A kind of synthetic method of trans-4-aminomethylcyclohexanecarboxylic acid

Abstract

The invention discloses a synthesis method of trans-4-aminomethylcyclohexanecarboxylic acid, an intermediate thereof, a preparation method thereof and an application thereof. The method is simple to operate, has a stable process, has a large production capacity, is low in cost, is environmentally friendly, and the obtained trans-4-aminomethylcyclohexanecarboxylic acid has a high purity and can meet its medical application.

Description

Technical Field

[0001] The invention belongs to the field of chemical pharmacy, and specifically relates to a method for synthesizing trans-4-aminomethylcyclohexanecarboxylic acid, an intermediate in the synthesis process and application thereof. Background Art

[0002] Trans-4-aminomethylcyclohexanecarboxylic acid, also known as tranexamic acid, is a synthetic lysine derivative and an antifibrinolytic agent. It was approved by the U.S. FDA in 1986 and marketed under the trade name Cyklokapron.

[0003] Its mechanism of action is that it competitively inhibits the adsorption of plasminogen on fibrin by binding to the lysine binding site on the plasmin molecule, thereby inhibiting the activation of plasminogen and preventing the degradation of fibrinolytic protein by plasmin, thereby achieving antifibrinolytic and hemostatic effects. It is clinically used for various hemorrhagic diseases such as traumatic bleeding, excessive menstrual bleeding and postpartum hemorrhage.

[0004] In addition to its hemostatic effect, trans-4-aminomethylcyclohexanecarboxylic acid also has a whitening effect by inhibiting the plasminogen activation pathway, thereby alleviating pigmentation symptoms and can be used to treat melasma. Therefore, it is also added to daily chemical products, such as skin care products, toothpaste, etc.

[0005] Trans-4-aminomethylcyclohexanecarboxylic acid has a wide range of applications and a large amount of usage, and its research is of great significance. At present, there are many methods for synthesizing trans-4-aminomethylcyclohexanecarboxylic acid at home and abroad, mainly including:

[0006] (1) Using methyl acrylate and chloroprene as raw materials, a Diels-Alder reaction is carried out in a solvent benzene, and the obtained methyl p-chlorocyclohexenecarboxylate is subjected to cyanidation reaction with cuprous cyanide in DMF, and then cyanocyclohexene is catalytically hydrogenated using Raney nickel and hydrogen, and finally hydrolyzed, transformed, and purified to obtain trans-4-aminomethylcyclohexanecarboxylic acid. (Synthesis of a new coagulant - tranexamic acid [J]. Pharmaceutical Industry, 1972(03):31-32).

[0007] (2) 2-(Aminomethyl)-1,3-butadiene and acrylic acid are used as raw materials to undergo a Diels-Alder reaction in an alcohol solvent under the catalysis of a Lewis acid, the catalyst is removed by filtration, and then a hydrogenation reaction is carried out using a Ru(OAc)2-BINAP catalyst in a hydrogen atmosphere to obtain trans-4-aminomethylcyclohexanecarboxylic acid (CN 113956173 A).

[0008] (3) 4-Hydroxybenzoic acid is used as a raw material, and alkali and Raney nickel are used for catalytic hydrogenation, and then an esterification reaction is carried out with alcohol under the catalysis of p-toluenesulfonic acid, and then an oxidant sodium hypochlorite is used for oxidation. The obtained product is condensed with nitromethane, and then Raney nickel is used to catalyze the hydrogenation of the nitro group and the carbon-carbon double bond, and finally trans-4-aminomethylcyclohexanecarboxylic acid (CN 105017044 A) is obtained through hydrolysis and conversion.

[0009] (4) 4-aminomethylbenzoic acid is used as a raw material, a hydrogenation reaction is carried out under the catalysis of concentrated sulfuric acid and platinum dioxide, and then a configuration conversion is carried out under concentrated sulfuric acid, high temperature and high pressure, and finally the product trans-4-aminomethylcyclohexanecarboxylic acid (CN107954887A) is obtained by adjusting the pH.

