Synthesis method of alasmigroup intermediate

Abstract

The synthesis method comprises the following steps: carrying out coupling reaction on an initial raw material 1 and a compound 2 under the action of alkali and a noble metal catalyst, carrying out after-treatment, decolorizing, concentrating, dissolving and replacing to obtain a solution of a compound 3, then carrying out pressurized hydrogenation through a catalyst, and filtering out the catalyst to obtain a crude product solution of an intermediate 4, and finally, refining to obtain the ilastrant intermediate 4. According to the invention, an expensive initial material in an original research patent is replaced by 3, 4-dihydro-6-(phenylmethoxy)-1 (2H)-naphthalenone which is easier to obtain and cheaper, so that the production cost is greatly reduced; a breakthrough innovation is made on a synthesis route, tedious and lengthy synthesis steps are shortened from original seven chemical reaction steps to two chemical reaction steps, and post-treatment is simple and controllable; according to the method, the Suzuki coupling reaction catalyzed by noble metal is reduced, and the overall cost is lower on the basis of ensuring the selectivity, the stability and the high yield of the subsequent reaction.

Description

Technical Field

[0001] The invention belongs to the field of medical technology, relates to elastomeric, and in particular to a method for synthesizing an intermediate of elastomeric (RAD1901), a compound for treating metastatic breast cancer (MBC). Background Art

[0002] Elastran (RAD1901) is a selective estrogen receptor downregulator / degrader, or SERD, that crosses the blood-brain barrier and is particularly suitable for the treatment of metastatic breast cancer. RAD1901 has been shown to have good selectivity for the estrogen receptor (ER) and has both estrogen-like and anti-estrogenic effects in different tissues. In many cancers, hormones, such as estrogen, stimulate tumor growth, so the desired therapeutic goal is to block this estrogen-dependent growth while inducing apoptosis of cancer cells. SERDs have the potential to become an emerging class of endocrine therapeutics that can directly induce ER degradation, potentially removing estrogen growth signals in ER-dependent tumors without developing ligand-independent resistance.

[0003] Elacestrant is an anti-breast cancer drug developed by Menarini of Italy and Square Health of the United States. It was approved by the FDA on January 27, 2023. It is the first selective estrogen receptor degrader that can be used for patients with advanced or metastatic breast cancer. The structural formula of the intermediate of Elacestrant is shown below:

[0004]

[0005] Fangyuan Health Company disclosed the following reaction route in patent WO 2020167855A1:

[0006] This method is an original research route, and the reaction route is as follows:

[0007]

[0008] Compound 1 (7-benzyloxy-3-bromo-1,2-dihydronaphthalene) and bipyralidinol diboron are reacted in the presence of a palladium catalyst to obtain an active intermediate 2, which is coupled with compound 3 (N-acetyl-2-bromo-5-methoxyaniline) to obtain compound intermediate 4 (N-[2-[3,4-dihydro-6-benzyloxy]-2-naphthyl]-5-methoxyphenyl]acetamide), which is then reduced by pressure hydrogenation under Pd(OH)2 / C to obtain intermediate 5 (N-[5-methoxy-2-(1,2,3,4-tetrahydro-6-hydroxy-2-naphthyl)phenyl]acetamide), which is then hydrolyzed to obtain an important intermediate 6 of elastomeric (6-(2-amino-4-methoxyphenyl)-5,6,7,8-tetrahydro-2-naphthol).

[0009] Among them, compound 1 is obtained by bromination reaction of starting material A (6-benzyloxy-3,4-dihydro-2H-naphthalen-1-one), and then reacted with sodium borohydride to obtain reduced compound C, and finally eliminated with p-toluenesulfonic acid to obtain dehydration reaction (the reaction route is shown below).

[0010]

[0011] The above method for synthesizing intermediate 6 has lengthy reaction steps and low yield. During the synthesis process, the precious metal palladium catalyst is used multiple times, resulting in a high cost for synthesizing the final product.

