Preparation method of substituted cyclopentadiene

Abstract

The invention provides a preparation method of substituted cyclopentadiene. The method comprises the following steps: in the presence of trifluoroacetic acid, reacting a compound in a formula A to obtain a compound in a formula I; in the imgabs0 #, R is selected from a hydrogen atom or a saturated or unsaturated straight chain or branched chain alkyl group containing 1 to 20 carbon atoms; r'is selected from saturated or unsaturated linear chain or branched chain alkyl containing 1-20 carbon atoms; the reaction temperature is not higher than 40 DEG C. According to the method, the consumption of acid in the reaction process can be greatly reduced, complete conversion of the tertiary alcohol intermediate can be realized only by adding a small amount of acid, heating is not needed, and the energy consumption is reduced. Meanwhile, the proportion of endotype products in the reaction product is increased.

Description

Technical Field

[0001] The present invention belongs to the field of cycloalkane preparation, and particularly relates to a method for preparing substituted cyclopentadiene. Background Art

[0002] Compounds with a cyclopentadiene ring structure are one of the important ligands in organic synthesis. After forming a compound with a transition metal atom, such ligands can be widely applied in the catalytic field. In particular, metallocene compounds formed with metals of the fourth sub-group (titanium, zirconium, hafnium) can catalyze olefin polymerization in the presence of a cocatalyst, and the performance of the resulting polymer is much better than that of the polymer obtained by traditional catalysts. At the same time, such metallocene catalysts have a high degree of controllability, and the electronic effect and steric effect of the polymerization active center can be balanced by adjusting the substituents on the ligand, thereby regulating the polymerization behavior and polymer performance. Therefore, the synthesis of cyclopentadiene compounds with different substituents is of great significance for the olefin polymerization industry and the theoretical research of polymerization catalysis.

[0003] The preparation of polysubstituted cyclopentadiene by the reaction of Grignard reagent (alkyl magnesium halide) with cyclopentenone is one of the most commonly used methods. The Grignard reagent reacts with cyclopentenone to form the magnesium salt of cyclopentenol, and then in the presence of a reagent containing an active hydrogen atom (such as water), a tertiary alcohol intermediate is formed, and a double bond is formed by dehydration to obtain polysubstituted cyclopentadiene. According to different dehydration conditions, it can be divided into two types: dehydration under the action of an acid and dehydration by heating.

[0004]

[0005] The first type: US5434324A describes a method for preparing alkyl-substituted cyclopentadiene by reacting cyclopentenone with a Grignard reagent, followed by hydrolysis and dehydroxylation with an aqueous solution of an equivalent organic carboxylic acid. DE19900732A1 reports a method for obtaining alkyl-substituted cyclopentadiene by treating the reaction mixture of cyclopentenone and a Grignard reagent with an aqueous solution of an inorganic acid.

[0006] The second type: US5856541A reports that after the reaction of a Grignard reagent with cyclopentenone, an equivalent amount of water is added, and dehydroxylation is carried out by heating under reflux to obtain alkyl-substituted cyclopentadiene. CN101993330A reports that after the reaction of a Grignard reagent with cyclopentenone, an equivalent amount of an alcohol or phenol containing an active hydrogen atom is added, and dehydroxylation is carried out by heating under reflux to obtain alkyl-substituted cyclopentadiene.

[0007] The last step of the reaction involves the elimination of a hydrogen atom to form a double bond. If the hydrogen comes from a substituent, an exocyclic double bond product (exo, exo-form) is formed. If the hydrogen comes from the cyclopentadiene ring, an endocyclic double bond product (endo, endo-form) is obtained. The metallocene compound is produced from the endo-form product, rather than the exo-form product. To improve the atom economy of the reaction, reduce the formation of unnecessary by-products, and ease the difficulty of the subsequent reaction work-up process, a method for producing fewer exo-form products is needed. Summary of the Invention

[0008] In view of the deficiencies of the prior art, the present invention provides a method for preparing a compound of formula I, comprising the following steps: in the presence of an acid, a compound of formula A reacts to obtain a compound of formula I;

[0009]

[0010] wherein, R is selected from a hydrogen atom or a saturated or unsaturated straight-chain or branched-chain alkyl group containing 1-20 carbon atoms;

[0011] R' is selected from a saturated or unsaturated straight-chain or branched-chain alkyl group containing 1-20 carbon atoms;

[0012] The acid is selected from trifluoroacetic acid;

[0013] The temperature of the reaction is not higher than 40 °C.

