A process for the preparation of (r)-1-(tetrahydrofuran-2-yl)ethylamine

Abstract

The application relates to the technical field of chiral organic compound synthesis, and particularly discloses a preparation method of (R)-1-(tetrahydrofuran-2-yl)ethylamine. The method uses cheap and readily available (R)-tetrahydrofuran-2-carboxylic acid as a starting material, and sequentially carries out methyl esterification, nucleophilic substitution, Grignard methylation, reductive amination, and salt precipitation-alkali dissociation purification steps under the catalysis of a tertiary amine sulfonic acid inner salt type polymeric ionic liquid resin, so as to obtain a target product with high optical purity. The application introduces a polymeric ionic liquid resin catalyst with a specific structure, inhibits racemization of an alpha-chiral center in an esterification process from the source, ensures complete retention of chiral configurations in each process step, fundamentally solves the problem of optical purity reduction caused by a traditional concentrated sulfuric acid catalysis process, can stably maintain the ee value of the target product at more than 99%, the product has high optical purity, and the method is easy to realize large-scale industrial production, so the method has remarkable industrial application value and economic benefits.

Description

Technical Field

[0001] This invention relates to the field of chiral organic compound synthesis technology, and in particular to a method for preparing (R)-1-(tetrahydrofuran-2-yl)ethylamine. Background Technology

[0002] (R)-1-(tetrahydrofuran-2-yl)ethylamine is an important chiral primary amine intermediate. Its molecular structure simultaneously contains a chiral center, a tetrahydrofuran heterocycle, and an amino functional group, exhibiting excellent reactivity and flexible structural modification capabilities. It is widely used in pharmaceuticals, pesticides, and new materials, playing an irreplaceable role as a key chiral building block, particularly in the synthesis of drugs for cardiovascular diseases and antitumor diseases. With the continued development of the chiral drug market, the demand for high-purity, low-cost (R)-1-(tetrahydrofuran-2-yl)ethylamine is increasing, making the development of efficient and green preparation methods a current research hotspot in this field.

[0003] Currently, the existing technologies for preparing (R)-1-(tetrahydrofuran-2-yl)ethylamine mainly fall into three categories: First, using chiral alcohols (such as (R)-1-(tetrahydrofuran-2-yl)ethanol) or chiral halides (such as (R)-2-(1-haloethyl)tetrahydrofuran) as starting materials, and preparing them through ammonolysis. However, the starting materials are expensive, and the ammonolysis reaction requires high pressure and high temperature conditions, making the reaction conditions harsh and requiring large equipment investments. Second, some technologies use racemic resolution to prepare (R)-1-(tetrahydrofuran-2-yl)ethylamine. This method requires expensive chiral resolving agents, which not only further increases production costs but also results in low resolution yields. Furthermore, the resolution process generates a large number of byproducts, leading to high levels of waste gas, wastewater, and solid waste, which does not meet the requirements of green chemical development. Third, some synthetic methods involve cumbersome steps, requiring intermediate products to undergo complex purification processes such as column chromatography for separation and purification. These methods are difficult to operate, have low production efficiency, and are difficult to scale up for industrial production.

[0004] Therefore, there is an urgent need to develop a new method for preparing (R)-1-(tetrahydrofuran-2-yl)ethylamine that uses readily available raw materials, has mild reaction conditions, simple steps, stable yield, and is cost-effective and efficient in purification. Summary of the Invention

[0005] To address the problems of high raw material costs, harsh reaction conditions, complex purification processes, and low yields in existing methods for preparing (R)-1-(tetrahydrofuran-2-yl)ethylamine, this invention provides a method for preparing (R)-1-(tetrahydrofuran-2-yl)ethylamine.

[0006] To solve the above-mentioned technical problems, the technical solution provided by the present invention is as follows: A method for preparing (R)-1-(tetrahydrofuran-2-yl)ethylamine includes the following steps: S1, in the presence of a chiral retention catalyst, (R)-tetrahydrofuran-2-carboxylic acid is esterified with a short-chain alcohol to obtain (R)-tetrahydrofuran-2-carboxylic acid ester; wherein, the chiral retention catalyst is a tertiary amine sulfonic acid inner salt type polymeric ionic liquid resin. S2,(R)-tetrahydrofuran-2-carboxylate reacts with N,O-dimethylhydroxylamine or its salt via a nucleophilic substitution reaction to yield (R)-tetrahydrofuran-N-methoxy-N-methylamide as shown in formula (Ⅰ); S3, (R)-tetrahydrofuran-N-methoxy-N-methylamide and methyl Grignard reagent undergo Grignard reaction to give (R)-1-(tetrahydrofuran-2-yl)ethyl ketone as shown in formula (II); S4, (R)-1-(tetrahydrofuran-2-yl)ethyl ketone undergoes a reducing amination reaction to obtain (R)-1-(tetrahydrofuran-2-yl)ethylamine as shown in formula (III); .

[0007] Compared with the prior art, the preparation method of (R)-1-(tetrahydrofuran-2-yl)ethylamine provided by the present invention starts from the inexpensive and readily available starting material (R)-tetrahydrofuran-2-carboxylic acid, and the target product can be obtained through four steps of esterification, nucleophilic substitution, Grignard reaction and reductive amination. It has the characteristics of simple process, high chiral center retention rate and excellent optical purity of product.

[0008] In step S1, a tertiary amine sulfonic acid inner salt type polymeric ionic liquid resin was used as a catalyst for the methyl esterification process of (R)-tetrahydrofuran-2-carboxylic acid. This catalyst not only exhibits high catalytic activity, efficiently promoting the esterification reaction, but also effectively maintains the chiral configuration of the raw materials and products, effectively avoiding chiral racemization and ensuring the optical purity of the target product. Furthermore, the catalyst possesses good stability and recyclability, allowing for repeated use and significantly reducing catalyst usage costs, thus meeting the requirements of green chemical development. Subsequent nucleophilic substitution and Grignard reactions were used to prepare a methyl ketone intermediate, followed by reductive amination to introduce an amino group. The reaction conditions at each step were mild, requiring less sophisticated equipment. The reaction process resulted in low emissions of waste and low byproduct formation, with stable overall yields and high product optical purity. This approach facilitates large-scale industrial production and demonstrates significant industrial application value and economic benefits.

[0009] It should be noted that the short-chain alcohols mentioned in this invention refer to C1-C4 alcohols. As a preferred embodiment, the short-chain alcohol is selected from any one of methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, or tert-butanol. Methanol is further preferred considering factors such as raw material cost and reactivity. In a specific embodiment of this invention, anhydrous methanol is used as the esterification reagent. Under the catalysis of a tertiary amine sulfonic acid inner salt type polymeric ionic liquid resin, it undergoes an esterification reaction with (R)-tetrahydrofuran-2-carboxylic acid, achieving a high yield and high optical purity for the target esterified product.

