dried at 50°C for 18 h.

[0103] Comparative Example 2:

[0104]

[0105] Raney nickel (100 mg) was put into a reaction bottle, and dioxane (6 mL) and compound II-1 (500 mg) were added to replace the hydrogen. Under a pressure of 4 MPa, the temperature was raised to 120° C. and stirred for 3 h. No new spots were generated by TLC monitoring.

[0106] Comparative Examples 2.1 to 2.3 The products were prepared by referring to the operation method of Comparative Example 2, and changing the catalyst, solvent and pressure, as shown in Table 4 below.

[0107] Table 4

[0108]

[0109] Comparative Example 3:

[0110]

[0111] Compound III-2 (250 mg, 0.82 mmol) and 25 mL of methanol were added to a 100 mL three-necked flask and stirred. 10% palladium carbon (75 mg) catalyst was added and the temperature was raised to 60°C, followed by hydrogenation to 5 MPa and heat preservation at 80°C for 6 h. GC monitoring showed that the reaction was more complicated and the purity was lower. The GC spectrum is shown in Figure 4 shown.

Claims

1. A method for preparing compound IV, the reaction formula is as follows: The steps include: Step (1): Compound I reacts with benzylamine to obtain compound II; Step (2): Compound II is subjected to a reduction reaction in the presence of a reducing agent, and reacted with a hydrochloric acid reagent to obtain Compound III; Step (3): Compound III is reacted in the presence of a metal catalyst and a hydrogen source to obtain compound IV.

2. A method for preparing compound IV, the reaction formula is as follows: The steps include: Step (2): Compound II is subjected to a reduction reaction in the presence of a reducing agent, and reacted with a hydrochloric acid reagent to obtain Compound III; Step (3): Compound III is reacted in the presence of a metal catalyst and a hydrogen source to obtain compound IV.

3. The preparation method according to claim 1, characterized in that: Compound I reacts with benzylamine in an organic solvent to obtain compound II; the step (1) further satisfies one or more of the following conditions: And / or, preferably, the molar ratio of the compound I to benzylamine is 1:(2.05-3.5), preferably 1:(2.08-2.5); And / or, preferably, the organic solvent is selected from one or a combination of ether solvents, halogenated alkane solvents, ketone solvents, aromatic hydrocarbon solvents, nitrile solvents, ester solvents, alcohol solvents, sulfone solvents and amide solvents, preferably an alcohol solvent; the ether solvent is selected from one or a combination of tetrahydrofuran, 2-methyltetrahydrofuran or dioxane; the halogenated alkane solvent is selected from one or a combination of dichloromethane, dichloroethane or chloroform; the ketone solvent is preferably acetone; the aromatic hydrocarbon solvent is selected from one or a combination of toluene or xylene; the nitrile solvent is preferably acetonitrile; the ester solvent is selected from one or a combination of ethyl acetate, ethyl formate or isopropyl acetate; the alcohol solvent is selected from one or a combination of methanol, ethanol or isopropanol; the sulfone solvent is preferably dimethyl sulfoxide; the amide solvent is selected from one or a combination of N,N-dimethylformamide or N,N-dimethylacetamide; And / or, preferably, the organic solvent is selected from one or a combination of toluene, xylene, tetrahydrofuran, 2-methyltetrahydrofuran, dioxane, methanol, ethanol, propanol, N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, dichloromethane, and dimethyl sulfoxide, preferably methanol; And / or, preferably, the volume amount of the organic solvent mL is 5 to 20 times the mass amount of compound I g, preferably 6 to 10 times; And / or, preferably, the reaction temperature is 10 to 30°C; And / or, preferably, the reaction time is 0.5 to 5 h, preferably 0.5 to 2 h.