[0014] According to an embodiment of the present invention, the molar ratio of the acid to the compound of formula A is 0.2:1 to 0.5:1, such as 0.3:1, 0.35:1, 0.4:1, 0.45:1.

[0015] According to an embodiment of the present invention, the temperature of the reaction can be 5 °C, 10 °C, 15 °C, 20 °C, 25 °C (room temperature), 30 °C or 35 °C.

[0016] According to an embodiment of the present invention, the reaction system contains an ether solvent. For example, the ether solvent is selected from any one of diethyl ether, tetrahydrofuran, 1,4-dioxane, and ethylene glycol dimethyl ether.

[0017] According to an embodiment of the present invention, the reaction system further contains water and a C6-C10 alkane solvent. For example, the C6-C10 alkane solvent is n-hexane, n-octane or heptane, etc.

[0018] According to an embodiment of the present invention, the acid is added to the reaction system in a dropwise manner; preferably, the temperature of the system during the dropwise addition is 5-15 °C, preferably 10 °C.

[0019] According to an embodiment of the present invention, the reaction time is not less than 0.5 h, such as 0.5-3 h.

[0020] According to an embodiment of the present invention, R is selected from a hydrogen atom or a saturated or unsaturated straight-chain or branched-chain alkyl group having 1 to 10 carbon atoms, preferably a saturated or unsaturated straight-chain or branched-chain alkyl group having 1 to 4 carbon atoms. For example, R is methyl, ethyl, propyl or butyl.

[0021] According to an embodiment of the present invention, R' is selected from a hydrogen atom or a saturated or unsaturated straight-chain or branched-chain alkyl group having 1 to 10 carbon atoms, preferably a saturated or unsaturated straight-chain or branched-chain alkyl group having 1 to 4 carbon atoms. For example, R' is methyl, ethyl, propyl or butyl.

[0022] According to an embodiment of the present invention, the compound of formula A is obtained by reacting the compound of formula B with water;

[0023]

[0024] Preferably, the reaction system further contains an ether solvent and n-hexane; the ether solvent has the definition as shown above.

[0025] According to an embodiment of the present invention, the compound of formula B is obtained by reacting the compound of formula C with a Grignard reagent;

[0026]

[0027] Wherein, X is any one of Cl, Br, and I;

[0028] Preferably, the above reaction is carried out in an ether solvent; the ether solvent has the definition as shown above;

[0029] Preferably, the molar ratio of the Grignard reagent to the compound of formula C is (1.0 - 1.2):1;

[0030] Preferably, the concentration of the compound of formula C in the ether solvent is 1.5 - 4.0 mol / L, for example, 2 - 4.0 mol / L.

[0031] According to an embodiment of the present invention, the molar percentage of the endo product of the compound of formula I prepared is not less than 80%, preferably not less than 82%.

[0032] According to a preferred embodiment of the present invention, the preparation method of the compound of formula I includes: reacting the compound of formula C with a Grignard reagent to obtain the compound of formula B, reacting the compound of formula B with water to obtain the compound of formula A, and reacting the compound of formula A in the presence of trifluoroacetic acid to obtain the compound of formula I;

[0033] The synthetic route is as follows:

[0034]

[0035] The reaction system contains an ether solvent, and preferably the ether solvent is any one of diethyl ether, tetrahydrofuran, 1,4-dioxane, and ethylene glycol dimethyl ether;

[0036] The molar ratio of the compound of formula C to trifluoroacetic acid is 1:(0.2 - 0.5), such as 1:0.2, 1:0.3, 1:0.4, 1:0.5;

[0037] The temperature for the reaction of the compound of formula A is not higher than 40 °C.

[0038] According to a more preferred embodiment of the present invention, the preparation method of the compound of formula I comprises the following steps:

[0039] a) Under a nitrogen atmosphere, add a Grignard reagent (1.0 - 1.2 eq) to a reaction flask, dissolve the compound of formula C (1.0 eq) in an ether solvent (2.0 - 4.0 M) and add it to a constant pressure dropping funnel, and stir and dropwise add at 0 - 10 °C; after the dropping is completed, raise the temperature to room temperature and react for 1 - 3 h;

[0040] b) Add n-hexane to the reaction system of step a) (the added amount of n-hexane halves the concentration of the reaction system), and slowly dropwise add H 2 O (the same volume as the ether) at 10 - 20 °C, and stir at room temperature for 0.5 h; then slowly dropwise add trifluoroacetic acid (0.2 - 0.5 eq) at 10 - 20 °C, and raise the temperature to room temperature and stir for 0.5 - 2 h;

[0041] c) Separate the liquid, extract the aqueous phase twice with n-hexane, combine the organic phases, and wash twice with saturated sodium carbonate.