[0010] It should be noted that the methyl Grignard reagent described in this invention refers to an organomagnesium halide reagent containing a methyl-magnesium bond (CH3-Mg) in its molecular structure, with the general formula CH3MgX, where X is selected from Cl, bromine Br, or I. As a preferred embodiment, the methyl Grignard reagent is any one or more of methylmagnesium chloride, methylmagnesium bromide, or methylmagnesium iodide. In specific embodiments of this invention, considering both reactivity and economy, a tetrahydrofuran solution of methylmagnesium bromide is preferred.

[0011] It should be further noted that the reductive amination reaction described in step S4 of this invention can employ conventional reaction conditions and reagent systems in the art. Reductive amination refers to the reaction in which a carbonyl compound (such as an aldehyde or ketone) and an aminating agent, in the presence of a reducing agent, are converted in one step into the corresponding amine compound via an imine or imine ion intermediate. In this invention, the aminating agent can be any suitable nitrogen source capable of providing an amino group, including but not limited to ammonia, ammonia water, ammonium salts (such as ammonium formate, ammonium acetate, ammonium chloride), or organic amines; the reducing agent can be any reducing agent commonly used in reductive amination reactions in the art, including but not limited to sodium borohydride, sodium cyanoborohydride, sodium triacetoxyborohydride, or borane complexes. The reaction solvent can be a lower alcohol such as methanol, ethanol, or isopropanol, or an aqueous mixture thereof. As a preferred technical solution, this invention uses ammonium formate as the aminating agent, sodium cyanoborohydride as the reducing agent, and methanol as the solvent. This combination has advantages such as mild reaction conditions, high selectivity, and easy product purification, and is suitable for maintaining the chiral center in this system.

[0012] As a specific embodiment of the present invention, the preparation method of (R)-1-(tetrahydrofuran-2-yl)ethylamine specifically includes the following steps: S1, (R)-tetrahydrofuran-2-carboxylic acid and anhydrous methanol are subjected to methyl esterification reaction in the presence of a chiral catalyst to obtain methyl (R)-tetrahydrofuran-2-carboxylic acid. Under the conditions of S2, organic solvent and catalyst, methyl (R)-tetrahydrofuran-2-carboxylate and N,O-dimethylhydroxylamine hydrochloride were subjected to a nucleophilic substitution reaction in an inert atmosphere to obtain (R)-tetrahydrofuran-N-methoxy-N-methylamide as shown in formula (Ⅰ). S3, under an inert atmosphere, (R)-tetrahydrofuran-N-methoxy-N-methylamide and methyl Grignard reagent undergo a Grignard reaction in an organic solvent to obtain (R)-1-(tetrahydrofuran-2-yl)ethyl ketone as shown in formula (II); S4, under an inert atmosphere, (R)-1-(tetrahydrofuran-2-yl)ethyl ketone, an amination agent, and a reducing agent undergo a reductive amination reaction in an alcohol solvent to obtain (R)-1-(tetrahydrofuran-2-yl)ethylamine as shown in formula (III); S5, the (R)-1-(tetrahydrofuran-2-yl)ethylamine is reacted with an acid in an organic solvent to form a salt precipitate. After separation of the precipitate, it is dissociated by base to obtain (R)-1-(tetrahydrofuran-2-yl)ethylamine. The reaction route is as follows:

[0013] Furthermore, the tertiary amine sulfonic acid inner salt type polymeric ionic liquid resin is prepared by reacting one of imidazole, pyridine or triethylamine with sulfonate lactone or hydroxysulfonic acid to form an ionic liquid monomer, and then reacting it with formaldehyde to form a polymerization reaction.

[0014] During the research and development process, the inventors attempted a traditional esterification process, using concentrated sulfuric acid as a catalyst for the methyl esterification reaction of (R)-tetrahydrofuran-2-carboxylic acid with methanol in step S1. However, experimental results showed that this process route suffers from severe chiral racemization problems, leading to a significant decrease in the ee value of the final product.

[0015] The inventors unexpectedly discovered that using a tertiary amine sulfonic acid inner salt type polymeric ionic liquid resin as a catalyst can effectively suppress the occurrence of chiral racemization, maintaining the ee value of the final product stably above 99%, thus fully ensuring the high optical purity of the target product and meeting the stringent requirements of the pharmaceutical field for intermediates. Simultaneously, this catalyst has significant advantages over concentrated sulfuric acid: it is not highly corrosive and will not corrode reaction equipment; it also exhibits high catalytic activity, efficiently promoting the methyl esterification reaction of (R)-tetrahydrofuran-2-carboxylic acid with methanol, significantly improving the reaction conversion rate and reaction rate, and shortening the reaction cycle; furthermore, the catalyst has good stability and recyclability, and can be separated and recovered through simple filtration after the reaction, maintaining high catalytic activity even after multiple reuses, effectively reducing the cost of catalyst use and minimizing resource waste.

[0016] Furthermore, the hydroxysulfonic acid is selected from p-hydroxybenzenesulfonic acid, sulfosalicylic acid, or cresolsulfonic acid.

[0017] Furthermore, the sulfonyl lactone is 1,3-propanesulfonyl lactone.

[0018] As a specific embodiment of the present invention, the preparation method of the tertiary amine sulfonic acid inner salt type polymeric ionic liquid resin includes the following steps: Step a: Add one of imidazole, pyridine or triethylamine and sulfonyl lactone to the solvent, mix well, react for a first preset time, remove the solvent, add hydroxysulfonic acid, and continue the reaction for a second preset time to obtain the ionic liquid monomer. Step b: Mix the ionic liquid monomer with formaldehyde solution, heat to carry out polymerization reaction, and obtain tertiary amine sulfonic acid inner salt type polymeric ionic liquid resin.

[0019] For example, in step a, the solvent is selected from ethanol, acetone or ethyl acetate.

[0020] For example, the first preset time is 5~12h, and the reaction temperature is 60~100℃; the second preset time is 5~12h, and the reaction temperature is 60~100℃. The polymerization reaction temperature is 80~120℃, and the reaction time is 5~12h.

[0021] Specifically, step S1 includes the following steps: (R)-tetrahydrofuran-2-carboxylic acid, anhydrous methanol, and a chiral catalyst were mixed evenly and heated to carry out a methyl esterification reaction. The reaction was monitored by TLC until it was completed. The reaction solution was then cooled to room temperature, and the solid and liquid were separated and concentrated under reduced pressure to obtain methyl (R)-tetrahydrofuran-2-carboxylic acid.

[0022] Furthermore, in S1, the amount of the chiral retention catalyst added is 3% to 10% of the mass of (R)-tetrahydrofuran-2-carboxylic acid.

[0023] Furthermore, in S1, the temperature of the methyl esterification reaction is 60℃~100℃, and the reaction time is 4h~6h.

[0024] Furthermore, in S1, the temperature for vacuum concentration is 40°C to 70°C.

[0025] Specifically, in S1, the developing solvent monitored by TLC was petroleum ether and ethyl acetate in a volume ratio of 3:1.