[0012] Patent CN116969848A discloses a method for preparing an intermediate of elastomeric drug for treating advanced breast cancer:

[0013] Step 1, 6-hydroxy-3,4-dihydro-1H-2-naphthalenone is first subjected to hydroxyl silylation protection to obtain intermediate 2, and then subjected to CC coupling docking reaction with 3 (1-iodo-4-methoxy-2-nitrobenzene), and finally deprotected to obtain intermediate 2-(4-methoxy-2-nitrophenyl)-1,2,3,4-tetrahydronaphthalene-2,6-diol;

[0014] Step 2: The product of step 1 is subjected to dehydroxylation reaction to obtain the intermediate 6-(4-methoxy-2-nitrophenyl)-5,6,7,8-tetrahydronaphthalen-2-ol;

[0015] Step 3: The product of step 2 is subjected to nitro reduction reaction to obtain 6-(2-amino-4-methylphenyl)-5,6,7,8-tetrahydronaphthalene-2-ol. The reaction scheme is as follows:

[0016]

[0017] However, in the process route of the elastomeric intermediate described in the invention, the initial raw materials are expensive, there are many reaction by-products and the yield is low. Summary of the invention

[0018] In order to solve the defects of the existing process that the overall steps are cumbersome and lengthy, the yield is low and the cost is high, the present invention provides a method for synthesizing an elastomeric intermediate. The raw materials of the present invention are easier to obtain, the production cost is greatly reduced, the synthesis steps are shortened, the post-treatment is simple and controllable, and the Suzuki coupling reaction catalyzed by precious metals is reduced. On the basis of ensuring the selectivity, stability and high yield of subsequent reactions, the overall cost is lower.

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

[0020] The present invention provides a method for synthesizing an elastomeric intermediate, the method comprising the following steps:

[0021] 1) The initial raw material 1 and the compound 2 undergo a coupling reaction under the action of a base and / or a noble metal catalyst, and the solution of the compound 3 is obtained by post-treatment through decolorization, concentration, and dissolution and replacement;

[0022] 2) The solution of compound 3 obtained in step 1) is subjected to pressure hydrogenation with a catalyst, and the catalyst is filtered off to obtain a crude solution of intermediate 4, which is then purified to obtain elastostat intermediate 4;

[0023] Wherein, the structural formula of the initial raw material 1 is as follows:

[0024] The structural formula of compound 2 is shown below:

[0025] The structural formula of compound 3 is shown below:

[0026] The structural formula of elastostat intermediate 4 is shown below:

[0027] In compound 2, X is F, Cl, Br or I.

[0028] Based on an in-depth study of the original research patent (patent WO 2020167855A1), the present invention replaces the expensive initial material (7-benzyloxy-3-bromo-1,2-dihydronaphthalene) in the original research patent with the more easily available and inexpensive 3,4-dihydro-6-(phenylmethoxy)-1(2H)-naphthalenone (the initial synthetic substrate of the main raw material of the original research WO 2020167855A1), which greatly reduces the production cost; at the same time, a breakthrough innovation is made in the synthesis route, which greatly shortens the cumbersome and lengthy synthesis steps in the original process from the original 7 steps of chemical reactions to 2 steps, and the post-treatment is relatively simple and controllable; in the synthesis steps of the method, the Suzuki coupling reaction catalyzed by precious metals is reduced, and the overall cost is lower while ensuring the selectivity, stability and high yield of the subsequent reactions.

[0029] The synthetic route of the present invention is as follows:

[0030]

[0031] As a preferred embodiment of the present invention, in step 1), the base includes potassium carbonate, cesium carbonate, potassium bicarbonate, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium tert-butoxide, sodium hydride, lithium diisopropylamide, lithium bistrimethylsilylamide or potassium bistrimethylsilylamide.

[0032] As a preferred embodiment of the present invention, in step 2), the catalyst includes Raney nickel, ruthenium aluminum catalyst, ruthenium carbon, palladium carbon or palladium hydroxide carbon.

[0033] As a preferred embodiment of the present invention, in step 1) and step 2), the organic solvent used includes ethylene glycol dimethyl ether, acetonitrile, chloroform, dichloromethane, methyl tert-butyl ether, methanol, ethanol, tetrahydrofuran, 2-methyltetrahydrofuran or dimethyl sulfoxide.

[0034] As a preferred embodiment of the present invention, when X is F, when compound 2 undergoes coupling reaction, the reaction temperature of the first stage is controlled at -30°C-0°C, and the reaction temperature of the second stage is controlled at 50°C-70°C.

