Preparation method of β-arylamine compounds and analogs thereof

Abstract

The present application provides a method for preparing β-arylamine compounds and analogs thereof, comprising the following steps: mixing a rhodium catalyst, a base, a compound represented by formula (1), a compound represented by formula (2) and a compound represented by formula (3), and reacting them under an inert atmosphere to obtain a compound represented by formula (A). The present application uses the compound represented by formula (1), the compound represented by formula (2) and the compound represented by formula (3) as raw materials, reacts them under the action of a rhodium catalyst and a base in an inert atmosphere, and can prepare the β-arylamine compounds represented by formula (A) and analogs thereof in one step, which greatly shortens the synthesis steps and time, has a simple feeding method, is easy to obtain the reaction raw materials, and has a high yield and high purity.

Description

Technical Field

[0001] The invention relates to the technical field of chemical synthesis, and in particular to a method for preparing beta-arylamine compounds and analogs thereof. Background Art

[0002] β-Arylamine compounds are an important class of chemical products or synthetic intermediates. Their phenylethylamine structure plays an important role in medicine and other fields. For example, Agomelatine shown in formula (I), whose chemical name is N-[2-(7-methoxynaphthalen-1-yl)ethyl]acetamide, is a new type of antidepressant drug, mainly used to treat adult depression, and has a standard β-arylamine compound structure:

[0003] Formula (I).

[0004] The compound shown in formula (A-2) has also been shown to have an antidepressant effect, and it also has a standard β-arylamine compound structure:

[0005] Formula (A-2).

[0006] The prior art discloses a variety of routes for synthesizing β-arylamine compounds, but generally they have the disadvantages of having many and complicated reaction steps and low yield. Summary of the invention

[0007] In view of this, the purpose of the present application is to provide a method for preparing β-arylamine compounds and their analogs. The method provided in the present application can prepare β-arylamine compounds and their analogs in one step, with a short reaction route and a high yield.

[0008] The present application provides a method for preparing β-arylamine compounds and analogs thereof, comprising the following steps:

[0009] A rhodium catalyst, a base, a compound represented by formula (1), a compound represented by formula (2) and a compound represented by formula (3) are mixed and reacted under an inert atmosphere to obtain a compound represented by formula (A);

[0010] Ar-M formula (1); Formula (2); Formula (3);

[0011] Formula (A);

[0012] wherein Ar is selected from an aromatic group optionally substituted by one or more substituents or a heteroaryl group optionally substituted by one or more substituents; M is a boron-containing substituent, and the B atom of the boron-containing substituent is connected to the Ar group;

[0013] X is a halogen;

[0014] R 6 , R 7 , R 8 , R 9 Each is independently selected from one of hydrogen, halogen, alkyl optionally substituted by one or more substituents, alkenyl optionally substituted by one or more substituents, alkynyl optionally substituted by one or more substituents, alkoxy optionally substituted by one or more substituents, cyano, amide optionally substituted by one or more substituents, ester optionally substituted by one or more substituents, keto optionally substituted by one or more substituents, phenyl optionally substituted by one or more substituents, naphthyl optionally substituted by one or more substituents, nitrogen-containing heterocycle optionally substituted by one or more substituents, oxygen-containing heterocycle optionally substituted by one or more substituents, and sulfur-containing heterocycle optionally substituted by one or more substituents;

[0015] The substituent is selected from alkyl, haloalkyl, alkoxy, haloalkoxy, cyano, halogen, alkenyl, haloalkenyl, alkenyloxy, alkylthio, haloalkylthio, alkyl-substituted borate, alkanoate, benzyloxy or aromatic groups.

[0016] In some specific implementations, the R 6 , R 7 , R 8 are each independently selected from hydrogen or alkyl optionally substituted by one or more groups;

[0017] R 9 is selected from phenyl optionally substituted by one or more substituents or keto optionally substituted by one or more substituents;

[0018] The substituent is selected from an alkoxy group or an alkyl group.

[0019] In some specific implementations, the molar ratio of the compound represented by formula (1), the compound represented by formula (2) and the compound represented by formula (3) is 0.2-1:0.8-4.0:0.2-3.0.

[0020] In some specific implementations, the molar ratio of the compound represented by formula (1) to the base is 0.2-1:1-3;

[0021] The molar percentage of the rhodium catalyst in the compound represented by formula (1) is 1% to 100%.

[0022] In some specific implementations, the reaction temperature is 0°C to 200°C, and the reaction time is 20 minutes to 36 hours.

[0023] In some specific implementations, the rhodium catalyst is selected from acetylacetonate bis(ethylene) rhodium (I), dicarbonyl acetylacetonate rhodium (I), (1,5-cyclooctadiene) chlororhodium (I) dimer, bis(1,5-cyclooctadiene)-trifluoromethanesulfonate rhodium, bis(1,5-cyclooctadiene) tetrafluoroborate rhodium, tri(triphenylphosphine) rhodium bromide (I), bis[(1,5-cyclooctadiene)(methoxy)rhodium], (1,5-cyclooctadiene) 2,4-pentanedione rhodium (I), chlorobis(ethylene) rhodium (I) dimer, dimerized hydroxy(1,5-cyclooctadiene) rhodium (I), 1,2-bis[(2S,5S)-2,5-diphenylphosphino]ethane (1,5-cyclooctadiene) tetrafluoroborate rhodium (I), carbonyl bis(triphenylphosphino) rhodium chloride (I) , bis(1,5-cyclooctadiene)rhodium(I) antimony hexafluoride salt, tri(triphenylphosphine)carbonylrhodium(I) hydride, (R)-(-)-tert-butylmethyl(di-tert-butylphosphinomethyl)phosphino(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate or one or more thereof.