[0026] Specifically, step S2 includes the following steps: Under an inert atmosphere, methyl (R)-tetrahydrofuran-2-carboxylate, N,O-dimethylhydroxylamine hydrochloride and catalyst were added to an organic solvent and a nucleophilic substitution reaction was carried out under stirring. After the reaction was completed by TLC monitoring, the solid and liquid were separated and concentrated under reduced pressure to obtain (R)-tetrahydrofuran-N-methoxy-N-methylamide.

[0027] Furthermore, in S2, the organic solvent is tetrahydrofuran.

[0028] Furthermore, in S2, the catalyst is isopropyl magnesium chloride-lithium chloride.

[0029] Further, in S2, the molar ratio of N,O-dimethylhydroxylamine hydrochloride to (R)-tetrahydrofuran-2-carboxylate is 1:0.3 to 1:1.

[0030] Furthermore, in S2, the molar ratio of the catalyst to (R)-tetrahydrofuran-2-carboxylate is 0.3:1 to 1:1.

[0031] Furthermore, in S2, the nucleophilic substitution reaction is carried out at a temperature of 10°C to 30°C for a reaction time of 4 to 6 hours.

[0032] Specifically, in S2, the developing solvent monitored by TLC was petroleum ether and ethyl acetate in a volume ratio of 3:1.

[0033] Furthermore, in S2, the temperature for vacuum concentration is 30°C to 60°C.

[0034] Specifically, step S3 includes the following steps: Under an inert atmosphere, (R)-tetrahydrofuran-N-methoxy-N-methylamide was added to an organic solvent, cooled to 0℃~5℃, and methyl Grignard reagent was slowly added. After the addition was complete, the Grignard reaction was carried out under stirring. The reaction was monitored by TLC until it was completed. The reaction was quenched by adding saturated ammonium chloride solution, extracted with ethyl acetate, washed, dried with anhydrous sodium sulfate, and the solid and liquid were separated and concentrated under reduced pressure to obtain (R)-1-(tetrahydrofuran-2-yl)ethyl ketone.

[0035] Furthermore, in S3, the methyl Grignard reagent is magnesium methyl halide.

[0036] Furthermore, in S3, the organic solvent is tetrahydrofuran.

[0037] Further, in S3, the molar ratio of the methyl Grignard reagent to (R)-tetrahydrofuran-N-methoxy-N-methylamide is 0.6:1 to 1.5:1.

[0038] Furthermore, in S3, the Grignard reaction is carried out at a temperature of 10°C to 30°C for a reaction time of 2 hours to 6 hours.

[0039] Specifically, step S4 includes the following steps: Under an inert atmosphere, (R)-1-(tetrahydrofuran-2-yl)ethyl ketone and an amination agent were added to an alcohol solvent. The temperature was lowered to 0℃~5℃, and acetic acid was slowly added. Then, a reducing agent was slowly added in batches. After the addition was completed, a reductive amination reaction was carried out under stirring. The reaction was monitored by TLC until it was completed. The reaction was quenched by adding saturated sodium bicarbonate solution. The alcohol solvent was removed under reduced pressure, and the mixture was extracted with ethyl acetate. The extract was washed, dried over anhydrous sodium sulfate, and the solid and liquid were separated. The mixture was concentrated under reduced pressure to obtain (R)-1-(tetrahydrofuran-2-yl)ethylamine.

[0040] Furthermore, in S4, the alcohol solvent is methanol.

[0041] Furthermore, in S4, the amination agent is ammonium formate.

[0042] Furthermore, in S4, the reducing agent is sodium cyanoborohydride.

[0043] Furthermore, in S4, the molar ratio of the amination agent to (R)-1-(tetrahydrofuran-2-yl)ethyl ketone is 2:1 to 4:1.

[0044] Furthermore, in S4, the molar ratio of the reducing agent to (R)-1-(tetrahydrofuran-2-yl)ethyl ketone is 1:1 to 2:1.

[0045] Furthermore, in S4, the temperature of the reductive amination reaction is 10℃~30℃, and the reaction time is 4h~9h.

[0046] Furthermore, after the reaction in step S4 is completed, a purification step in step S5 is also included. The specific purification steps are as follows: (R)-1-(tetrahydrofuran-2-yl)ethylamine crude product was dissolved in an organic solvent, cooled to 0℃~10℃, concentrated hydrochloric acid was slowly added, solid-liquid separation was performed, and the product was washed and dried to obtain (R)-1-(tetrahydrofuran-2-yl)ethylamine hydrochloride. Dissolve (R)-1-(tetrahydrofuran-2-yl)ethylamine hydrochloride in water, cool to 0℃~10℃, adjust the pH of the system to 11~12 with alkali, extract with ethyl acetate, wash the extract, dry with anhydrous sodium sulfate, separate the solid and liquid, concentrate under reduced pressure to obtain pure (R)-1-(tetrahydrofuran-2-yl)ethylamine.

[0047] Specifically, in S5, the molar ratio of concentrated hydrochloric acid to crude (R)-1-(tetrahydrofuran-2-yl)ethylamine is 0.5:1 to 2:1.

[0048] Specifically, in S5, the addition time for both concentrated hydrochloric acid and alkali is 0.15~0.5h.

[0049] Specifically, in S5, the developing solvent for TLC monitoring was petroleum ether and ethyl acetate in a volume ratio of 3:1.

[0050] Specifically, in S5, the temperature for vacuum concentration is 30°C to 60°C.

[0051] In summary, this invention provides a method for preparing (R)-1-(tetrahydrofuran-2-yl)ethylamine. This method uses readily available and inexpensive (R)-tetrahydrofuran-2-carboxylic acid as the starting material, and sequentially involves methylation, nucleophilic substitution, Grignard methylation, reductive amination, and salt precipitation-base dissociation purification steps catalyzed by a tertiary amine sulfonic acid inner salt type polymeric ionic liquid resin to obtain the target product with high optical purity. This invention, by introducing a polymeric ionic liquid resin catalyst with a specific structure, inhibits the racemization of the α-chiral center during esterification from the source, ensuring the complete preservation of the chiral configuration in each process step. The enantiomeric excess value of the final product can be stably maintained above 99%, fundamentally solving the problem of decreased optical purity caused by traditional concentrated sulfuric acid catalysis, and maintaining the ee value of the target product stably above 99%. Furthermore, the post-processing uses a salt purification method, which is simple to operate and can obtain a high optical purity product without column chromatography. This invention features a stable process, high product purity, and ease of large-scale implementation, providing an efficient and green new route for the industrial preparation of (R)-1-(tetrahydrofuran-2-yl)ethylamine. It has broad application prospects and significant industrial value in the fields of medicine, pesticides, and new materials. Attached Figure Description

[0052] Figure 1 Methyl (R)-tetrahydrofuran-2-carboxylate prepared in Example 3 of this invention 1 H NMR spectrum; Figure 2 (R)-1-(tetrahydrofuran-2-yl)ethyl ketone prepared in Example 3 of this invention 1 H NMR spectrum; Figure 3 (R)-1-(tetrahydrofuran-2-yl)ethylamine prepared in Example 3 of this invention 1 H NMR spectrum. Detailed Implementation

[0053] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0054] Unless otherwise specified, the chemical reagents and apparatus used in the following examples are commercially available.