[0035] As a preferred embodiment of the present invention, when X is Cl, Br or I, the temperature at which the coupling reaction of compound 2 occurs is 50°C-90°C.

[0036] As a preferred embodiment of the present invention, in step 1), when X is Cl, Br or I, the ligand used in the coupling reaction includes triphenylphosphine, tricyclohexylphosphine, tri-tert-butylphosphine tetrafluoroborate, 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl or 2,2'-bipyridine.

[0037] As a preferred embodiment of the present invention, in step 2), the reaction temperature is 20°C-70°C.

[0038] As a preferred embodiment of the present invention, in step 2), the pressure of hydrogen is 1 atm-50 atm.

[0039] Compared with the prior art, the present invention has the following beneficial effects:

[0040] 1) Compared with the expensive starting material 7-benzyloxy-3-bromo-1,2-dihydronaphthalene, the raw material of the present invention is easier to obtain and cheaper, which greatly reduces the production cost.

[0041] 2) Compared with the complicated and lengthy synthesis steps in the original process, the present invention shortens the reaction steps and the post-processing is relatively simple and controllable.

[0042] 3) In the synthesis steps of the present invention, the Suzuki coupling reaction catalyzed by precious metals is reduced, and the overall cost is lower while ensuring the selectivity, stability and high yield (above 85%) of the subsequent reaction.

[0043] 4) The synthesis route of the present invention is simple, the raw material cost is low, it is easy to obtain, the post-treatment is simple and controllable, and the yield is high. BRIEF DESCRIPTION OF THE DRAWINGS

[0044] Figure 1 This is the TGA detection spectrum of elastostat intermediate 4.

[0045] Figure 2This is the HNMR spectrum of elastomeric intermediate 4.

[0046] Figure 3 It is the HPLC spectrum of elastostat intermediate 4. DETAILED DESCRIPTION

[0047] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0048] The present invention is based on an in-depth study of the original research patent (patent WO 2020167855A1), and replaces the expensive initial material (7-benzyloxy-3-bromo-1,2-dihydronaphthalene) in the original research patent with a more easily accessible and cheap 3,4-dihydro-6-(phenylmethoxy)-1(2H)-naphthalenone (the initial synthetic substrate of the main raw material of the original research WO 2020167855A1).

[0049] The synthetic route of the present invention is as follows:

[0050]

[0051] The initial raw material 1 (3,4-dihydro-6-(phenylmethoxy)-1(2H)-naphthalenone) and compound 2 (X=F,Cl,Br,I) undergo coupling reaction in the presence of a base and a noble metal catalyst (optional). The post-treatment includes decolorization, concentration, and dissolution and replacement to obtain a solution of compound 3, which is then pressurized and hydrogenated over a catalyst again, and the catalyst is filtered off to obtain a crude solution of intermediate 4. Finally, it is refined to obtain elastomeric intermediate 4 (6-(2-amino-4-methoxyphenyl)-5,6,7,8-tetrahydro-2-naphthol).

[0052] In one embodiment of the present invention, when X=F, the reaction temperature of the first stage of the coupling reaction of compound 2 is controlled at -30-0°C, preferably -10-0°C; the reaction temperature of the second stage is controlled at 50-70°C, preferably 60-70°C.

[0053] In one embodiment of the present invention, when X = Cl, Br or I, the reaction temperature of the coupling reaction of compound 2 is controlled at 50-90°C, preferably 70-80°C.

[0054] In one embodiment of the present invention, the base includes potassium carbonate, cesium carbonate, potassium bicarbonate, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium tert-butoxide, sodium hydride, lithium diisopropylamide, lithium bistrimethylsilylamide or potassium bistrimethylsilylamide, and potassium tert-butoxide and sodium tert-butoxide are preferred in the present invention.

[0055] In one embodiment of the present invention, the noble metal catalyst includes tetrakis(triphenylphosphine)palladium, palladium acetate, tris(dibenzylideneacetone)dipalladium, bis(triphenylphosphine palladium dichloride) or bis(tri-tert-butylphosphine)palladium, etc., and palladium acetate is preferred in the present invention.