[0024] In some specific implementations, the base is selected from lithium trimethylsilanolate, sodium trimethylsilanolate, potassium trimethylsilanolate, lithium tert-butoxide, potassium tert-butoxide, sodium tert-butoxide, lithium methoxide, potassium methoxide, sodium methoxide, lithium carbonate, sodium bicarbonate, sodium carbonate, potassium carbonate, sodium thiosulfate, cesium carbonate, lithium hydroxide, potassium hydroxide, sodium hydroxide, calcium hydroxide, magnesium hydroxide, barium hydroxide, sodium sulfate, potassium dihydrogen phosphate, potassium sulfate, potassium trihydrogen phosphate, calcium hydrogen phosphate, potassium tetrahydrogen phosphate, calcium dihydrogen phosphate, calcium tetrahydrogen phosphate, calcium dihydrogen phosphate, sodium phosphate, sodium trihydrogen phosphate, sodium dihydrogen phosphate, sodium tetrahydrogen phosphate, magnesium dihydrogen phosphate, magnesium phosphate, magnesium trihydrogen phosphate, aluminum dihydrogen phosphate, magnesium tetrahydrogen phosphate, aluminum trihydrogen phosphate, copper phosphate, aluminum tetrahydrogen phosphate, copper dihydrogen phosphate, copper trihydrogen phosphate and copper tetrahydrogen phosphate.

[0025] In some specific implementations, the solvent used in the reaction is selected from one or more of water, deuterated water, ethanol, methanol, isopropanol, n-hexane, n-pentane, cyclopentane, dioxane, tetrahydrofuran, 2-methyltetrahydrofuran, acetonitrile, dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, methyl tert-butyl ether, ethyl ether, acetone, benzene, deuterated benzene, toluene, deuterated toluene, p-xylene, o-xylene, m-xylene, ethylbenzene, chlorobenzene, dichloromethane, deuterated dichloromethane, chloroform, deuterated chloroform, tetrahydrofuran and 1,4-dioxane.

[0026] In some specific implementations, the compound represented by formula (1) is selected from one or more of aryl boronic acid, (4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl) aryl compound, aryl potassium trifluoroborate, aryl boronic acid neopentane glycol ester, and 2-aryl-1,3,2-diphenylphenol borane.

[0027] In some specific implementations, the compound represented by formula (2) is selected from vinyl bromide.

[0028] The present application uses the compound represented by formula (1), the compound represented by formula (2) and the compound represented by formula (3) as raw materials, reacts in an inert atmosphere under the action of a rhodium catalyst and a base, and can prepare β-arylamine compounds represented by formula (A) and their analogs in one step, which greatly shortens the synthesis steps and time, has a simple feeding method, is easy to obtain reaction raw materials, and has a high yield and high purity. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 The hydrogen spectrum of the β-arylamine compound provided in Example 1 of the present application;

[0030] Figure 2 The carbon spectrum of the β-arylamine compound provided in Example 1 of the present application;

[0031] Figure 3 The hydrogen spectrum of the β-arylamine compound provided in Example 2 of the present application;

[0032] Figure 4 The carbon spectrum of the β-arylamine compound provided in Example 2 of the present application;

[0033] Figure 5 The hydrogen spectrum of the β-arylamine compound provided in Example 3 of the present application;

[0034] Figure 6 The carbon spectrum of the β-arylamine compound provided in Example 3 of the present application;

[0035] Figure 7 The hydrogen spectrum of the β-arylamine compound provided in Example 4 of the present application;

[0036] Figure 8 The carbon spectrum of the β-arylamine compound provided in Example 4 of the present application;

[0037] Fig. 9 The hydrogen spectrum of the β-arylamine compound provided in Example 5 of the present application;

[0038] Fig.10 The carbon spectrum of the β-arylamine compound provided in Example 5 of the present application;

[0039] Fig.11 The hydrogen spectrum of the β-arylamine compound provided in Example 6 of the present application;

[0040] Fig.12 This is the carbon spectrum of the β-arylamine compounds provided in Example 6 of the present application. DETAILED DESCRIPTION

[0041] It should be understood that the expression "one or more of..." includes each of the items recited after the expression individually and in various different combinations of two or more of the recited items, unless otherwise understood from the context and usage. The expression "and / or" in combination with three or more recited items should be understood to have the same meaning, unless otherwise understood from the context.

[0042] The use of the terms "comprising", "having" or "containing", including their grammatical synonyms, should generally be understood as open and non-restrictive, for example not excluding other unrecited elements or steps, unless otherwise specifically stated or otherwise understood from the context.

[0043] It should be understood that the order of steps or the order in which certain actions are performed is not important as long as the present invention remains operable. In addition, two or more steps or actions may be performed simultaneously.

[0044] The use of any and all examples or exemplary language, such as "for example" or "including", herein is intended only to better illustrate the invention and does not limit the scope of the invention unless otherwise claimed. No language in this specification should be construed as indicating that any non-claimed element is essential to the practice of the invention.

[0045] In addition, the numerical ranges and parameters used to define the present invention are approximate values, and the relevant values ​​in the specific embodiments have been presented as accurately as possible. However, any numerical value inherently inevitably contains standard deviations due to individual test methods. Therefore, unless otherwise expressly stated, it should be understood that all ranges, quantities, values ​​and percentages used in this disclosure are modified by "about". Here, "about" generally means that the actual value is within plus or minus 10%, 5%, 1% or 0.5% of a specific value or range.