[0055] The method for preparing (R)-1-(tetrahydrofuran-2-yl)ethylamine in the following examples includes the following steps: S1, in the presence of a chiral retention catalyst, (R)-tetrahydrofuran-2-carboxylic acid is esterified with a short-chain alcohol to obtain (R)-tetrahydrofuran-2-carboxylic acid ester; wherein, the chiral retention catalyst is a tertiary amine sulfonic acid inner salt type polymeric ionic liquid resin. S2,(R)-tetrahydrofuran-2-carboxylate reacts with N,O-dimethylhydroxylamine or its salt via a nucleophilic substitution reaction to yield (R)-tetrahydrofuran-N-methoxy-N-methylamide as shown in formula (Ⅰ); S3, (R)-tetrahydrofuran-N-methoxy-N-methylamide and methyl Grignard reagent undergo Grignard reaction to give (R)-1-(tetrahydrofuran-2-yl)ethyl ketone as shown in formula (II); S4, (R)-1-(tetrahydrofuran-2-yl)ethyl ketone undergoes a reducing amination reaction to obtain (R)-1-(tetrahydrofuran-2-yl)ethylamine as shown in formula (III); S5, the (R)-1-(tetrahydrofuran-2-yl)ethylamine is precipitated by reacting it with an acid in an organic solvent to form a salt. After separating the precipitate, it is dissociated by alkali to obtain (R)-1-(tetrahydrofuran-2-yl)ethylamine.

[0056] The synthesis route is shown below:

[0057] To better illustrate the present invention, further examples are provided below.

[0058] Example 1 This embodiment provides a method for preparing (R)-1-(tetrahydrofuran-2-yl)ethylamine: S1, (R)-tetrahydrofuran-2-carboxylic acid (1.16 g, 10 mmol) and anhydrous methanol (20 mL) were added to a single-necked flask. Under stirring, 0.039 g of tertiary amine sulfonic acid inner salt type polymeric ionic liquid resin was slowly added. The mixture was heated to 60 °C and refluxed. The reaction was stirred for 6 h. TLC monitoring (petroleum ether / ethyl acetate = 3:1, v / v) was performed until the reaction was completed. The mixture was cooled to room temperature, filtered, and concentrated under reduced pressure at 40 °C to obtain 1.19 g of crude (R)-tetrahydrofuran-2-carboxylic acid methyl ester, with a yield of 91%. It was a colorless oil and was directly used for the next step. S2, under nitrogen protection, the above crude (R)-tetrahydrofuran-2-carboxylate, anhydrous tetrahydrofuran (20 mL), N,O-dimethylhydroxylamine hydrochloride (2.90 g, 30 mmol), and isopropyl magnesium chloride-lithium chloride (2.23 mL, 2.9 mmol) were added to a three-necked flask and stirred at room temperature for 4 h. The reaction was monitored by TLC (petroleum ether / ethyl acetate = 3:1, v / v) until the reaction was complete. The mixture was filtered, and the filtrate was concentrated under reduced pressure at 30 °C to obtain 1.4 g of crude (R)-tetrahydrofuran-N-methoxy-N-methylamide, which was a pale yellow oil. This was directly used for the next step. S3, under nitrogen protection, the above crude (R)-tetrahydrofuran-N-methoxy-N-methylamide and anhydrous tetrahydrofuran (10 mL) were added to a three-necked flask. The flask was cooled to 0°C in an ice bath, and a tetrahydrofuran solution of magnesium methyl bromide (3.0 M, 4.33 mL, 13 mmol) was slowly added dropwise with stirring. The temperature was controlled at ≤8°C during the addition process, and the addition time was 30 min. After the addition was completed, the reaction was stirred at room temperature for 2 h. The reaction was monitored by TLC (petroleum ether / ethyl acetate = 3:1, v / v) until the end of the reaction. The reaction was quenched by slowly adding saturated ammonium chloride solution (20 mL) in an ice bath. The mixture was stirred for 10 min, extracted with ethyl acetate (3 × 15 mL), and the organic phases were combined. The mixture was washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure at 40°C to obtain 0.89 g of crude (R)-1-(tetrahydrofuran-2-yl)acetone, with a yield of 78%, as a colorless oil. S4, under nitrogen protection, the above-mentioned crude (R)-1-(tetrahydrofuran-2-yl)ethyl ketone, anhydrous methanol (30 mL), and ammonium formate (1 g, 15 mmol) were added to a dry three-necked flask. The flask was cooled to 0°C in an ice bath, and acetic acid (0.29 mL, 5 mmol) was slowly added dropwise with stirring for 10 min. Then, sodium cyanoborohydride (0.53 g, 8.43 mmol) was added slowly in portions, with the temperature controlled ≤8°C during the addition process and the addition time 30 min. After the addition was completed, the reaction was stirred at room temperature for 9 h. TLC monitoring (petroleum ether / ethyl acetate = The reaction was carried out at a ratio of 3:1 (v / v) until completion. Slowly add 20 mL of saturated sodium bicarbonate solution in an ice bath to quench the reaction. Stir for 10 min, remove methanol by vacuum distillation at 40 °C, extract the residue with ethyl acetate (3 × 15 mL), combine the organic phases, wash with 20 mL of saturated brine, dry with anhydrous sodium sulfate, filter, and concentrate under vacuum at 30 °C to give 0.95 g of crude (R)-1-(tetrahydrofuran-2-yl)ethylamine, which is a colorless oil. S5, the above crude (R)-1-(tetrahydrofuran-2-yl)ethylamine was dissolved in anhydrous diethyl ether (20 mL), and 6M hydrochloric acid solution (2 mL) was slowly added dropwise under ice bath. A white solid was formed, filtered, washed three times with diethyl ether, and dried to obtain 1.13 g of (R)-1-(tetrahydrofuran-2-yl)ethylamine hydrochloride, with a yield of 75%. (R)-1-(tetrahydrofuran-2-yl)ethylamine hydrochloride was dissolved in water (10 mL), and the pH was adjusted to 11 by adding 10M sodium hydroxide solution dropwise under ice bath. The solution was then extracted with ethyl acetate (3 × 15 mL). The organic phases were combined, washed with saturated brine (15 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure at 30 °C to obtain 0.78 g of pure (R)-1-(tetrahydrofuran-2-yl)ethylamine as a colorless oil with an ee of 99.2%.