[0010] (5) 1,4-cyclohexanedimethanol is used as a raw material to undergo a monohalogenation reaction with a hydrohalic acid, and the obtained compound is introduced into a trifluoroacetic acid solvent under the action of an oxidant, sodium nitrite, and oxygen is introduced to undergo an oxidation reaction. Then, liquid ammonia or ammonia water is used to perform an ammonolysis reaction, and finally potassium hydroxide is used for transformation to obtain the product, trans-4-aminomethylcyclohexanecarboxylic acid (CN110156620A).

[0011] The existing synthesis process of trans-4-aminomethylcyclohexanecarboxylic acid mainly has the following defects: route (1) uses highly toxic cuprous cyanide, which is very harmful to the human body and the environment; in route (2), the Lewis acids aluminum chloride and ferric chloride used in the Diels-Alder reaction increase the production cost and pollute the environment; some routes use the expensive and polluting Ru(OAc)2-BINAP catalyst or harsh concentrated sulfuric acid; in the currently more commonly used synthesis routes, the reaction conditions for catalytic hydrogenation of the benzene ring are harsh, requiring high pressure or expensive platinum dioxide, resulting in high production costs.

[0012] Therefore, there is an urgent need for a method that is relatively low in cost, simple to operate, and environmentally friendly and suitable for the industrial production of trans-4-aminomethylcyclohexanecarboxylic acid. Summary of the invention

[0013] In order to solve one of the above-mentioned technical problems existing in the prior art, the present invention also provides a method for synthesizing trans-4-aminomethylcyclohexanecarboxylic acid. The present invention provides a compound and its application in the preparation of trans-4-aminomethylcyclohexanecarboxylic acid. The method is simple to operate, has a stable process, high production capacity, and low cost. The obtained trans-4-aminomethylcyclohexanecarboxylic acid has high purity and can meet its medical application.

[0014] One aspect of the present invention provides a method for preparing trans-4-aminomethylcyclohexanecarboxylic acid, comprising the following steps:

[0015]

[0016] Wherein R is Cl, Br or I;

[0017] Step 1), compound A and compound B undergo an amination reaction in the presence of an initiator in an organic solvent 1 to obtain compound (I);

[0018] Step 2), compound (I) is heated to undergo a desulfurization reaction to obtain compound C;

[0019] Step 3), compound C and acrylic acid are heated to undergo a Diels-Alder reaction to obtain compound D;

[0020] Step 4), compound D is subjected to hydrogenation reaction in an organic solvent 2 to obtain compound E;

[0021] Step 5), compound E is subjected to hydrolysis reaction and conversion reaction to obtain trans-4-aminomethylcyclohexanecarboxylic acid.

[0022] In some embodiments, the initiator is one, two or three of benzoyl peroxide, lauroyl peroxide, cumene hydroperoxide, tert-butyl hydroperoxide, tert-butyl perbenzoate, methyl ethyl ketone peroxide, cyclohexanone peroxide, azobisisobutyronitrile and azobisisoheptanenitrile;

[0023] The organic solvent 1 is one, two or three of ethyl acetate, dichloromethane, acetonitrile, N,N-dimethylformamide, chloroform, tetrahydrofuran, ether, dimethyl sulfoxide and 1,4-dioxane.

[0024] In some other embodiments, a base is further added to the organic solvent 1, and the base is one, two or three of potassium carbonate, sodium carbonate, sodium bicarbonate, potassium bicarbonate, potassium hydroxide, sodium hydroxide, sodium hydride, potassium tert-butoxide, butyl lithium, and lithium diisopropylamide;

[0025] The amination reaction is carried out under heating conditions, wherein the heating temperature is 50-100°C.

[0026] In some embodiments, the temperature of the desulfurization reaction is 150-200°C.

[0027] In some embodiments, the molar ratio of the compound C to acrylic acid is 1:(3-8); and the temperature of the Diels-Alder reaction is 50-100°C.

[0028] In some other embodiments, the molar ratio of compound C to acrylic acid is 1:(3-5);

[0029] In other embodiments, the molar ratio of compound C to acrylic acid is 1:3, 1:4, 1:5, 1:6, 1:7 or 1:8.

[0030] In some embodiments, the hydrogenation reaction requires the addition of a catalytic amount of Pd—C and is carried out under a hydrogen atmosphere, wherein the catalytic amount refers to 5% to 10% of the mass of the raw material (eg, compound D).