[0046] The term "halogen" refers to fluorine, chlorine, bromine and iodine;

[0047] The term "alkyl" represents a saturated straight or branched hydrocarbon group having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylethyl, 1-ethylpropyl, hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl and 1-ethyl-2-methylpropyl;

[0048] The term "alkenyl" represents an unsaturated straight-chain or branched hydrocarbon radical having 2 or 3 to 6 carbon atoms and having a double bond at any desired position, for example, C2-C6-alkenyl such as ethenyl, 1-propenyl, 2-propenyl, 1-methylethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-1-butenyl, 2-methyl-1-butenyl, 3- methyl-1-butenyl, 1-methyl-2-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl, 3-methyl-3-butenyl, 1,1-dimethyl-2-propenyl, 1,2-dimethyl-1-propenyl, 1,2-dimethyl-2-propenyl, 1-ethyl-1-propenyl, 1-ethyl-2-propenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-1-pentenyl, 2 -methyl-1-pentenyl, 3-methyl-1-pentenyl, 4-methyl-1-pentenyl, 1-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-methyl-2-pentenyl, 4-methyl-2-pentenyl, 1-methyl-3-pentenyl, 2-methyl-3-pentenyl, 3-methyl-3-pentenyl, 4-methyl-3-pentenyl, 1-methyl-4-pentenyl, 2-methyl-4-pentenyl, 3-methyl-4-pentenyl, 4-methyl-4-pentenyl, 1,1-dimethyl-2-butenyl, 1,1- dimethyl-3-butenyl, 1,2-dimethyl-1-butenyl, 1,2-dimethyl-2-butenyl, 1,2-dimethyl-3-butenyl, 1,3-dimethyl-1-butenyl, 1,3-dimethyl-2-butenyl, 1,3-dimethyl-3-butenyl, 2,2-dimethyl-3-butenyl, 2,3-dimethyl-1-butenyl, 2,3-dimethyl-2-butenyl, 2,3-dimethyl-3-butenyl, 3,3-dimethyl-1-butenyl, 3,3- dimethyl-2-butenyl, 1-ethyl-1-butenyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 2-ethyl-1-butenyl, 2-ethyl-2-butenyl, 2-ethyl-3-butenyl, 1,1,2-trimethyl-2-propenyl, 1-ethyl-1-methyl-2-propenyl, 1-ethyl-2-methyl-1-propenyl or 1-ethyl-2-methyl-2-propenyl;

[0049] The term "alkynyl" represents a straight-chain or branched hydrocarbon radical having 2 to 6 carbon atoms and having a triple bond at any desired position, such as ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-methyl- 2-Butynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 3-methyl-1-butynyl, 1,1-dimethyl-2-propynyl, 1-ethyl-2-propynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl, 1-methyl-4-pentynyl, 2-methyl-3-pentynyl, 2-methyl-4-pentynyl, 3-methyl-1- pentynyl, 3-methyl-4-pentynyl, 4-methyl-1-pentynyl, 4-methyl-2-pentynyl, 1,1-dimethyl-2-butynyl, 1,1-dimethyl-3-butynyl, 1,2-dimethyl-3-butynyl, 2,2-dimethyl-3-butynyl, 3,3-dimethyl-1-butynyl, 1-ethyl-2-butynyl, 1-ethyl-3-butynyl, 2-ethyl-3-butynyl and 1-ethyl-1-methyl-2-propynyl;

[0050] The term "alkoxy" represents a straight-chain or branched alkyl group (as described above) having 1 to 6 carbon atoms, which is bonded to the main structure via -O-;

[0051] The term "amide" represents a straight-chain or branched alkyl group having 1 to 6 carbon atoms (as described above), which is bonded to the main structure via a -NH-CO- structure;

[0052] The term "ester group" represents a straight-chain or branched alkyl group having 1 to 6 carbon atoms (as described above), which is bonded to the main structure via a -COO- structure;

[0053] The term "keto" represents a straight-chain or branched alkyl group having 1 to 6 carbon atoms (as described above), which is bonded to the main structure via a -CO- structure;

[0054] The term "aromatic group" represents an unsaturated aromatic hydrocarbon group having 6 to 20 carbon atoms, such as phenyl, o-tolyl, 1-naphthyl (or α-naphthyl) or 2-naphthyl, etc.;

[0055] The term "heteroaryl" represents an aromatic group as described above, wherein at least one carbon atom is replaced by a heteroatom, such as N, O or S;

[0056] The term "nitrogen-containing heterocyclic group" represents a nitrogen-containing heterocyclic group, which is bonded to the main structure through -N-, and in addition to C and N, may also contain the group consisting of oxygen and sulfur as ring members, for example, it may be a 5-membered nitrogen-containing heterocyclic group containing one to four nitrogen atoms or one to three nitrogen atoms and one sulfur or oxygen atom; the nitrogen-containing heterocyclic group may be a nitrogen-containing six-membered heterocyclic group, including carbon atoms and one to five nitrogen atoms, and in addition, may contain a sulfur atom or an oxygen atom as a ring member, etc.;