[0056] In one embodiment of the present invention, the ligand used in the coupling reaction includes triphenylphosphine, tricyclohexylphosphine, tri-tert-butylphosphine tetrafluoroborate, Xantphos (4,5-bis-diphenylphosphine-9,9-dimethylxanthene) or BINAP (2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl, 2,2'-bipyridine, and tri-tert-butylphosphine tetrafluoroborate is preferred in the present invention.

[0057] In one embodiment of the present invention, the catalyst in step 2) is Raney nickel, ruthenium aluminum catalyst, ruthenium carbon, palladium carbon or palladium hydroxide carbon, etc., and the preferred catalyst is palladium carbon.

[0058] In one embodiment of the present invention, the organic solvent used can be: ethylene glycol dimethyl ether, acetonitrile, chloroform, dichloromethane, methyl tert-butyl ether, methanol, ethanol, tetrahydrofuran, 2-methyltetrahydrofuran or dimethyl sulfoxide, etc. In step 1), the preferred solvent of the present invention is ethylene glycol dimethyl ether; in step 2), the preferred solvent of the present invention is tetrahydrofuran and methanol.

[0059] In one embodiment of the present invention, in step 2), the reaction temperature is generally controlled at 20-70°C, preferably 35°C in the first stage of the present invention; and preferably 65°C in the second stage.

[0060] In one embodiment of the present invention, the pressure of hydrogen is generally controlled at 1-50 atm, preferably 10 atm in the first stage of the present invention and preferably 40 atm in the second stage.

[0061] Example 1

[0062] In this embodiment, 4-fluoro-3-nitroanisole is used as a raw material, and the reaction scheme is as follows:

[0063]

[0064] Step 1), add ethylene glycol dimethyl ether (100 mL) to a 500 mL reaction bottle, add sodium hydride (8.81 g, 2.2 eq) in batches at 15-25 ° C; dissolve the initial raw material 1 (25.23 g, 0.10 mol) in ethylene glycol dimethyl ether (100 mL), and slowly add it dropwise to the reaction bottle to react to obtain a highly active reaction substrate, and finally add compound 2 (18.81 g, 1.1 eq) in batches, stir for 1 hour, heat to 70-80 ° C, after the reaction is completed, cool to 0-10 ° C, add ice water dropwise to quench, separate the liquid, decolorize, concentrate, replace tetrahydrofuran as a solvent, and obtain a solution of 6-benzyloxy-2-(4-methoxy-2-nitrophenyl)-3,4-dihydronaphthalene-1(2H)-one. This step is not purified and the yield is not counted.

[0065] Step 2), the obtained 6-benzyloxy-2-(4-methoxy-2-nitrophenyl)-3,4-dihydronaphthalene-1(2H)-one tetrahydrofuran solution was added to a 500mL hydrogenation reactor under nitrogen protection at room temperature, a catalyst palladium carbon (2w / w%, based on the initial raw material 1) was added, and methanol (100mL) was added as the reaction solvent, the pressure reactor was closed, the nitrogen replaced the system three times, the hydrogen replaced the system three times, the hydrogen pressure was increased to 10atm, the temperature was controlled at 35°C, and the reaction was carried out for 5-6h; the temperature was raised to 65°C, the hydrogen pressure was slowly increased to 40atm, and after the reaction was completed, the temperature was lowered to 15-25°C, and the mixture was filtered through a filter padded with diatomaceous earth to remove the catalyst, and the filter cake was rinsed with acetonitrile, drained, and the filtrate was concentrated to dryness under reduced pressure to obtain a crude product of 6-(2-amino-4-methylphenyl)-5,6,7,8-tetrahydronaphthalene-2-ol with a yield of 79%.

[0066] Purification: Add 2-methyltetrahydrofuran to dissolve the crude 6-(2-amino-4-methylphenyl)-5,6,7,8-tetrahydronaphthalene-2-ol, extract and wash with sodium bicarbonate aqueous solution, separate the liquids, and collect the organic phase; wash the organic phase three times with saturated brine, and collect the organic phase; control 40-45° C. to concentrate the organic phase under reduced pressure until it becomes viscous, add methyl tert-butyl ether dropwise, stir and disperse, control 15-20° C., keep stirring for ≥6 hours, filter, and rinse the filter cake with methyl tert-butyl ether; collect the filter cake, maintain 20-30° C. with ethanol-water mixture, stir and slurry the filter cake for ≥2 hours, filter, collect the filter cake, and rinse the filter cake with ethanol-water mixture, and pump to near dryness, dry the filter cake, and obtain the elastomeric intermediate 6-(2-amino-4-methylphenyl)-5,6,7,8-tetrahydronaphthalene-2-ol with a yield of 87%.