[0031] In some other embodiments, the mass fraction of Pd—C is 5%.

[0032] In some embodiments, the organic solvent 2 is one, two or three of methanol, ethanol, n-propanol, isopropanol, tert-butanol, ethyl acetate, formic acid, acetic acid and propionic acid.

[0033] In some embodiments, the hydrolysis reaction is carried out in an acid solution under heating conditions; wherein the acid solution is one or more of a hydrochloric acid solution, a sulfuric acid solution, a phosphoric acid solution or a nitric acid solution.

[0034] In other embodiments, the concentration of the acid solution in the hydrolysis reaction is 4N to 12N, for example, 4N, 5N, 6N, 7N, 8N, 9N, 10N, 11N or 12N.

[0035] In other embodiments, the hydrolysis reaction is carried out in a hydrochloric acid solution under heating conditions; wherein the concentration of the hydrochloric acid solution is 4N to 12N, for example, 4N, 5N, 6N, 7N, 8N, 9N, 10N, 11N or 12N.

[0036] In some other embodiments, the heating condition in the hydrolysis reaction is that the temperature is maintained between 80 and 110°C.

[0037] In some embodiments, the conversion reaction is performed by heating the product obtained from the hydrolysis reaction in a high-pressure reactor in the presence of barium hydroxide and water.

[0038] In other embodiments, the ratio of the product obtained from the hydrolysis reaction to barium hydroxide is 1:(1-5), for example, 1:1, 1:2, 1:3, 1:4 or 1:5.

[0039] In other embodiments, the temperature of the conversion reaction is 150-250°C, for example, 150-200°C, 200-220°C or 220-240°C; for example, 180°C, 190°C, 200°C, 205°C, 210°C, 215°C, 220°C, 225°C, 230°C, 235°C, 240°C or 245°C.

[0040] In other embodiments, after the conversion reaction is completed, water needs to be added for dilution to adjust the pH value to 6.5-7.5.

[0041] The second aspect of the present invention provides a compound having a structure shown in formula (I),

[0042]

[0043] The third aspect of the present invention provides a method for preparing compound (I), which comprises reacting compound A with compound B in an organic solvent 1 under the action of an initiator to obtain a compound represented by formula (I):

[0044]

[0045] Wherein, R is Cl, Br or I.

[0046] In some embodiments, the initiator is one, two or three of benzoyl peroxide, lauroyl peroxide, cumene hydroperoxide, tert-butyl hydroperoxide, tert-butyl perbenzoate, methyl ethyl ketone peroxide, cyclohexanone peroxide, azobisisobutyronitrile and azobisisoheptanenitrile.

[0047] In some embodiments, the organic solvent 1 is one, two or three of ethyl acetate, dichloromethane, acetonitrile, N,N-dimethylformamide, chloroform, tetrahydrofuran, diethyl ether, dimethyl sulfoxide and 1,4-dioxane.

[0048] In some embodiments, the amination reaction further requires the addition of a base, which is one, two or three of potassium carbonate, sodium carbonate, sodium bicarbonate, potassium bicarbonate, potassium hydroxide, sodium hydroxide, sodium hydride, potassium tert-butoxide, butyl lithium and lithium diisopropylamide.

[0049] In some embodiments, the amination reaction is carried out under heating conditions, and the heating temperature is 50-100°C.

[0050] In some other embodiments, the heating temperature of the amination reaction is 50-70°C.

[0051] In some other embodiments, the heating temperature of the amination reaction is 60-80°C.

[0052] In some other embodiments, the heating temperature of the amination reaction is 70-90°C.

[0053] The third aspect of the present invention provides a use of a compound (I) in the preparation of trans-4-aminomethylcyclohexanecarboxylic acid.

[0054] In some embodiments, the using comprises the following steps:

[0055]

[0056] Step 1), compound (I) is heated to undergo a desulfurization reaction to obtain compound C;

[0057] Step 2), compound C and acrylic acid are heated to undergo a Diels-Alder reaction to obtain compound D;

[0058] Step 3), compound D is subjected to hydrogenation reaction in an organic solvent 2 to obtain compound E;

[0059] Step 4), compound E is subjected to hydrolysis reaction and conversion reaction to obtain trans-4-aminomethylcyclohexanecarboxylic acid hydrochloride.