[0057] The term "oxygen-containing heterocyclic group" represents a heterocyclic group containing oxygen, which is bonded to the main structure through -O-, and in addition to C and O, may also contain the group consisting of nitrogen and sulfur as ring members, for example, it may be a 5-membered oxygen-containing heterocyclic group containing one to four oxygen atoms or one to three oxygen atoms and one sulfur or nitrogen atom; the oxygen-containing heterocyclic group may be an oxygen-containing six-membered heterocyclic group, including carbon atoms and one to five oxygen atoms, and in addition, may also contain a sulfur atom or a nitrogen atom as a ring member, etc.;

[0058] The term "sulfur-containing heterocyclic group" represents a sulfur-containing heterocyclic group, which is bonded to the main structure through -S-, and in addition to C and S, may also contain the group consisting of oxygen and nitrogen as ring members, for example, it may be a 5-membered nitrogen-containing heterocyclic group containing one to four sulfur atoms or one to three sulfur atoms and one nitrogen or oxygen atom; the sulfur-containing heterocyclic group may be a sulfur-containing six-membered heterocyclic group, including carbon atoms and one to five sulfur atoms, and in addition, may contain one sulfur atom or nitrogen atom as a ring member, etc.;

[0059] The term "borate" refers to a 3 -) bonded to the main structure.

[0060] The present application provides a method for preparing β-arylamine compounds and analogs thereof, comprising the following steps:

[0061] A rhodium catalyst, a base, a compound represented by formula (1), a compound represented by formula (2) and a compound represented by formula (3) are mixed and reacted under an inert atmosphere to obtain a compound represented by formula (A);

[0062] Ar-M formula (1); Formula (2); Formula (3);

[0063] Formula (A);

[0064] wherein Ar is selected from an aryl group optionally substituted by one or more substituents or a heteroaryl group optionally substituted by one or more substituents; M is a boron-containing substituent, and the B atom of the boron-containing substituent is connected to the Ar group;

[0065] X is a halogen;

[0066] R 6 , R 7 , R 8 , R 9 Each is independently selected from one of hydrogen, halogen, alkyl optionally substituted by one or more substituents, alkenyl optionally substituted by one or more substituents, alkynyl optionally substituted by one or more substituents, alkoxy optionally substituted by one or more substituents, cyano, amide optionally substituted by one or more substituents, ester optionally substituted by one or more substituents, keto optionally substituted by one or more substituents, phenyl optionally substituted by one or more substituents, naphthyl optionally substituted by one or more substituents, nitrogen-containing heterocycle optionally substituted by one or more substituents, oxygen-containing heterocycle optionally substituted by one or more substituents, and sulfur-containing heterocycle optionally substituted by one or more substituents;

[0067] The substituent is selected from alkyl, haloalkyl, alkoxy, haloalkoxy, cyano, halogen, alkenyl, haloalkenyl, alkenyloxy, alkylthio, haloalkylthio, alkyl-substituted borate, alkanoate, benzyloxy or aromatic groups.

[0068] The present application uses the compound represented by formula (1), the compound represented by formula (2) and the compound represented by formula (3) as raw materials, reacts in an inert atmosphere under the action of a rhodium catalyst and a base, and can prepare β-arylamine compounds represented by formula (A) and their analogs in one step, which greatly shortens the synthesis steps and time, has a simple feeding method, is easy to obtain reaction raw materials, and has a high yield and high purity.

[0069] This application uses the compound represented by formula (1) as the raw material:

[0070] Ar-M formula (1);

[0071] Wherein, M is a boron-containing substituent, and the B atom of the boron-containing substituent is connected to the Ar group, for example, it can be a boronic acid residue that has lost at least one hydroxyl group, a boric acid ester residue that has lost at least one hydroxyl group, or a boric acid salt residue that has lost at least one hydroxyl group, and optionally, the boric acid ester or boric acid salt can be substituted by a halogen. In the present application, the M group is used as a leaving group, and as long as the B atom is connected to the Ar group, it can be removed under the action of a catalyst and a base, so that the Ar group reacts with the double bond of the compound shown in formula (2). Therefore, the present application has no special restrictions on the boron-containing group.

[0072] In formula (1), Ar is selected from an aromatic group optionally substituted by one or more substituents or a heteroaryl group optionally substituted by one or more substituents, preferably selected from a phenyl group optionally substituted by one or more substituents, a biphenyl group optionally substituted by one or more substituents, a naphthyl group optionally substituted by one or more substituents, an indolyl group optionally substituted by one or more substituents, a furanyl group optionally substituted by one or more substituents or a pyridyl group optionally substituted by one or more substituents, more preferably a biphenyl group optionally substituted by one or more substituents, a naphthyl group optionally substituted by one or more substituents or an indolyl group optionally substituted by one or more substituents.

[0073] In some specific implementations, examples of the substituents are as follows: Examples of alkyl groups include methyl, ethyl, propyl, butyl, pentyl, hexyl, isomers thereof, and cycloalkyl groups. Examples of alkenyl groups include vinyl, propenyl, butenyl, pentenyl, hexenyl, isomers thereof, and cycloalkenyl groups. Examples of alkynyl groups include ethynyl, propynyl, butynyl, pentynyl, hexynyl, and isomers thereof. Alkoxy refers to a group formed by the above-mentioned alkyl group connected to an oxygen atom, such as methoxy, ethoxy, etc. Haloalkyl refers to a group formed by the above-mentioned alkyl group being substituted by one or more halogens, such as trifluoromethyl. Haloalkoxy refers to a group formed by the above-mentioned haloalkyl group being connected to an oxygen atom, such as trifluoromethoxy, etc. Halogen refers to fluorine, chlorine, bromine, and iodine. Haloalkenyl refers to a group formed by the above-mentioned alkenyl group being substituted by one or more halogens, such as difluorovinyl. Alkenyloxy refers to a group formed by the above-mentioned alkenyl group being connected to an oxygen atom, such as vinyloxy, propenyloxy, etc. Examples of alkylthio groups include methylthio, ethylthio, propylthio, butylthio, pentylthio, hexylthio and isomers thereof and cycloalkylthio. Halogenated alkylthio refers to a group in which the above alkylthio is substituted by one or more halogens, such as trifluoromethylthio. Examples of alkyl-substituted borate groups include 3,4-tetramethyldioxaborolanyl, etc. Alkylcarboxyl refers to a group in which the above alkyl is substituted by one or more carboxyl groups. Examples of alkylalkanoate groups include methyl formate, etc. Examples of aromatic groups include naphthalene, biphenyl, etc.