[0042] The inventors found that when the acid concentration in the system is too high, the alkyl-substituted cyclopentadiene compound has poor stability, and the in-ring double bond product is easily isomerized into an exo-ring double bond by-product, and may also be transformed into a compound with a high boiling point. However, using an individual strongly acidic organic acid can obtain a better dehydration effect. The inventors also found that high temperature is also unfavorable for the stability of the substituted cyclopentadiene compound, and it is easily transformed into a compound with a high boiling point. In the first dehydration method mentioned in the background art, the amount of acid used is more than equivalent. In addition to the above problems, there is also a problem of large material consumption; in the second dehydration method, heating is required, resulting in high energy consumption. These are not conducive to obtaining a substituted cyclopentadiene with a high proportion of endo-product.

[0043] Beneficial effects

[0044] Compared with the prior art, trifluoroacetic acid has an outstanding catalytic dehydration effect in this reaction, which can greatly reduce the amount of acid used in the reaction process. Only a small amount of acid needs to be added to achieve the complete conversion of the tertiary alcohol intermediate, and heating is not required, reducing the energy consumption. At the same time, the proportion of the in-ring double bond product (i.e., the endo-product) in the reaction product obtained is increased.

[0045] In addition, it is not necessary to isolate the tertiary alcohol obtained by reacting the Grignard reagent with the substituted cyclopentenone. By directly adding less than an equivalent amount of acid, the complete conversion of the tertiary alcohol intermediate can be achieved, making the reaction for preparing the substituted cyclopentadiene more continuous and with low material consumption. Specific Embodiments

[0046] The technical solutions of the present invention will be further described in detail below in conjunction with specific embodiments. It should be understood that the following embodiments are only for illustrative explanation of the present invention and should not be construed as limiting the protection scope of the present invention. All technologies implemented based on the above content of the present invention are covered within the scope of protection intended by the present invention.

[0047] Unless otherwise specified, the raw materials and reagents used in the following examples are commercially available products or can be prepared by known methods.

[0048] Example 1 Preparation of l-butyl-3-methylcyclopentadiene

[0049] Place a magnetic stirrer (equipped with a constant pressure dropping funnel) in a well-dried 500 mL three-necked flask, evacuate, and replace with nitrogen three times. Add n-butylmagnesium chloride (2M in THF, 1.1eq, 0.11mol, 55mL) to the three-necked flask, and add 3-methyl-2-cyclopenten-1-one (0.1mol, 9.8mL) and dry THF (50mL) to the constant pressure dropping funnel. Place the three-necked flask in a low-temperature reactor at 0 °C, stir and drip. After the dripping is completed, raise the temperature to room temperature and stir for 2 h. Monitor the reaction by TLC, and there is no remaining cyclopentenone. Add 100 mL of n-hexane, cool to 10 °C, slowly drip 40 mL of deionized water, raise the temperature to room temperature and stir for 0.5 h. Then cool to 10 °C, slowly drip trifluoroacetic acid (0.4eq, 0.04mol, 5.6mL), raise the temperature to room temperature and stir for 0.5 h. Monitor the reaction by TLC, and there is no remaining tertiary alcohol intermediate. Separate the liquid, add a certain amount of dilute hydrochloric acid to the aqueous phase to break the emulsion, extract twice with 20 mL of n-hexane, combine the organic phases, and wash twice with saturated Na 2 CO 3 aqueous solution twice, wash twice with saturated NaCl aqueous solution, add anhydrous Na 2 SO 4 to dry, and rotary evaporate to remove the solvent to obtain the product l-butyl-3-methylcyclopentadiene.

[0050] The molar ratio of the endo product to the exo product in the product system was measured by GC to be 83 / 17.