[0059] Example 2 This embodiment provides a method for preparing (R)-1-(tetrahydrofuran-2-yl)ethylamine: S1, (R)-tetrahydrofuran-2-carboxylic acid (1.16 g, 10 mmol) and anhydrous methanol (20 mL) were added to a single-necked flask. Under stirring, 0.11 g of tertiary amine sulfonic acid inner salt type polymeric ionic liquid resin was slowly added. The mixture was heated to 100 °C and refluxed. The reaction was stirred for 4 h. TLC monitoring (petroleum ether / ethyl acetate = 3:1, v / v) was performed until the reaction was completed. The mixture was cooled to room temperature, filtered, and concentrated under reduced pressure at 70 °C to obtain 1.22 g of crude (R)-tetrahydrofuran-2-carboxylic acid methyl ester, with a yield of 94%. It was a colorless oil and was directly used for the next step. S2, under nitrogen protection, the above crude (R)-tetrahydrofuran-2-carboxylate, anhydrous tetrahydrofuran (20 mL), N,O-dimethylhydroxylamine hydrochloride (2.0 g, 20.5 mmol), and isopropyl magnesium chloride-lithium chloride (6.92 mL, 9 mmol) were added to a three-necked flask and stirred at room temperature for 6 h. The reaction was monitored by TLC (petroleum ether / ethyl acetate = 3:1, v / v) until the reaction was complete. The mixture was filtered, and the filtrate was concentrated under reduced pressure at 60 °C to obtain 1.45 g of crude (R)-tetrahydrofuran-N-methoxy-N-methylamide, which was a pale yellow oil. This was directly used for the next step. S3, under nitrogen protection, the above crude (R)-tetrahydrofuran-N-methoxy-N-methylamide and anhydrous tetrahydrofuran (10 mL) were added to a three-necked flask. The flask was cooled to 3°C in an ice bath. A tetrahydrofuran solution of magnesium methyl bromide (3.0 M, 2.17 mL, 6.5 mmol) was slowly added dropwise with stirring. The temperature was controlled at ≤10°C during the addition process, and the addition time was 30 min. After the addition was completed, the reaction was stirred at room temperature for 6 h. The reaction was monitored by TLC (petroleum ether / ethyl acetate = 3:1, v / v) until the reaction was completed. The reaction was quenched by slowly adding saturated ammonium chloride solution (20 mL) in an ice bath. The mixture was stirred for 10 min and extracted with ethyl acetate (3 × 15 mL). The organic phases were combined, washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure at 40°C to obtain 0.95 g of crude (R)-1-(tetrahydrofuran-2-yl)acetone, with a yield of 83%, which was a colorless oil. S4, under nitrogen protection, the above-mentioned crude (R)-1-(tetrahydrofuran-2-yl)ethyl ketone, anhydrous methanol (30 mL), and ammonium formate (2.05 g, 33 mmol) were added to a dry three-necked flask. The flask was cooled to 3°C in an ice bath, and acetic acid (0.29 mL, 5 mmol) was slowly added dropwise with stirring for 10 min. Then, sodium cyanoborohydride (1.0 g, 16 mmol) was added slowly in portions, with the temperature controlled ≤10°C during the addition process and the addition time 30 min. After the addition was completed, the reaction was stirred at room temperature for 4 h. TLC monitoring (petroleum ether / ethyl acetate = The reaction was carried out at a ratio of 3:1 (v / v) until completion. The reaction was quenched by slowly adding 20 mL of saturated sodium bicarbonate solution in an ice bath. The mixture was stirred for 10 min, and methanol was removed by vacuum distillation at 40 °C. The residue was extracted with ethyl acetate (3 × 15 mL). The organic phases were combined, washed with 20 mL of saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum at 60 °C to give 0.97 g of crude (R)-1-(tetrahydrofuran-2-yl)ethylamine, which was a colorless oil. S5, the crude (R)-1-(tetrahydrofuran-2-yl)ethylamine was dissolved in anhydrous diethyl ether (20 mL), and 6M hydrochloric acid solution (2 mL) was slowly added dropwise under ice bath. A white solid was formed, filtered, washed three times with diethyl ether, and dried to obtain 1.16 g of (R)-1-(tetrahydrofuran-2-yl)ethylamine hydrochloride, with a yield of 77%. (R)-1-(tetrahydrofuran-2-yl)ethylamine hydrochloride was dissolved in water (10 mL), and the pH was adjusted to 12 by adding 10M sodium hydroxide solution dropwise under ice bath. The solution was then extracted with ethyl acetate (3 × 15 mL). The organic phases were combined, washed with saturated brine (15 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure at 30 °C to obtain 0.80 g of pure (R)-1-(tetrahydrofuran-2-yl)ethylamine as a colorless oil with ee = 99.0%.

[0060] Example 3 This embodiment provides a method for preparing (R)-1-(tetrahydrofuran-2-yl)ethylamine: S1, (R)-tetrahydrofuran-2-carboxylic acid (1.16 g, 10 mmol) and anhydrous methanol (20 mL) were added to a single-necked flask. Under stirring, 0.072 g of tertiary amine sulfonic acid inner salt type polymeric ionic liquid resin was slowly added. The mixture was heated to 80 °C and refluxed. The reaction was stirred for 5 h. TLC monitoring (petroleum ether / ethyl acetate = 3:1, v / v) was performed until the reaction was completed. The mixture was cooled to room temperature, filtered, and concentrated under reduced pressure at 40 °C to obtain 1.27 g of crude (R)-tetrahydrofuran-2-carboxylic acid methyl ester, with a yield of 98%. It was a colorless oil and was directly used for the next step. 1 H NMR (300 MHz, DMSO-d6) δ 4.59 (s, 1H), 3.75 (d, J = 8.0 Hz, 1H), 3.7 (d, J = 8.0 Hz, 1H), 2.20 (s, 1H), 1.96 (d, J = 6.4 Hz, 2H), 1.85 (s,1H). S2, under nitrogen protection, the above crude (R)-tetrahydrofuran-2-carboxylate, anhydrous tetrahydrofuran (20 mL), N,O-dimethylhydroxylamine hydrochloride (1.05 g, 10.7 mmol), and isopropyl magnesium chloride-lithium chloride (3.46 mL, 4.5 mmol) were added to a three-necked flask and stirred at room temperature for 5 h. The reaction was monitored by TLC (petroleum ether / ethyl acetate = 3:1, v / v) until the reaction was complete. The mixture was filtered, and the filtrate was concentrated under reduced pressure at 30 °C to obtain 1.5 g of crude (R)-tetrahydrofuran-N-methoxy-N-methylamide, which was a pale yellow oil. This was directly used for the next step. S3, under nitrogen protection, the above crude (R)-tetrahydrofuran-N-methoxy-N-methylamide and anhydrous tetrahydrofuran (10 mL) were added to a three-necked flask. The flask was cooled to 5°C in an ice bath, and a tetrahydrofuran solution of magnesium methyl bromide (3.0 M, 3.1 mL, 9.3 mmol) was slowly added dropwise with stirring. The temperature was controlled at ≤10°C during the addition process, and the addition time was 30 min. After the addition was completed, the reaction was stirred at room temperature for 3 h. The reaction was monitored by TLC (petroleum ether / ethyl acetate = 3:1, v / v) until the end of the reaction. The reaction was quenched by slowly adding saturated ammonium chloride solution (20 mL) in an ice bath and stirred for 10 min. The mixture was extracted with ethyl acetate (3 × 15 mL), the organic phases were combined, washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure at 40°C to obtain 0.97 g of crude (R)-1-(tetrahydrofuran-2-yl)acetone, with a yield of 85%, as a colorless oil. 1H NMR (300 MHz, DMSO-d6) δ 4.61 (s, 1H), 3.80 (d, J = 8.0 Hz, 1H), 3.67 (d, J = 8.0 Hz, 1H), 2.24 (d, J = 6.4 Hz, 4H), 1.90 (d, J = 11.4 Hz,2H), 1.75 (s, 1H). S4, under nitrogen protection, the above-mentioned crude (R)-1-(tetrahydrofuran-2-yl)ethyl ketone, anhydrous methanol (30 mL), and ammonium formate (1.5 g, 24 mmol) were added to a dry three-necked flask. The flask was cooled to 5°C in an ice bath, and acetic acid (0.29 mL, 5 mmol) was slowly added dropwise with stirring for 10 min. Then, sodium cyanoborohydride (0.75 g, 12 mmol) was slowly added in portions, with the temperature controlled ≤10°C during the addition process and the addition time 30 min. After the addition was completed, the reaction was stirred at room temperature for 6 h. TLC monitoring (petroleum ether / ethyl acetate = The reaction was carried out at a ratio of 3:1 (v / v) until completion. The reaction was quenched by slowly adding 20 mL of saturated sodium bicarbonate solution in an ice bath. The mixture was stirred for 10 min, and methanol was removed by vacuum distillation at 40 °C. The residue was extracted with ethyl acetate (3 × 15 mL). The organic phases were combined, washed with 20 mL of saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum at 30 °C to give 0.98 g of crude (R)-1-(tetrahydrofuran-2-yl)ethylamine, which was a colorless oil. S5, the crude (R)-1-(tetrahydrofuran-2-yl)ethylamine was dissolved in anhydrous diethyl ether (20 mL), and 6M hydrochloric acid solution (2 mL) was slowly added dropwise under ice bath. A white solid was formed, filtered, washed three times with diethyl ether, and dried to obtain 1.18 g of (R)-1-(tetrahydrofuran-2-yl)ethylamine hydrochloride, with a yield of 78%. (R)-1-(tetrahydrofuran-2-yl)ethylamine hydrochloride was dissolved in water (10 mL), and the pH was adjusted to 11 by adding 10M sodium hydroxide solution dropwise under ice bath. The solution was then extracted with ethyl acetate (3 × 15 mL), the organic phases were combined, washed with saturated brine (15 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure at 30 °C to obtain 0.81 g of pure (R)-1-(tetrahydrofuran-2-yl)ethylamine as a colorless oil with an ee of 99.3%.