[0074] In some specific implementations, the substituents may be 1, 2 or 3, and the substituents are preferably alkyl, halogenated alkyl, halogen, alkenyl and the like.

[0075] In some specific implementations, the compound represented by formula (1) includes but is not limited to: aryl boronic acid, (4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl) aryl compound, aryl trifluoroborate potassium, aryl boronic acid neopentane glycol ester, 2-aryl-1,3,2-benzenediol borane, such as phenyl boronic acid, (4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl) phenyl compound, phenyl trifluoroborate potassium, 4-biphenyl trifluoroborate potassium, phenyl boronic acid neopentane glycol ester, 2-phenyl-1,3,2-benzenediol borane, 2-naphthalene boronic acid pinacol ester, N-methylindole-5-boric acid, etc.

[0076] This application uses the halogenated olefin represented by formula (2) as the raw material:

[0077] Formula (2);

[0078] Wherein, X is a halogen, preferably bromine.

[0079] R 6 , R 7 , R 8 Each independently selected from hydrogen, halogen, alkyl optionally substituted by one or more substituents, alkenyl optionally substituted by one or more substituents, alkynyl optionally substituted by one or more substituents, alkoxy optionally substituted by one or more substituents, cyano, amide optionally substituted by one or more substituents, ester optionally substituted by one or more substituents, keto optionally substituted by one or more substituents, phenyl optionally substituted by one or more substituents, naphthyl optionally substituted by one or more substituents, nitrogen-containing heterocycle optionally substituted by one or more substituents, oxygen-containing heterocycle optionally substituted by one or more substituents, sulfur-containing heterocycle optionally substituted by one or more substituents, preferably independently selected from hydrogen or optionally substituted by one or more substituents alkyl. Each substituent has the definition as described above, and the application is not repeated here, preferably alkyl or alkoxy.

[0080] In some specific implementations, the compound represented by formula (2) includes but is not limited to: vinyl bromide, vinyl chloride, vinyl iodide and vinyl fluoride.

[0081] The present application uses the compound shown in formula (3) as a raw material, and its structural formula is as follows:

[0082] .

[0083] R 9Selected from hydrogen, halogen, alkyl optionally substituted by one or more substituents, alkenyl optionally substituted by one or more substituents, alkynyl optionally substituted by one or more substituents, alkoxy optionally substituted by one or more substituents, cyano, amide optionally substituted by one or more substituents, ester optionally substituted by one or more substituents, keto optionally substituted by one or more substituents, phenyl optionally substituted by one or more substituents, naphthyl optionally substituted by one or more substituents, nitrogen-containing heterocycle optionally substituted by one or more substituents, oxygen-containing heterocycle optionally substituted by one or more substituents, sulfur-containing heterocycle optionally substituted by one or more substituents, preferably selected from phenyl optionally substituted by one or more substituents or keto optionally substituted by one or more substituents. Each substituent has the definition as described above, and the application is not repeated here, preferably alkyl or alkoxy.

[0084] In some specific implementations, the compound represented by formula (3) includes but is not limited to: acetamide, p-methoxyaniline, 5-aminofuran-2-carboxylic acid methyl ester, 4-(furan-2-yl)aniline, 3-aminofuran-2-carboxylic acid methyl ester, and 2-naphthylamine.

[0085] In the preparation method provided by the present application, the solvent used in the reaction includes but is not limited to water, deuterated water, ethanol, methanol, isopropanol, n-hexane, n-pentane, cyclopentane, dioxane, tetrahydrofuran, 2-methyltetrahydrofuran, acetonitrile, dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, methyl tert-butyl ether, ethyl ether, acetone, benzene, deuterated benzene, toluene, deuterated toluene, p-xylene, o-xylene, m-xylene, ethylbenzene, chlorobenzene, dichloromethane, deuterated dichloromethane, chloroform, deuterated chloroform, tetrahydrofuran and one or more of 1,4-dioxane, preferably p-xylene, tetrahydrofuran, 1,4-dioxane or dimethyl sulfoxide.