[0060] In some embodiments, the temperature of the desulfurization reaction is 150-200°C.

[0061] In some embodiments, the molar ratio of the compound C to acrylic acid is 1:(3-8); and the temperature of the Diels-Alder reaction is 50-100°C.

[0062] In some other embodiments, the molar ratio of compound C to acrylic acid is 1:(3-5);

[0063] In other embodiments, the molar ratio of compound C to acrylic acid is 1:3, 1:4, 1:5, 1:6, 1:7 or 1:8.

[0064] In some embodiments, the hydrogenation reaction further requires the addition of a catalytic amount of Pd-C, and the reaction is carried out under a hydrogen atmosphere, wherein the catalytic amount refers to 5% to 10% of the mass of the raw material (such as compound D).

[0065] In some other embodiments, the hydrogenation reaction further requires the addition of a catalytic amount of 5% by mass of Pd-C, and the reaction is carried out under a hydrogen atmosphere.

[0066] In some embodiments, the organic solvent 2 is one or more of methanol, ethanol, n-propanol, isopropanol, tert-butanol, ethyl acetate, formic acid, acetic acid, and propionic acid.

[0067] In some embodiments, the hydrolysis reaction is carried out in an acid solution under heating conditions.

[0068] In other embodiments, the acid solution is one or more of a hydrochloric acid solution, a sulfuric acid solution, a phosphoric acid solution or a nitric acid solution.

[0069] In other embodiments, the concentration of the acid solution in the hydrolysis reaction is 4N to 12N, for example, 4N, 5N, 6N, 7N, 8N, 9N, 10N, 11N or 12N.

[0070] In other embodiments, the hydrolysis reaction is carried out in a hydrochloric acid solution under heating conditions; wherein the concentration of the hydrochloric acid solution is 4N to 12N, for example, 4N, 5N, 6N, 7N, 8N, 9N, 10N, 11N or 12N.

[0071] In some other embodiments, the heating condition in the hydrolysis reaction is that the temperature is maintained between 80 and 110°C.

[0072] In some embodiments, the conversion reaction is performed by heating the product obtained from the hydrolysis reaction in a high-pressure reactor in the presence of barium hydroxide and water.

[0073] In other embodiments, the ratio of the product obtained from the hydrolysis reaction to barium hydroxide is 1:(1-5), for example, 1:1, 1:2, 1:3, 1:4 or 1:5.

[0074] In other embodiments, the temperature of the conversion reaction is 150-250°C, for example, 150-200°C, 200-220°C or 220-240°C; for example, 180°C, 190°C, 200°C, 205°C, 210°C, 215°C, 220°C, 225°C, 230°C, 235°C, 240°C or 245°C.

[0075] In other embodiments, after the conversion reaction is completed, water needs to be added for dilution to adjust the pH value to 6.5-7.5.

[0076] Compared with the prior art, the present invention has the following advantages:

[0077] 1. The present invention utilizes the generated succinimide in situ during the synthesis process, with high atomic utilization rate, which is in line with the concept of green chemistry.

[0078] 2. The present invention does not use solvents and catalysts during the Diels-Alder reaction, and can obtain products with a higher yield, thereby greatly saving production costs.

[0079] 3. In the synthesis process, the present invention does not use highly toxic and expensive raw materials, and has high safety.

[0080] 4. The present invention has a simple method, is easy to operate, has a high yield, and is suitable for industrial production during the synthesis process.

[0081] Examples are provided below to help understand the present invention. However, it should be understood that these examples are only used to illustrate the present invention, but do not constitute any limitation. The actual protection scope of the present invention is set forth in the claims. It should be understood that any modifications and changes can be made without departing from the spirit of the present invention. DETAILED DESCRIPTION

[0082] In order to make the purpose, technical scheme and advantages of the present invention clearer, the present invention is further described in detail below in conjunction with embodiments. The specific embodiments described herein are only used to explain the present invention and are not intended to constitute any limitation of the present invention. In addition, in the following description, the description of known structures and technologies is omitted to avoid unnecessary confusion of the concept of the present invention. Such structures and technologies are also described in many publications.