[0067] The TGA detection spectrum of elastomeric intermediate 4 is shown in Figure 1 , Analysis of elastostat intermediate 4-TGA spectrum:

[0068] Under inert gas protection, compound 4, 25.00 -60.00℃, sample weight loss 0.152%;

[0069] 60.00-80.00℃, sample weight loss 0.108%;

[0070] 60.00-120.00℃, sample weight loss 0.130%;

[0071] 120.00-800.00℃, the sample loses 99.653% of its weight.

[0072] The HNMR spectrum of elastomeric intermediate 4 is shown in Figure 2 The HPLC spectrum of elastomeric intermediate 4 is shown in Figure 3 .

[0073] Example 2

[0074] In this embodiment, 4-bromo-3-nitroanisole is used as a raw material, and the reaction scheme is as follows:

[0075]

[0076] Step 1) Under nitrogen protection, the initial raw material 1 (25.23 g, 0.10 mol) was dissolved in ethylene glycol dimethyl ether (200 mL), and potassium tert-butoxide (24.69 g, 2.2 eq) was added in batches at 10-20 ° C. After stirring for 1 h, compound 2 (24.36 g, 1.05 eq) was added, palladium acetate (0.23 g, 1.0 w / w%), tri-tert-butylphosphine tetrafluoroborate (0.29 g, 1.0w / w%), the reaction system was evacuated to replace nitrogen, the temperature was raised to 70-80°C, after the reaction was completed, the temperature was lowered to 10-20°C, water was added dropwise to quench, ethyl acetate was added, stirred and allowed to stand for separation, the organic phase was decolorized, concentrated, and tetrahydrofuran was replaced as a solvent. The obtained solution of 6-benzyloxy-2-(4-methoxy-2-nitrophenyl)-3,4-dihydronaphthalen-1(2H)-one was not purified in this step, and the yield was not counted.

[0077] Step 2) The obtained 6-benzyloxy-2-(4-methoxy-2-nitrophenyl)-3,4-dihydronaphthalene-1(2H)-one tetrahydrofuran solution was added to a 500mL hydrogenation reactor under nitrogen protection at room temperature, and a catalyst palladium carbon (2w / w%, based on the initial raw material 1) was added, and the reaction solvent methanol (100mL) was added, and the pressure reactor was closed. The nitrogen replaced the system three times, the hydrogen replaced the system three times, the hydrogen pressure was added to 10atm, the temperature was controlled at 35°C, and the reaction was carried out for 5-6h; the temperature was raised to 65°C, and the hydrogen pressure was slowly increased to 40atm. After the reaction was completed, the temperature was lowered to 15-25°C, and the catalyst was removed by filtering with a filter padded with diatomaceous earth, and the filter cake was rinsed with acetonitrile, and the filtrate was drained and concentrated to dryness under reduced pressure to obtain a crude product of 6-(2-amino-4-methylphenyl)-5,6,7,8-tetrahydronaphthalene-2-ol with a yield of 83%.

[0078] Purification: Add 2-methyltetrahydrofuran to dissolve the crude 6-(2-amino-4-methylphenyl)-5,6,7,8-tetrahydronaphthalene-2-ol, extract and wash with sodium bicarbonate aqueous solution, separate the liquids, and collect the organic phase; wash the organic phase three times with saturated brine, and collect the organic phase; control 40-45° C. to concentrate the organic phase under reduced pressure until it becomes viscous, add methyl tert-butyl ether dropwise, stir and disperse, control 15-20° C., keep stirring for ≥6 hours, filter, and rinse the filter cake with methyl tert-butyl ether; collect the filter cake, maintain 20-30° C. with ethanol-water mixture, stir and slurry the filter cake for ≥2 hours, filter, collect the filter cake, and rinse the filter cake with ethanol-water mixture, and pump to near dryness, dry the filter cake, and obtain the elastomeric intermediate 6-(2-amino-4-methylphenyl)-5,6,7,8-tetrahydronaphthalene-2-ol, with a yield of 90%.