[0086] The present application uses a rhodium-containing compound as a catalyst. In some specific implementations, the rhodium catalyst includes but is not limited to acetylacetonate bis(ethylene) rhodium (I), dicarbonyl acetylacetonate rhodium (I), (1,5-cyclooctadiene) chlororhodium (I) dimer, bis(1,5-cyclooctadiene)-trifluoromethanesulfonate rhodium, bis(1,5-cyclooctadiene) tetrafluoroborate rhodium, tri(triphenylphosphine) rhodium bromide (I), bis[(1,5-cyclooctadiene)(methoxy)rhodium], (1,5-cyclooctadiene) 2,4-pentanedione rhodium (I), chlorobis(ethylene) rhodium (I) dimer, dipolymerized hydroxy(1,5-cyclooctadiene) rhodium (I), 1,2-bis[(2S,5S)-2,5-diphenylphosphino]ethane (1,5-cyclooctadiene) tetrafluoroborate rhodium (I), carbonyl bis(triphenylphosphino) rhodium chloride (I) , bis(1,5-cyclooctadiene)rhodium(I) hexafluoride antimony salt, tri(triphenylphosphine)carbonyl rhodium(I) hydride, (R)-(-)-tert-butylmethyl(di-tert-butylphosphinomethyl)phosphino(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate or more, preferably bis(1,5-cyclooctadiene)rhodium tetrafluoroborate, chlorobis(ethylene)rhodium(I) dimer, acetylacetonatobis(ethylene)rhodium(I) or tri(triphenylphosphine)rhodium(I) bromide.

[0087] The preparation method provided in the present application also includes a base, and the base includes but is not limited to lithium trimethylsilanolate, sodium trimethylsilanolate, potassium trimethylsilanolate, lithium tert-butoxide, potassium tert-butoxide, sodium tert-butoxide, lithium methoxide, potassium methoxide, sodium methoxide, lithium carbonate, sodium bicarbonate, sodium carbonate, potassium carbonate, sodium thiosulfate, cesium carbonate, lithium hydroxide, potassium hydroxide, sodium hydroxide, calcium hydroxide, magnesium hydroxide, barium hydroxide, sodium sulfate, potassium dihydrogen phosphate, potassium sulfate, potassium trihydrogen phosphate, calcium hydrogen phosphate, potassium tetrahydrogen phosphate, calcium tetrahydrogen phosphate, calcium dihydrogen phosphate, sodium phosphate, sodium trihydrogen phosphate, sodium dihydrogen phosphate, sodium tetrahydrogen phosphate, magnesium dihydrogen phosphate, magnesium phosphate, magnesium trihydrogen phosphate, aluminum dihydrogen phosphate, magnesium tetrahydrogen phosphate, aluminum trihydrogen phosphate, copper phosphate, aluminum tetrahydrogen phosphate, copper dihydrogen phosphate, copper trihydrogen phosphate and copper tetrahydrogen phosphate, preferably sodium carbonate, lithium tert-butoxide or cesium carbonate.

[0088] In the present application, the molar ratio of the compound represented by formula (1), the compound represented by formula (2) and the compound represented by formula (3) is 0.2~1:0.8~4.0:0.2~3.0, preferably 0.5~0.8:1~3.5:1~3. In some specific implementations, the molar ratio of the compound represented by formula (1) to the base is 0.2~1:1~3, preferably 0.5~0.8:1.5~3. In some specific implementations, the molar percentage of the rhodium catalyst in the compound represented by formula (1) is 1%~100%, preferably 2%~50%, and more preferably 3%~15%. In some specific implementations, the molar volume ratio of the compound represented by formula (1) to the reaction medium is 0.2mmol~1mmol:0.5mL~10mL, preferably 0.3mmol:2mL~6mL.

[0089] In the present application, the compound represented by formula (1), the compound represented by formula (2), the compound represented by formula (3), a rhodium catalyst and a base are uniformly mixed in a reaction medium and reacted to obtain a β-arylamine compound represented by formula (A) and its analogs. The reaction process is as follows:

[0090]

[0091] In some specific implementations, the reaction temperature is 0°C to 200°C, preferably 40°C to 150°C, more preferably 60°C to 120°C, more preferably 70°C to 100°C; the reaction time is 20min to 36h, preferably 5h to 30h, more preferably 6h to 24h. In some specific implementations, the reaction is preferably carried out in an oil bath.

[0092] After the reaction is completed, the reaction medium, ie, the solvent, is removed, and the obtained residue is eluted by silica gel column chromatography to obtain the β-arylamine compound represented by formula (A) and its analogs.

[0093] The present application uses the compound represented by formula (1), the compound represented by formula (2) and the compound represented by formula (3) as raw materials, reacts in an inert atmosphere under the action of a rhodium catalyst and a base, and can prepare β-arylamine compounds represented by formula (A) and their analogs in one step, which greatly shortens the synthesis steps and time, has a simple feeding method, is easy to obtain reaction raw materials, and has a high yield and high purity.

[0094] The synthesis method of the β-arylamine compounds and their analogs provided by the present application is further described below in conjunction with the examples. Example 1

[0095] Under the protection of an inert atmosphere, 0.3 mmol of potassium 4-biphenyl trifluoroborate, 1 mmol of vinyl bromide, 1.1 mmol of p-methoxyaniline, 0.03 mmol of tris(triphenylphosphine)rhodium bromide (I) and 1.5 mmol of sodium carbonate were mixed, and 6 mL of p-xylene was added, and the mixture was stirred in an oil bath at 100 °C for 20 h. After the reaction was completed, the solvent was removed, the residue was eluted by silica gel column chromatography, and the product was collected to obtain β-arylamine compounds and their analogs with a purity of 96% and a yield of 60%.