[0083] Unless otherwise defined, all technical and scientific terms used in the present invention have the same meaning as commonly used in the field to which the present invention belongs. For the purpose of interpreting this specification, the following definitions will apply, and where appropriate, terms used in the singular will also include the plural form, and vice versa.

[0084] Unless the context clearly dictates otherwise, the expressions "a", "an" and "an" as used herein include plural references. For example, reference to "a cell" includes a plurality of such cells and equivalents thereof known to those skilled in the art, and so forth.

[0085] As used herein, the term "about" refers to a range of ±20% of the value that follows. In some embodiments, the term "about" refers to a range of ±10% of the value that follows. In some embodiments, the term "about" refers to a range of ±5% of the value that follows.

[0086] The solvents used herein are commercially available. The following abbreviations are used herein:

[0087] TLC: Thin layer chromatography

[0088] THF: Tetrahydrofuran

[0089] DCM: dichloromethane

[0090] DMF: dimethylformamide

[0091] eq: equivalent

[0092] Concentration N: g / L

[0093] Compounds are manually or The software names were used, and commercially available compounds were named using the supplier's catalog names.

[0094] The general synthetic route is as follows:

[0095]

[0096] The first step is amination reaction: 3-methyl-3-cyclobutene sulfone (compound A), an amination agent and an initiator are dissolved in an organic solvent, heated to reflux, and after the reaction is completed, cooled to room temperature, a base is added to the reaction solution, and the reaction is carried out at room temperature. After the reaction is completed, water is added to the reaction solution, and the aqueous phase is extracted with a suitable solution. The organic phases are combined, dried, concentrated, and separated by column chromatography to obtain the product compound (I).

[0097] The second step is the desulfurization reaction: Compound (I) is heated until it melts, and sulfur dioxide is removed under reduced pressure to obtain the product compound C.

[0098] The third step is Diels-Alder cycloaddition reaction: add excess acrylic acid to compound C, react under heating, and after the reaction is completed, remove unreacted acrylic acid under reduced pressure to obtain the cycloaddition product compound D.

[0099] The fourth step, hydrogenation reaction: dissolve compound D in an organic solvent, add 5% Pd-C, introduce hydrogen, and keep the reaction under hydrogen atmosphere. After the reaction is completed, filter and concentrate to obtain the product compound E as a white solid.

[0100] Step 5, hydrolysis reaction and conversion reaction: Compound E is added to a hydrochloric acid solution, and after the heating reaction is completed, the solution is concentrated, washed with an organic solvent, and the product is filtered; the product is added to an autoclave, and then alkali and a small amount of water are added, and the reaction is heated to convert the product into Compound F.

[0101] Example 1

[0102] (1) Amination reaction

[0103] In a 250 mL round-bottom flask, 35.1 g of 3-methyl-3-cyclobutene sulfone prepared in the laboratory, 56.7 g of N-bromosuccinimide, and 3.2 g of benzoyl peroxide were added, and then an appropriate amount of anhydrous acetonitrile was added. The mixture was placed in an oil bath at 75 ° C. and heated to reflux for 10 h. After cooling to room temperature, 73.5 g of potassium carbonate was added to the reaction solution, and the mixture was stirred at room temperature for 12 h. Water was added to the reaction solution, and the mixture was extracted with dichloromethane, concentrated under reduced pressure, and purified by column chromatography to obtain 50.0 g of compound (I) with a yield of 82.2%.

[0104] The NMR data are as follows: 1 H NMR (400MHz, DMSO) δ5.87(d,1H),4.09(d,2H),3.83(d,4H),2.67(s,4H)ppm.

[0105] (2) Desulfurization reaction

[0106] In a 500 mL round-bottom flask, 26.5 g of the product of the previous step, compound (I), was heated to 170°C until it melted, and sulfur dioxide was removed under reduced pressure to obtain 17.7 g of compound C with a yield of 92.6%.

[0107] The NMR data are as follows: 1 H NMR (500MHz, CDCl3) δ6.36(dd,1H),5.36(d,1H),5.20-5.08(m,2H),4.95(s,1H),4.27(s,2H),2.74(s,4H)ppm.