4. The preparation method according to claim 1 or 2, characterized in that: Compound II is subjected to a reduction reaction with a reducing agent in an organic solvent, and then reacted with a hydrochloric acid reagent to obtain compound III; the step (2) further satisfies one or more of the following conditions: And / or, preferably, the hydrochloric acid reagent is selected from one or a combination of concentrated hydrochloric acid, dilute hydrochloric acid, hydrochloric acid / ethyl acetate solution, hydrochloric acid / dioxane solution, hydrochloric acid / ethanol solution, and hydrochloric acid / methanol solution, preferably hydrochloric acid / ethyl acetate solution; And / or, preferably, the molar ratio of the compound II to the hydrochloric acid reagent is 1:(2-5), preferably 1:(2.01-3); And / or, preferably, the volume amount of the organic solvent in mL is 3 to 15 times, preferably 5 to 12 times, the mass amount of compound II in g; And / or, preferably, the organic solvent is selected from methanol, ethanol, propanol, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, tetrahydrofuran, 2-methyltetrahydrofuran, dioxane, dichloromethane, dichloroethane, chloroform, acetone, acetonitrile, ethyl acetate, ethyl formate, isopropyl acetate or a combination thereof, preferably ethanol or ethyl acetate; And / or, preferably, the molar ratio of the compound II to the reducing agent is 1:(2-5), preferably 1:(2.01-3); And / or, preferably, the reducing agent is selected from one or a combination of sodium borohydride, potassium borohydride, lithium borohydride, zinc borohydride, and aluminum borohydride, preferably sodium borohydride; And / or, preferably, the reaction temperature is 10-45°C, preferably 15-35°C.

5. The preparation method according to claim 1 or 2, characterized in that: The step (2) further satisfies one or more of the following conditions: And / or, preferably, the reduction reaction time is 0.5 to 8 h, preferably 1.5 to 4.5 h; And / or, preferably, the reaction time of the further reaction with the hydrochloric acid reagent is 0.5 to 3 hours, preferably 0.5 to 2 hours.

6. The preparation method according to claim 1 or 2, characterized in that: The reaction of step (2) comprises: after the reduction reaction, quenching, filtering, and concentrating; adding ethyl acetate to extract and separate the liquid, dripping hydrochloric acid / ethyl acetate solution into the organic phase and stirring to form salt; filtering, rinsing the filter cake with ethyl acetate, and filtering to obtain solid compound III.

7. The preparation method according to claim 1 or 2, characterized in that: Compound III is reacted in an organic solvent in the presence of a metal catalyst and a hydrogen source to obtain compound IV; the step (3) further satisfies one or more of the following conditions: And / or, preferably, the reaction hydrogen pressure is selected from 0.5 to 10 MPa, preferably 4 to 6 MPa; And / or, preferably, the metal catalyst is selected from one or a combination of Pd / C, Pd(OH)2, Pt / C, Rh / Al2O3, preferably Pd / C; And / or, preferably, the metal catalyst is selected from Pd / C, preferably 5% Pd / C or 10% Pd / C, further preferably 10% Pd / C; And / or, preferably, the mass ratio g of the compound III to the metal catalyst is 1:(0.01-0.1), preferably 1: (0.03～0.06)； And / or, preferably, the organic solvent is one or a combination of methanol, propanol, N,N-dimethylformamide, N,N-dimethylacetamide, tetrahydrofuran, dioxane, dichloromethane, dichloroethane, chloroform, acetone, toluene, acetonitrile, and ethyl acetate, preferably methanol; And / or, preferably, the volume dosage of the organic solvent mL is 5 to 20 times, preferably 6 to 12 times, the mass dosage g of compound III; And / or, preferably, the reaction temperature is 35 to 100°C, preferably 55 to 85°C; And / or, preferably, the reaction time is 3 to 20 hours, preferably 5 to 12 hours.

8. The preparation method according to claim 1 or 2, characterized in that: The post-reaction treatment method for preparing compound IV in step (3) includes filtering after the reaction; or selectively using an organic solvent for distillation, preferably using ethanol for distillation 1 to 6 times, recrystallizing with ethanol, and drying with air at 25 to 50° C. to obtain solid compound IV.

9. A compound III having the following structure:

10. A method for preparing compound V, comprising preparing compound IV by the preparation method according to any one of claims 1 to 8, and further reacting compound IV to prepare compound V, wherein the reaction formula is as follows:

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