[0096] The β-arylamine compounds and their analogs were subjected to NMR analysis, and the results are shown in Figure 1 and Figure 2 , Figure 1 The hydrogen spectrum of the β-arylamine compounds and their analogs provided in Example 1 of the present application, Figure 2 This is the carbon spectrum of the β-arylamine compounds and their analogs provided in Example 1 of the present application. The NMR data are as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.63-7.56 (m, 2H), 7.58-7.52 (m, 2H), 7.49-7.40 (m, 2H),7.39- 7.30 (m, 1H), 7.30 (d, J = 8.14 Hz, 2H), 6.88 – 6.78 (m, 2H), 6.73-6.63(m, 2H), 3.76 (s, 3H), 3.41 (t, J = 7.03 Hz, 2H), 2.97 (t, J = 7.03 Hz, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 152.4, 141.9, 140.9, 139.4, 138.4, 129.3,128.8, 127.4, 127.2, 127.1, 115.0, 114.7, 55.8, 46.2, 35.2. HRMS (EI) m / z:[(M)+] Calcd for C 21 H 21 NO + 303.1623; Found 303.1619.

[0097] It has the structure of formula (A-1), and its chemical name is N-(2-([1,1'-biphenyl]-4-yl)ethyl)-4-methoxyaniline:

[0098] Formula (A-1). Example 2

[0099] Under the protection of an inert atmosphere, 0.3 mmol of 1-naphthoboric acid pinacol ester, 1 mmol of vinyl bromide, 1.1 mmol of cyclobutylcarboxamide, 0.03 mmol of bis(1,5-cyclooctadiene)-trifluoromethanesulfonic acid rhodium and 1.5 mmol of sodium methoxide were mixed, and 6 mL of dioxane was added, and the mixture was stirred in an oil bath at 100 °C for 20 h. After the reaction was completed, the solvent was removed, the residue was eluted by silica gel column chromatography, and the product was collected to obtain β-arylamine compounds and their analogs with a purity of 93% and a yield of 51%.

[0100] The β-arylamine compounds and their analogs were subjected to NMR analysis, and the results are shown in Figure 3 and Figure 4 , Figure 3 The hydrogen spectrum of the β-arylamine compounds and their analogs provided in Example 2 of the present application, Figure 4 This is the carbon spectrum of the β-arylamine compounds and their analogs provided in Example 2 of the present application. The NMR data are as follows: 1 H NMR (500 MHz, Chloroform-d) δ 8.12 (d, J = 8.48 Hz, 1H), 7.86 (dd, J = 8.06, 1.49 Hz, 1H), 7.75 (d, J = 8.21 Hz, 1H), 7.57-7.50 (m, 1H), 7.52-7.46 (m, 1H), 7.44-7.37(m, 1H), 7.31 (d, J = 6.84 Hz, 1H), 5.50 (s, 1H), 3.72-3.51 (m, 2H), 3.29 (t,J = 7.09 Hz, 2H), 2.91 (p, J = 8.58 Hz, 1H), 2.33-2.18 (m, 2H), 2.16-2.02 (m,2H), 1.99-1.87 (m, 1H), 1.89-1.78 (m, 1H). 13 C NMR (126 MHz, Chloroform-d) δ175.2, 135.2, 133.9, 132.0, 128.8, 127.4, 126.8, 126.2, 125.8, 125.5, 123.8,40.2, 40.0, 32.9, 25.4, 18.1. HRMS (EI) m / z: [(M)+] Calcd for C17 H 19 NO + 253.1467; Found 253.1462.

[0101] It has the structure of formula (A-2), and its chemical name is N-(2-(naphthalen-2-yl)ethyl)cyclobutanecarboxamide:

[0102] Formula (A-2). Example 3

[0103] Under the protection of an inert atmosphere, 0.3 mmol of N-methylindole-5-boric acid, 1 mmol of vinyl bromide, 1.1 mmol of p-methoxyaniline, 0.03 mmol of chlorobis(vinyl)rhodium(I) dimer and 1.5 mmol of cesium carbonate were mixed, and 6 mL of tetrahydrofuran was added, and the mixture was stirred in an oil bath at 100 °C for 20 h. After the reaction was completed, the solvent was removed, the residue was eluted by silica gel column chromatography, and the product was collected to obtain β-arylamine compounds and their analogs with a purity of 91% and a yield of 53%.

[0104] The β-arylamine compounds and their analogs were subjected to NMR analysis, and the results are shown in Figure 5 and Figure 6 , Figure 5 The hydrogen spectrum of the β-arylamine compounds and their analogs provided in Example 3 of the present application, Figure 6 This is the carbon spectrum of the β-arylamine compounds and their analogs provided in Example 3 of the present application. The NMR data are as follows: 1 H NMR (500 MHz, Chloroform-d) δ 7.46 (d, J = 1.57 Hz, 1H), 7.27 (d, J = 8.41 Hz, 1H), 7.09 (dd, J = 8.41, 1.57 Hz, 1H), 7.05 (d, J = 3.09 Hz, 1H), 6.84-6.75 (m, 2H),6.67-6.57 (m, 2H), 6.43 (d, J = 3.09 Hz, 1H), 3.79 (s, 3H), 3.75 (s, 3H),3.39 (t, J = 7.00 Hz, 2H), 3.02 (t, J = 7.00 Hz, 2H). 13C NMR (126 MHz, Chloroform-d) δ 152.4, 141.9, 135.7, 129.85, 129.2, 128.7, 122.6, 120.7,114.9, 109.4, 100.5, 55.8, 47.0, 35.4, 32.9. HRMS (EI) m / z: [(M)+] Calcd forC 18 H 20 N 2 O + 280.1576; Found 280.1574.