[0108] (3) Diels-Alder cycloaddition

[0109] To 28.3 g of compound C was added 98.7 g (8 eq) of acrylic acid, and the reaction was carried out at 80° C. for 2 h. After the reaction was completed, unreacted acrylic acid was removed under reduced pressure to obtain 38.6 g of compound D with a yield of 95.1%.

[0110] The NMR data are as follows: 1 H NMR (500MHz, CDCl3) δ5.58(d,1H),4.01(s,2H),2.72(s,4H),2.60-2.46(m,1H),2.35-2.15(m,2H),2.05(t,3H),1.69(ddd,1H)ppm.

[0111] (4) Hydrogenation reaction

[0112] 21.0 g of compound D was dissolved in a mixed solution of ethanol and acetic acid, 2.1 g of 5% Pd-C was added, hydrogen was continuously introduced, the reaction was carried out for 2 days, the mixture was filtered, concentrated, and ethyl acetate was added to obtain 19.1 g of white solid compound E with a yield of 90.1%.

[0113] The NMR data are as follows: 1 H NMR (500MHz, CDCl3) δ3.41(d,2H),2.71(s,4H),2.63-2.57(m,1H),2.07(dd,2H),1.81(d,1H),1.56-1.47(m,4H),1.30(dd,2H)ppm.

[0114] (5) Hydrolysis and transformation

[0115] Immerse 37.8g of compound E in a 6N hydrochloric acid solution, heat in an oil bath at 115°C and reflux for 10h. After the reaction is completed, concentrate, wash the solid with acetone, and filter to obtain 26.0g of 4-aminomethylcyclohexanecarboxylic acid hydrochloride. Place it in a high-pressure reactor with 78.0g of barium hydroxide in a weight ratio of 1:3, add an appropriate amount of water, heat to 220°C, react for 10h, dilute with water, adjust the pH value to 6.5-7.5 with dilute hydrochloric acid, and filter to obtain 20.0g of trans-4-aminomethylcyclohexanecarboxylic acid (compound F), with a yield of 80.7%. The NMR data are as follows: 1 H NMR(400MHz,D2O)δ2.86(t,2H),2.12(tt,1H),1.89-2.02(m,2H),1.74-1.89(m,2H),1.55-1.73(m,1H),1.37(qd,2H),1.06(qd,2H)ppm.

[0116] Example 2

[0117] Amination reaction

[0118] In a 500 mL round-bottom flask, 20.0 g of 3-methyl-3-cyclobutene sulfone prepared in the laboratory, 24.2 g of N-chlorosuccinimide, and 1.8 g of benzoyl peroxide were added, and then an appropriate amount of anhydrous acetonitrile was added. The mixture was placed in an oil bath at 75 ° C. and heated to reflux for 14 h. After cooling to room temperature, 41.8 g of potassium carbonate was added to the reaction solution, and the mixture was stirred at room temperature for 12 h. Water was added to the reaction solution, and the mixture was extracted with dichloromethane, concentrated under reduced pressure, and purified by column chromatography to obtain 27 g of compound (I) with a yield of 77.8%.

[0119] Example 3

[0120] Amination reaction

[0121] In a 500 mL round-bottom flask, 40.0 g of 3-methyl-3-cyclobutene sulfone prepared in the laboratory, 81.7 g of N-iodosuccinimide, and 3.7 g of benzoyl peroxide were added, and then an appropriate amount of anhydrous acetonitrile was added. The mixture was placed in an oil bath at 75 ° C. and heated to reflux for 10 h. After cooling to room temperature, 83.6 g of potassium carbonate was added to the reaction solution, and the mixture was stirred at room temperature for 12 h. Water was added to the reaction solution, and the mixture was extracted with dichloromethane, concentrated under reduced pressure, and purified by column chromatography to obtain 57.6 g of compound (I) with a yield of 83.0%.