[0051] Example 2 Preparation of l-propyl-3-methylcyclopentadiene

[0052] Place a magnetic stir bar (add a constant pressure dropping funnel) in a 500 mL three-necked flask that has been fully dried. Evacuate the air and replace it with nitrogen three times. Add n-propylmagnesium chloride (2 M in THF, 1.1 eq, 0.11 mol, 55 mL) to the three-necked flask, and add 3-methyl-2-cyclopenten-1-one (0.1 mol, 9.8 mL) and dry THF (40 mL) to the constant pressure dropping funnel. Place the three-necked flask in a low-temperature reactor at 0 °C, stir and add dropwise. After the addition is complete, raise the temperature to room temperature and stir for 2 h. Monitor the reaction by TLC, and there is no remaining cyclopentenone. Add 100 mL of n-hexane, cool to 15 °C, slowly add 40 mL of deionized water dropwise, raise the temperature to room temperature and stir for 0.5 h. Then cool to 15 °C again, slowly add trifluoroacetic acid (0.4 eq, 0.04 mol, 5.6 mL) dropwise, raise the temperature to room temperature and stir for 1 h. Monitor the reaction by TLC, and there is no remaining tertiary alcohol intermediate. Separate the layers, add dilute hydrochloric acid to the aqueous phase to break the emulsion, extract twice with 20 mL of n-hexane, combine the organic phases, and wash twice with saturated Na 2 CO 3 aqueous solution, wash twice with saturated NaCl aqueous solution, add anhydrous Na 2 SO 4 to dry, rotary evaporate to remove the solvent to obtain the product 1-propyl-3-methylcyclopentadiene.

[0053] The molar ratio of the endo product to the exo product in the product system was measured by GC to be 84 / 16.

[0054] Example 3 Preparation of 1-butyl-3-methylcyclopentadiene

[0055] Place a magnetic stir bar (add a constant pressure dropping funnel) in a 500 mL three-necked flask that has been fully dried. Evacuate the air and replace it with nitrogen three times. Add n-butylmagnesium chloride (2 M in THF, 1.1 eq, 0.11 mol, 55 mL) to the three-necked flask, and add 3-methyl-2-cyclopenten-1-one (0.1 mol, 9.8 mL) and dry THF (40 mL) to the constant pressure dropping funnel. Place the three-necked flask in a low-temperature reactor at 0 °C, stir and add dropwise. After the addition is complete, raise the temperature to room temperature and stir for 2 h. Monitor the reaction by TLC, and there is no remaining cyclopentenone. Add 100 mL of n-hexane, cool to 10 °C, slowly add 40 mL of deionized water dropwise, raise the temperature to room temperature and stir for 0.5 h. Then cool to 10 °C again, slowly add trifluoroacetic acid (0.2 eq, 0.02 mol, 2.8 mL) dropwise, raise the temperature to room temperature and stir for 2 h. Monitor the reaction by TLC, and there is a small amount of remaining tertiary alcohol intermediate. Separate the layers, add dilute hydrochloric acid to the aqueous phase to break the emulsion, extract twice with 20 mL of n-hexane, combine the organic phases, and wash twice with saturated Na 2 CO 3 aqueous solution, wash twice with saturated NaCl aqueous solution, add anhydrous Na 2 SO 4Dry it, remove the solvent by rotary evaporation to obtain the product 1-butyl-3-methylcyclopentadiene.

[0056] The molar ratio of the endo product to the exo product in the product system was measured by GC to be 83 / 17.

[0057] Example 4 Preparation of 1-butyl-3-methylcyclopentadiene

[0058] Place a magnetic stir bar (add a constant pressure dropping funnel) in a thoroughly dried 500 mL three-necked flask, evacuate it, and replace it with nitrogen three times. Add n-butylmagnesium chloride (2M in THF, 1.2 eq, 0.12 mol, 60 mL) to the three-necked flask, and add 3-methyl-2-cyclopenten-1-one (0.1 mol, 9.8 mL) and dry THF (40 mL) to the constant pressure dropping funnel. Place the three-necked flask in a low-temperature reactor at 0 °C, stir and add dropwise. After the addition is complete, raise the temperature to room temperature and stir for 2 h. Monitor the reaction by TLC. There is no remaining cyclopentenone. Add 100 mL of n-hexane, cool to 10 °C, slowly add 40 mL of deionized water dropwise, raise the temperature to room temperature and stir for 0.5 h. Then cool to 10 °C, slowly add trifluoroacetic acid (0.5 eq, 0.05 mol, 7 mL), raise the temperature to room temperature and stir for 0.5 h. Monitor the reaction by TLC. There is no remaining tertiary alcohol intermediate. Separate the layers. Add dilute hydrochloric acid to the aqueous phase to break the emulsion, extract twice with 20 mL of n-hexane, combine the organic phases, and wash twice with saturated Na 2 CO 3 aqueous solution twice and wash twice with saturated NaCl aqueous solution. Add anhydrous Na 2 SO 4 Dry it, remove the solvent by rotary evaporation to obtain the product 1-butyl-3-methylcyclopentadiene.