[0061] 1H NMR (300 MHz, DMSO-d6) δ 3.72-3.61 (m, 2H), 3.55 (d, J = 8.0 Hz,1H), 2.93 (d, J = 0.4 Hz, 3H), 1.96 (s, 1H), 1.88 (s, 1H), 1.73 (d, J = 15.2Hz, 2H), 1.11 (s, 3H). The preparation method of the tertiary amine sulfonic acid inner salt type polymeric ionic liquid resin in the above embodiments is as follows: Triethylamine 0.1 mol, 1,3 0.105 mol of propanesulfonate lactone was added to anhydrous ethanol and reacted at 80 °C for 8 h. After the reaction was completed, the solvent was removed by rotary evaporation to obtain a white solid. The solid was washed three times with petroleum ether, dried under vacuum at 80 °C for 5 h, and then 0.1 mol of p-hydroxybenzenesulfonic acid was added. The reaction was carried out at 85 °C for 4 h to obtain an ionic liquid monomer.

[0062] Formaldehyde was added at a molar ratio of 1:1 to ionic liquid monomer and formaldehyde, and the reaction was carried out at 85°C for 2 hours. The reaction solution was then vacuum dried with phosphorus pentoxide for 5 hours to obtain tertiary amine sulfonic acid inner salt type polymeric ionic liquid resin.

[0063] Comparative Example 1 This comparative example provides a method for preparing (R)-1-(tetrahydrofuran-2-yl)ethylamine, which differs from Example 3 only in that the tertiary amine sulfonic acid inner salt type polymeric ionic liquid resin is replaced with concentrated sulfuric acid; the rest are exactly the same. The specific steps are as follows: S1, (R)-tetrahydrofuran-2-carboxylic acid (1.16 g, 10 mmol) and anhydrous methanol (20 mL) were added to a single-necked flask. Under stirring, concentrated sulfuric acid (0.2 mL) was slowly added, the temperature was raised to 80 °C and refluxed, and the reaction was stirred for 5 h. The reaction was monitored by TLC (petroleum ether / ethyl acetate = 3:1, v / v) until the reaction was completed. The mixture was cooled to room temperature, methanol was removed by vacuum distillation, and the residue was neutralized by adding saturated sodium bicarbonate solution (20 mL). The mixture was stirred for 10 min and extracted with ethyl acetate (3 × 15 mL). The organic phases were combined, washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure at 40 °C to obtain 1.05 g of crude (R)-tetrahydrofuran-2-carboxylic acid methyl ester, yield 80%, which was a colorless oil and was directly used for the next step. S2, under nitrogen protection, the above crude (R)-tetrahydrofuran-2-carboxylate, anhydrous tetrahydrofuran (20 mL), N,O-dimethylhydroxylamine hydrochloride (0.87 g, 9 mmol), and isopropyl magnesium chloride-lithium chloride (2.88 mL, 3.75 mmol) were added to a three-necked flask and stirred at room temperature for 5 h. The reaction was monitored by TLC (petroleum ether / ethyl acetate = 3:1, v / v) until the reaction was complete. The mixture was filtered, and the filtrate was concentrated under reduced pressure at 30 °C to obtain 1.15 g of crude (R)-tetrahydrofuran-N-methoxy-N-methylamide, which was a deep yellow oil. This was directly used for the next step. S3, under nitrogen protection, the above crude (R)-tetrahydrofuran-N-methoxy-N-methylamide and anhydrous tetrahydrofuran (10 mL) were added to a three-necked flask. The flask was cooled to 5°C in an ice bath, and a tetrahydrofuran solution of magnesium methyl bromide (3.0 M, 2.37 mL, 7.1 mmol) was slowly added dropwise with stirring. The temperature was controlled at ≤10°C during the addition process, and the addition time was 30 min. After the addition was completed, the reaction was stirred at room temperature for 3 h. The reaction was monitored by TLC (petroleum ether / ethyl acetate = 3:1, v / v) until the end of the reaction. The reaction was quenched by slowly adding saturated ammonium chloride solution (20 mL) in an ice bath and stirred for 10 min. The mixture was extracted with ethyl acetate (3 × 15 mL), the organic phases were combined, washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure at 40°C to obtain 0.8 g of crude (R)-1-(tetrahydrofuran-2-yl)acetone, with a yield of 70%, as a pale yellow oil. S4, under nitrogen protection, the above-mentioned crude (R)-1-(tetrahydrofuran-2-yl)ethyl ketone, anhydrous methanol (30 mL), and ammonium formate (1.23 g, 20 mmol) were added to a dry three-necked flask. The flask was cooled to 5°C in an ice bath, and acetic acid (0.29 mL, 5 mmol) was slowly added dropwise with stirring for 10 min. Then, sodium cyanoborohydride (0.62 g, 10 mmol) was slowly added in portions, with the temperature controlled ≤10°C during the addition process and the addition time 30 min. After the addition was completed, the reaction was stirred at room temperature for 6 h. TLC monitoring (petroleum ether / ethyl acetate = The reaction was carried out at a ratio of 3:1 (v / v) until completion. Slowly add 20 mL of saturated sodium bicarbonate solution in an ice bath to quench the reaction. Stir for 10 min, remove methanol by vacuum distillation at 40 °C, extract the residue with ethyl acetate (3 × 15 mL), combine the organic phases, wash with 20 mL of saturated brine, dry with anhydrous sodium sulfate, filter, and concentrate under vacuum at 30 °C to give 0.90 g of crude (R)-1-(tetrahydrofuran-2-yl)ethylamine, which is a pale yellow oil. S5, the crude (R)-1-(tetrahydrofuran-2-yl)ethylamine was dissolved in anhydrous diethyl ether (20 mL), and 6M hydrochloric acid solution (2 mL) was slowly added dropwise under ice bath. A white solid was formed, filtered, washed three times with diethyl ether, and dried to obtain 1.07 g of (R)-1-(tetrahydrofuran-2-yl)ethylamine hydrochloride, with a yield of 71%. (R)-1-(tetrahydrofuran-2-yl)ethylamine hydrochloride was dissolved in water (10 mL), and the pH was adjusted to 11 by adding 10M sodium hydroxide solution dropwise under ice bath. The mixture was then extracted with ethyl acetate (3 × 15 mL), and the organic phases were combined, washed with saturated brine (15 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure at 30 °C to obtain 0.75 g of pure (R)-1-(tetrahydrofuran-2-yl)ethylamine, which was a pale yellow oily substance with ee=0 and chiral racemic character.