[0122] The above description is only a specific implementation mode of the present invention and cannot be used to limit the protection scope of the present invention. Any modification, equivalent substitution, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing trans-4-aminomethylcyclohexanecarboxylic acid, comprising the following steps: Wherein R is Cl, Br or I; Step 1), compound A and compound B undergo an amination reaction in the presence of an initiator in an organic solvent 1 to obtain compound (I); the initiator is benzoyl peroxide; the organic solvent 1 is one, two or three of ethyl acetate, dichloromethane, acetonitrile, N,N-dimethylformamide, chloroform, tetrahydrofuran, ether, dimethyl sulfoxide, 1,4-dioxane; wherein a base is further added to the organic solvent 1, and the base is one, two or three of potassium carbonate, sodium carbonate, sodium bicarbonate, potassium bicarbonate, potassium hydroxide, sodium hydroxide, sodium hydride, potassium tert-butoxide, butyl lithium, and lithium diisopropylamide; the amination reaction is carried out under heating conditions, wherein the heating temperature is 50-100° C.; Step 2), compound (I) is heated to undergo a desulfurization reaction to obtain compound C; the desulfurization reaction temperature is 150-200°C; Step 3), compound C and acrylic acid are heated to undergo Diels-Alder reaction to obtain compound D; the molar ratio of compound C to acrylic acid is 1:(3-8); the temperature of the Diels-Alder reaction is 50-100°C; Step 4), compound D is hydrogenated in organic solvent 2 to obtain compound E; the hydrogenation reaction also requires the addition of a catalytic amount of Pd-C, and the reaction is carried out under a hydrogen atmosphere; Step 5), compound E undergoes hydrolysis reaction and conversion reaction to obtain trans-4-aminomethylcyclohexanecarboxylic acid; the hydrolysis reaction is carried out in an acidic solution, the concentration of the acidic solution is 4N to 12N, and the heating condition in the hydrolysis reaction is to maintain the temperature between 80 and 110°C; The conversion reaction is a reaction of the product obtained by the hydrolysis reaction in the presence of barium hydroxide and water under heating conditions in a high-pressure reactor, and the temperature of the conversion reaction is 150-250°C.

2. A compound having a structure represented by formula (I), 3. A method for preparing the compound (I) as shown in claim 2, the method comprising reacting compound A with compound B in an organic solvent 1 under the action of an initiator to obtain a compound shown in formula (I): in, R is Cl, Br or I; The initiator is benzoyl peroxide; the organic solvent 1 is one, two or three of ethyl acetate, dichloromethane, acetonitrile, N,N-dimethylformamide, chloroform, tetrahydrofuran, ether, dimethyl sulfoxide and 1,4-dioxane; wherein a base needs to be added to the organic solvent 1, and the base is one, two or three of potassium carbonate, sodium carbonate, sodium bicarbonate, potassium bicarbonate, potassium hydroxide, sodium hydroxide, sodium hydride, potassium tert-butoxide, butyl lithium and lithium diisopropylamide; the amination reaction is carried out under heating conditions, wherein the heating temperature is 50-100°C.

4. Use of the compound (I) as claimed in claim 2 in the preparation of trans-4-aminomethylcyclohexanecarboxylic acid; The application comprises the following steps: Step 1), compound (I) is heated to undergo a desulfurization reaction to obtain compound C; the desulfurization reaction temperature is 150-200°C; Step 2), compound C and acrylic acid are heated to undergo Diels-Alder reaction to obtain compound D; the molar ratio of compound C to acrylic acid is 1:(3-8); the temperature of the Diels-Alder reaction is 50-100°C; Step 3), compound D is hydrogenated in organic solvent 2 to obtain compound E; the hydrogenation reaction also requires the addition of a catalytic amount of Pd-C, and the reaction is carried out under a hydrogen atmosphere; Step 4), compound E is subjected to hydrolysis reaction and conversion reaction to obtain trans-4-aminomethylcyclohexanecarboxylic acid; the hydrolysis reaction is carried out in an acidic solution, the concentration of the acidic solution is 4N to 12N, and the heating condition in the hydrolysis reaction is that the temperature is maintained between 80 and 110°C; The conversion reaction is a reaction of the product obtained by the hydrolysis reaction in the presence of barium hydroxide and water under heating conditions in a high-pressure reactor, and the temperature of the conversion reaction is 150-250°C.

Images