[0059] The molar ratio of the endo product to the exo product in the product system was measured by GC to be 82 / 18.

[0060] Comparative Example 1 Preparation of 1-propyl-3-methylcyclopentadiene

[0061] Place a magnetic stir bar (add a dropping funnel with constant pressure) in a 500 mL three-necked flask that has been fully dried, evacuate the air, and displace it with nitrogen three times. Add n-propylmagnesium chloride (2M in THF, 1.1 eq, 0.11 mol, 55 mL) to the three-necked flask, and add 3-methyl-2-cyclopenten-1-one (0.1 mol, 9.8 mL) and dry THF (40 mL) to the dropping funnel with constant pressure. Place the three-necked flask in a low-temperature reactor at 0 °C, stir and add dropwise. After the addition is complete, raise the temperature to room temperature and stir for 2 h. Monitor the reaction by TLC, and there is no remaining cyclopentenone. Add 100 mL of n-hexane, cool to 15 °C, slowly add 40 mL of deionized water dropwise, raise the temperature to room temperature and stir for 0.5 h. Then cool to 15 °C again, slowly add trifluoromethanesulfonic acid (0.4 eq, 0.04 mol, 3.5 mL) dropwise, raise the temperature to room temperature and stir for 1 h. Monitor the reaction by TLC, and there is no remaining tertiary alcohol intermediate. Separate the layers, add dilute hydrochloric acid to the aqueous phase to break the emulsion, extract twice with 20 mL of n-hexane, combine the organic phases, and wash twice with saturated Na 2 CO 3 aqueous solution, wash twice with saturated NaCl aqueous solution, add anhydrous Na 2 SO 4 to dry, rotary evaporate to remove the solvent to obtain the product 1-propyl-3-methylcyclopentadiene.

[0062] The molar ratio of the endo product to the exo product in the product system was measured by GC to be 69 / 31.

[0063] Comparative Example 2 Preparation of 1-butyl-3-methylcyclopentadiene

[0064] Place a magnetic stir bar (add a dropping funnel with constant pressure) in a 500 mL three-necked flask that has been fully dried, evacuate the air, and displace it with nitrogen three times. Add n-butylmagnesium chloride (2M in THF, 1.2 eq, 0.12 mol, 60 mL) to the three-necked flask, and add 3-methyl-2-cyclopenten-1-one (0.1 mol, 9.8 mL) and dry THF (40 mL) to the dropping funnel with constant pressure. Place the three-necked flask in a low-temperature reactor at 0 °C, stir and add dropwise. After the addition is complete, raise the temperature to room temperature and stir for 2 h. Monitor the reaction by TLC, and there is no remaining cyclopentenone. Add 100 mL of n-hexane, cool to 10 °C, slowly add 40 mL of deionized water dropwise, raise the temperature to room temperature and stir for 0.5 h. Then cool to 10 °C again, add p-toluenesulfonic acid (0.5 eq, 0.05 mol, 8.6 g) in two batches, raise the temperature to room temperature and stir for 0.5 h. Monitor the reaction by TLC, and there is no remaining tertiary alcohol intermediate. Separate the layers, add dilute hydrochloric acid to the aqueous phase to break the emulsion, extract twice with 20 mL of n-hexane, combine the organic phases, and wash twice with saturated Na 2 CO 3 aqueous solution, wash twice with saturated NaCl aqueous solution, add anhydrous Na 2 SO 4Dry it, remove the solvent by rotary evaporation to obtain the product l-butyl-3-methylcyclopentadiene.

[0065] The molar ratio of the endo product to the exo product in the product system was measured by GC to be 73 / 27.