[0079] It can be seen that the synthesis route of the present invention is simple, the raw material cost is low, it is easy to obtain, the post-treatment is simple and controllable, and the yield is high.

[0080] The above is only a preferred embodiment of the present invention, and is not any formal or substantial limitation of the present invention. It should be pointed out that ordinary technicians in this technical field can make several improvements and supplements without departing from the method of the present invention, and these improvements and supplements should also be regarded as the protection scope of the present invention. Any technician familiar with this profession, without departing from the spirit and scope of the present invention, can make some changes, modifications and evolutions of the technical content disclosed above, which are equivalent embodiments of the present invention; at the same time, any changes, modifications and evolutions of any equivalent changes made to the above embodiments based on the essential technology of the present invention are still within the scope of the technical solution of the present invention.

Claims

1. A method for synthesizing an elastomeric intermediate, characterized in that: The synthesis method comprises the following steps: 1) The initial raw material 1 and the compound 2 undergo a coupling reaction under the action of a base and / or a noble metal catalyst, and the solution of the compound 3 is obtained by post-treatment through decolorization, concentration, and dissolution and replacement; 2) The solution of compound 3 obtained in step 1) is subjected to pressure hydrogenation with a catalyst, and the catalyst is filtered off to obtain a crude solution of intermediate 4, which is then purified to obtain elastostat intermediate 4; Wherein, the structural formula of the initial raw material 1 is as follows: The structural formula of compound 2 is shown below: The structural formula of compound 3 is shown below: The structural formula of intermediate 4 is shown below: In compound 2, X is F, Cl, Br or I.

2. The method for synthesizing an elastomeric intermediate according to claim 1, characterized in that: In step 1), the base includes potassium carbonate, cesium carbonate, potassium bicarbonate, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium tert-butoxide, sodium hydride, lithium diisopropylamide, lithium bistrimethylsilylamide or potassium bistrimethylsilylamide.

3. The method for synthesizing an elastomeric intermediate according to claim 1, characterized in that: In step 1), the noble metal catalyst includes tetrakis(triphenylphosphine)palladium, palladium acetate, tris(dibenzylideneacetone)dipalladium, bis(triphenylphosphine)palladium dichloride or bis(tri-tert-butylphosphine)palladium.

4. The method for synthesizing an elastomeric intermediate according to claim 1, characterized in that: In step 2), the catalyst includes Raney nickel, ruthenium aluminum catalyst, ruthenium carbon, palladium carbon or palladium hydroxide carbon.

5. The method for synthesizing an elastomeric intermediate according to claim 1, characterized in that: In step 1) and step 2), the organic solvent used includes ethylene glycol dimethyl ether, acetonitrile, chloroform, dichloromethane, methyl tert-butyl ether, methanol, ethanol, tetrahydrofuran, 2-methyltetrahydrofuran or dimethyl sulfoxide.

6. The method for synthesizing an elastomeric intermediate according to any one of claims 1 to 5, characterized in that: When X is F, when compound 2 undergoes coupling reaction, the reaction temperature of the first stage is controlled at -30°C-0°C, and the reaction temperature of the second stage is controlled at 50°C-70°C.

7. The method for synthesizing an elastomeric intermediate according to any one of claims 1 to 5, characterized in that: When X is Cl, Br or I, the temperature for the coupling reaction of compound 2 is 50°C-90°C.

8. The method for synthesizing an elastomeric intermediate according to claim 7, characterized in that: In step 1), when X is Cl, Br or I, the ligand used in the coupling reaction includes triphenylphosphine, tricyclohexylphosphine, tri-tert-butylphosphine tetrafluoroborate, 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl or 2,2'-bipyridine.

9. The method for synthesizing an elastomeric intermediate according to any one of claims 1 to 5, characterized in that: In step 2), the reaction temperature is 20°C-70°C.

10. The method for synthesizing an elastomeric intermediate according to any one of claims 1 to 5, characterized in that: In step 2), the pressure of hydrogen is 1 atm-50 atm.

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