[0064] Comparative Example 2 This comparative example provides a method for preparing (R)-1-(tetrahydrofuran-2-yl)ethylamine, which differs from Example 3 only in that the tertiary amine sulfonic acid inner salt type polymeric ionic liquid resin is replaced with a polyvinyl imidazole acidic ionic liquid; the rest are exactly the same. The specific steps are as follows: S1, (R)-tetrahydrofuran-2-carboxylic acid (1.16 g, 10 mmol) and anhydrous methanol (20 mL) were added to a single-necked flask. Under stirring, polyvinylimidazolium acidic ionic liquid (0.11 g) was slowly added. The mixture was heated to 80 °C and refluxed. The reaction was stirred for 5 h. TLC monitoring (petroleum ether / ethyl acetate = 3:1, v / v) was performed until the reaction was complete. The mixture was cooled to room temperature, filtered, and concentrated under reduced pressure at 40 °C to obtain 1.21 g of crude (R)-tetrahydrofuran-2-carboxylic acid methyl ester, with a yield of 93%. The product was a pale yellow oil and was directly used for the next step. S2, under nitrogen protection, the above crude (R)-tetrahydrofuran-2-carboxylate, anhydrous tetrahydrofuran (20 mL), N,O-dimethylhydroxylamine hydrochloride (1 g, 10 mmol), and isopropyl magnesium chloride-lithium chloride (3.31 mL, 4.3 mmol) were added to a three-necked flask and stirred at room temperature for 5 h. The reaction was monitored by TLC (petroleum ether / ethyl acetate = 3:1, v / v) until the reaction was complete. The mixture was filtered, and the filtrate was concentrated under reduced pressure at 30 °C to obtain 1.31 g of crude (R)-tetrahydrofuran-N-methoxy-N-methylamide, which was a pale yellow oil. This was directly used for the next step. S3, under nitrogen protection, the above crude (R)-tetrahydrofuran-N-methoxy-N-methylamide and anhydrous tetrahydrofuran (10 mL) were added to a three-necked flask. The flask was cooled to 5°C in an ice bath, and a tetrahydrofuran solution of magnesium methyl bromide (3.0 M, 2.7 mL, 8.1 mmol) was slowly added dropwise with stirring. The temperature was controlled at ≤10°C during the addition process, and the addition time was 30 min. After the addition was completed, the reaction was stirred at room temperature for 3 h. The reaction was monitored by TLC (petroleum ether / ethyl acetate = 3:1, v / v) until the end of the reaction. The reaction was quenched by slowly adding saturated ammonium chloride solution (20 mL) in an ice bath and stirred for 10 min. The mixture was extracted with ethyl acetate (3 × 15 mL), the organic phases were combined, washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure at 40°C to obtain 0.92 g of crude (R)-1-(tetrahydrofuran-2-yl)acetone, with a yield of 81%, which was a pale yellow oil. S4, under nitrogen protection, the above-mentioned crude (R)-1-(tetrahydrofuran-2-yl)ethyl ketone, anhydrous methanol (30 mL), and ammonium formate (1.42 g, 23 mmol) were added to a dry three-necked flask. The flask was cooled to 5°C in an ice bath, and acetic acid (0.29 mL, 5 mmol) was slowly added dropwise with stirring for 10 min. Then, sodium cyanoborohydride (0.71 g, 11 mmol) was slowly added in portions, with the temperature controlled ≤10°C during the addition process and the addition time 30 min. After the addition was completed, the reaction was stirred at room temperature for 6 h. TLC monitoring (petroleum ether / ethyl acetate = The reaction was carried out at a ratio of 3:1 (v / v) until completion. The reaction was quenched by slowly adding 20 mL of saturated sodium bicarbonate solution in an ice bath. The mixture was stirred for 10 min, and methanol was removed by vacuum distillation at 40 °C. The residue was extracted with ethyl acetate (3 × 15 mL). The organic phases were combined, washed with 20 mL of saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum at 30 °C to give 0.93 g of crude (R)-1-(tetrahydrofuran-2-yl)ethylamine, which was a pale yellow oil. S5, the crude (R)-1-(tetrahydrofuran-2-yl)ethylamine was dissolved in anhydrous diethyl ether (20 mL), and 6M hydrochloric acid solution (2 mL) was slowly added dropwise under ice bath. A white solid was formed, filtered, washed three times with diethyl ether, and dried to obtain 1.09 g of (R)-1-(tetrahydrofuran-2-yl)ethylamine hydrochloride, with a yield of 72%. (R)-1-(tetrahydrofuran-2-yl)ethylamine hydrochloride was dissolved in water (10 mL), and the pH was adjusted to 11 by adding 10M sodium hydroxide solution dropwise under ice bath. The solution was then extracted with ethyl acetate (3 × 15 mL), the organic phases were combined, washed with saturated brine (15 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure at 30 °C to obtain 0.75 g of pure (R)-1-(tetrahydrofuran-2-yl)ethylamine, which was a pale yellow oil with an ee of 93.6%.