[0066] Comparative Example 3 Preparation of l-butyl-3-methylcyclopentadiene (implemented according to the scheme of Patent Document US5434324A)

[0067] Place a magnetic stir bar (add a constant pressure dropping funnel) in a thoroughly dried 500 mL three-necked flask, evacuate, and replace with nitrogen three times. Add n-butylmagnesium chloride (2M in THF, 1.1eq, 0.11mol, 55mL) to the three-necked flask, and add 3-methyl-2-cyclopenten-1-one (9.8mL, 0.1mol) and dry THF (40mL) to the constant pressure dropping funnel. Place the three-necked flask in a low-temperature reactor at -10 °C, stir and add dropwise. After the addition is complete, react for 0.5 h, then raise the temperature to room temperature and react for 2.5 h. At 0 °C, add an acetic acid aqueous solution (2eq, 0.2mol, 12mL acetic acid + 40mL water) dropwise to the reaction solution, then raise the temperature to room temperature and stir for 2 h. Separate and remove the aqueous phase, wash the organic phase with saturated Na 2 CO 3 aqueous solution until the aqueous phase is alkaline, wash with saturated NaCl twice, and dry with anhydrous Na 2 SO 4 Dry it, remove the solvent by rotary evaporation to obtain the product l-butyl-3-methylcyclopentadiene.

[0068] The molar ratio of the endo product to the exo product in the product system was measured by GC to be 72 / 28.

[0069] Comparative Example 4 Preparation of l-butyl-3-methylcyclopentadiene (implemented according to the scheme of Patent Document US5856541A)

[0070] Place a magnetic stir bar (add a constant pressure dropping funnel) in a thoroughly dried 500 mL three-necked flask, evacuate, and replace with nitrogen three times. Add n-butylmagnesium chloride (2M in THF, 0.11mol, 55mL) to the three-necked flask, and add 3-methyl-2-cyclopenten-1-one (0.1mol, 9.8mL), dry THF (10mL), and dry n-hexane (40mL) to the constant pressure dropping funnel. Place the three-necked flask in a low-temperature reactor at 0 °C, stir and add dropwise. After the addition is complete, raise the temperature to room temperature and stir for 2 h (monitor the reaction by TLC). At room temperature, add 30 mL of n-hexane, slowly add 4 mL of deionized water dropwise, heat up to 70 °C and reflux and stir for 1 h. Cool, filter off the solid, wash the filter cake with n-hexane, and remove the solvent by rotary evaporation to obtain the product l-butyl-3-methylcyclopentadiene.

[0071] The molar ratio of the endo product to the exo product in the product system was measured by GC to be 74 / 26.

[0072] As described above, the embodiments of the present invention have been described. However, the present invention is not limited to the above embodiments. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. A method for preparing a compound of formula I, characterized in that, the method comprises the following steps: in the presence of trifluoroacetic acid, a compound of formula A reacts to obtain a compound of formula I; wherein, R is selected from a hydrogen atom or a saturated or unsaturated straight-chain or branched-chain alkyl group having 1 to 20 carbon atoms; R' is selected from a saturated or unsaturated straight-chain or branched-chain alkyl group having 1 to 20 carbon atoms; the temperature of the reaction is not higher than 40 °C.

2. The method according to claim 1, characterized in that, the molar ratio of trifluoroacetic acid to the compound of formula A is 0.2:1 to 0.5:

1.

3. The method according to claim 1, characterized in that, the reaction system contains an ether solvent, for example, the ether solvent is selected from any one of diethyl ether, tetrahydrofuran, 1,4-dioxane, and ethylene glycol dimethyl ether.

4. The method according to claim 1, characterized in that, the reaction system further contains water and a C6-C10 alkane solvent.

5. The method according to claim 1, characterized in that, the trifluoroacetic acid is added to the reaction system in a dropwise manner; the temperature of the system during dropwise addition is 5 to 15 °C, preferably 10 °C.

6. The method according to claim 1, characterized in that, the reaction time is not less than 0.5 h.

7. The method according to any one of claims 1 to 6, characterized in that, the compound of formula A is obtained by reacting a compound of formula B with water; preferably, the above reaction system further contains an ether solvent and n-hexane.

8. The method according to any one of claims 1 to 6, characterized in that, the compound of formula B is obtained by reacting a compound of formula C with a Grignard reagent; wherein, X is any one of Cl, Br, and I; preferably, the above reaction is carried out in an ether solvent.

9. The method according to any one of claims 1 to 6, characterized in that, the molar percentage of the endo product of the compound of formula I prepared is not less than 80%.

10. The method according to claim 1, characterized in that, the preparation method of the compound of formula I includes: reacting a compound of formula C with a Grignard reagent to obtain a compound of formula B, reacting the compound of formula B with water to obtain a compound of formula A, and reacting the compound of formula A in the presence of trifluoroacetic acid to obtain a compound of formula I; the synthetic route is as follows: the reaction system contains an ether solvent, preferably the ether solvent is any one of diethyl ether, tetrahydrofuran, 1,4-dioxane, and ethylene glycol dimethyl ether.

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