[0065] The preparation method of the above-mentioned polyvinylimidazolium acidic ionic liquid is as follows: Polyvinylimidazolium (PVI) (1g) was dissolved in 10mL of acetonitrile. Under ice-water bath cooling and stirring, 1.6g of trifluoromethanesulfonic acid was slowly added dropwise. After the addition was complete, the temperature was raised to 60℃ and the reaction continued for 24h. After the reaction was completed, acetonitrile and excess acid were removed by vacuum distillation. The product was washed with ethyl acetate and dried under vacuum to obtain 2.4g of polyvinylimidazolium acidic ionic liquid.

[0066] The aforementioned polyvinylimidazole is a commercially available product.

[0067] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions or improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing (R)-1-(tetrahydrofuran-2-yl)ethylamine, characterized in that, Includes the following steps: S1, in the presence of a chiral retention catalyst, (R)-tetrahydrofuran-2-carboxylic acid is esterified with a short-chain alcohol to obtain (R)-tetrahydrofuran-2-carboxylic acid ester; wherein, the chiral retention catalyst is a tertiary amine sulfonic acid inner salt type polymeric ionic liquid resin. S2,(R)-tetrahydrofuran-2-carboxylate reacts with N,O-dimethylhydroxylamine or its salt via a nucleophilic substitution reaction to yield (R)-tetrahydrofuran-N-methoxy-N-methylamide as shown in formula (Ⅰ); S3, (R)-tetrahydrofuran-N-methoxy-N-methylamide and methyl Grignard reagent undergo Grignard reaction to give (R)-1-(tetrahydrofuran-2-yl)ethyl ketone as shown in formula (II); S4, (R)-1-(tetrahydrofuran-2-yl)ethyl ketone undergoes a reducing amination reaction to obtain (R)-1-(tetrahydrofuran-2-yl)ethylamine as shown in formula (III); 。 2. The method for preparing (R)-1-(tetrahydrofuran-2-yl)ethylamine as described in claim 1, characterized in that, Specifically, the steps include the following: S1, (R)-tetrahydrofuran-2-carboxylic acid and anhydrous methanol are subjected to methyl esterification reaction in the presence of a chiral catalyst to obtain methyl (R)-tetrahydrofuran-2-carboxylic acid. Under the conditions of S2, organic solvent and catalyst, methyl (R)-tetrahydrofuran-2-carboxylate and N,O-dimethylhydroxylamine hydrochloride were subjected to a nucleophilic substitution reaction in an inert atmosphere to obtain (R)-tetrahydrofuran-N-methoxy-N-methylamide as shown in formula (Ⅰ). S3, under an inert atmosphere, (R)-tetrahydrofuran-N-methoxy-N-methylamide and methyl Grignard reagent undergo a Grignard reaction in an organic solvent to obtain (R)-1-(tetrahydrofuran-2-yl)ethyl ketone as shown in formula (II); S4, under an inert atmosphere, (R)-1-(tetrahydrofuran-2-yl)ethyl ketone, an amination agent, and a reducing agent undergo a reductive amination reaction in an alcohol solvent to obtain (R)-1-(tetrahydrofuran-2-yl)ethylamine as shown in formula (III); S5, the (R)-1-(tetrahydrofuran-2-yl)ethylamine is precipitated by reacting it with an acid in an organic solvent to form a salt. After separating the precipitate, it is dissociated by alkali to obtain (R)-1-(tetrahydrofuran-2-yl)ethylamine.

3. The method for preparing (R)-1-(tetrahydrofuran-2-yl)ethylamine as described in claim 1, characterized in that, In S1, the tertiary amine sulfonic acid inner salt type polymeric ionic liquid resin is prepared by reacting one of imidazole, pyridine or triethylamine with sulfonate lactone or hydroxysulfonic acid to form an ionic liquid monomer, and then reacting it with formaldehyde to form a polymerization reaction.

4. The method for preparing (R)-1-(tetrahydrofuran-2-yl)ethylamine as described in claim 3, characterized in that, In S1, the hydroxysulfonic acid is selected from p-hydroxybenzenesulfonic acid, sulfosalicylic acid, or cresolsulfonic acid; and / or In S1, the sulfonyl lactone is 1,3-propanesulfonyl lactone.

5. The method for preparing (R)-1-(tetrahydrofuran-2-yl)ethylamine as described in claim 2, characterized in that, In S1, the amount of the chiral retention catalyst added is 3% to 10% of the mass of (R)-tetrahydrofuran-2-carboxylic acid; and / or In S1, the temperature of the methyl esterification reaction is 60℃~100℃, and the reaction time is 4h~6h.

6. The method for preparing (R)-1-(tetrahydrofuran-2-yl)ethylamine as described in claim 2, characterized in that, In S2, the organic solvent is tetrahydrofuran; and / or In S2, the catalyst is isopropyl magnesium chloride-lithium chloride.

7. The method for preparing (R)-1-(tetrahydrofuran-2-yl)ethylamine as described in claim 2 or 6, characterized in that, In S2, the molar ratio of N,O-dimethylhydroxylamine hydrochloride to (R)-tetrahydrofuran-2-carboxylate is 1:0.3 to 1:1; and / or In S2, the molar ratio of the catalyst to methyl (R)-tetrahydrofuran-2-carboxylate is 0.3:1 to 1:1; and / or In S2, the nucleophilic substitution reaction is carried out at a temperature of 10℃ to 30℃ and for a reaction time of 4h to 6h.

8. The method for preparing (R)-1-(tetrahydrofuran-2-yl)ethylamine as described in claim 2, characterized in that, In S3, the methyl Grignard reagent is magnesium methyl halide; and / or In S3, the organic solvent is tetrahydrofuran; and / or In S3, the molar ratio of the methyl Grignard reagent to (R)-tetrahydrofuran-N-methoxy-N-methylamide is 0.6:1 to 1.5:1; and / or In S3, the temperature of the Grignard reaction is 10℃~30℃, and the reaction time is 2h~6h.

9. The method for preparing (R)-1-(tetrahydrofuran-2-yl)ethylamine as described in claim 2, characterized in that, In S4, the alcohol solvent is methanol; and / or In S4, the amination agent is ammonium formate; and / or In S4, the reducing agent is sodium cyanoborohydride.

10. The method for preparing (R)-1-(tetrahydrofuran-2-yl)ethylamine as described in claim 2 or 9, characterized in that, In S4, the molar ratio of the amination agent to (R)-1-(tetrahydrofuran-2-yl)ethyl ketone is 2:1 to 4:1; and / or In S4, the molar ratio of the reducing agent to (R)-1-(tetrahydrofuran-2-yl)ethyl ketone is 1:1 to 2:1; and / or In S4, the temperature of the reductive amination reaction is 10℃~30℃, and the reaction time is 4h~9h.

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