[0105] It has the structure of formula (A-3), and its chemical name is 4-methoxy-N-(2-(1-methyl-1H-indol-5-yl)ethyl)aniline:

[0106] Formula (A-3). Example 4

[0107] Under the protection of an inert atmosphere, 0.3 mmol of [1,1'-biphenyl]-4-ylboronic acid, 1 mmol of vinyl bromide, 1.1 mmol of 4-(furan-2-yl)aniline, 0.03 mmol of bis(1,5-cyclooctadiene)rhodium(I) antimony hexafluoride salt and 1.5 mmol of potassium carbonate were mixed, and 6 mL of m-xylene was added, and the mixture was stirred in an oil bath at 100 °C for 20 h. After the reaction was completed, the solvent was removed, the residue was eluted by silica gel column chromatography, and the product was collected to obtain β-arylamine compounds and their analogs with a purity of 97% and a yield of 60%.

[0108] The β-arylamine compounds and their analogs were subjected to NMR analysis, and the results are shown in Figure 7 and Figure 8 , Figure 7 The hydrogen spectrum of the β-arylamine compounds and their analogs provided in Example 4 of the present application, Figure 8 This is the carbon spectrum of the β-arylamine compounds and their analogs provided in Example 4 of the present application. Its NMR data are as follows: 1H NMR (400 MHz,Chloroform-d) δ 7.64 – 7.50 (m, 3H), 7.50 – 7.41 (m, 1H), 7.43 – 7.38 (m,1H), 7.40 – 7.32 (m, 0H), 7.35 – 7.28 (m, 1H), 6.74 – 6.65 (m, 1H), 6.52 –6.39 (m, 1H), 3.48 (t, J = 7.0 Hz, 1H), 2.99 (t, J = 7.0 Hz, 1H). 13 C NMR (101MHz, Chloroform-d) δ 154.7, 147.0, 140.9, 140.8, 139.5, 138.2, 129.3, 128.8,127.4, 127.2, 127.1, 125.3, 121.3, 113.3, 111.5, 102.2, 45.2, 35.0. HRMS (EI)m / z: [(M)+] Calcd for C 24 H 21 NO + 339.1623; Found 339.1620.

[0109] It has the structure of formula (A-4), and its chemical name is N-(2-([1,1'-biphenyl]-4-yl)ethyl)-4-(furan-2-yl)aniline:

[0110] Formula (A-4). Example 5

[0111] Under the protection of an inert atmosphere, 0.3 mmol of [1,1'-biphenyl]-4-ylboronic acid, 1 mmol of vinyl bromide, 1.1 mmol of methyl 3-aminofuran-2-carboxylate, 0.03 mmol of chlorobis(vinyl)rhodium(I) dimer and 1.5 mmol of potassium tert-butoxide were mixed, and 6 mL of n-hexane was added, and the mixture was stirred in an oil bath at 100 °C for 20 h. After the reaction was completed, the solvent was removed, the residue was eluted by silica gel column chromatography, and the product was collected to obtain β-arylamine compounds and their analogs with a purity of 94% and a yield of 52%.

[0112] The β-arylamine compounds and their analogs were subjected to NMR analysis, and the results are shown in Fig. 9 and Fig.10, Fig. 9 The hydrogen spectrum of the β-arylamine compounds and their analogs provided in Example 5 of the present application, Fig.10 This is the carbon spectrum of the β-arylamine compounds and their analogs provided in Example 5 of the present application. The NMR data are as follows: 1 H NMR (400 MHz, Chloroform- d ) δ 7.61 – 7.51 (m, 4H), 7.50 – 7.38 (m, 3H), 7.38 – 7.27 (m,1H), 7.30 – 7.26 (m, 2H), 6.19 (d, J = 2.1 Hz, 1H), 3.84 (s, 3H), 3.46 (t, J =7.2 Hz, 2H), 2.93 (t, J = 7.2 Hz, 2H). 13 C NMR (101 MHz, Chloroform- d ) δ 160.8,146.5, 140.9, 139.6, 137.8, 129.2, 128.8, 128.4, 127.4, 127.2, 127.0, 115.7,102.3, 51.0, 46.7, 36.3. HRMS (EI) m / z: [(M) + ] Calcd for C 20 H 19 NO 3 + 321.1365;Found 321.1361.

[0113] It has the structure of formula (A-5), and its chemical name is methyl 3-((2-([1,1'-biphenyl]-4-yl)ethyl)amino)furan-2-carboxylate:

[0114] Formula (A-5). Example 6

[0115] Under the protection of an inert atmosphere, 0.3 mmol of 1-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole, 1 mmol of vinyl bromide, 1.1 mmol of p-methoxyaniline, 0.03 mmol of tris(triphenylphosphine)rhodium bromide (I) and 1.5 mmol of sodium phosphate were mixed, and 6 mL of acetone was added, and the mixture was stirred in an oil bath at 100 °C for 20 h. After the reaction was completed, the solvent was removed, the residue was eluted by silica gel column chromatography, and the product was collected to obtain β-arylamine compounds and their analogs with a purity of 92% and a yield of 48%.

[0116] The β-arylamine compounds and their analogs were subjected to NMR analysis, and the results are shown in Fig.11 and Fig.12 , Fig.11 The hydrogen spectrum of the β-arylamine compounds and their analogs provided in Example 6 of the present application, Fig.12 This is the carbon spectrum of the β-arylamine compounds and their analogs provided in Example 6 of the present application. The NMR data are as follows: 1 H NMR (500 MHz, Chloroform-d) δ 6.83 – 6.76 (m, 2H), 6.63 – 6.59 (m, 2H), 6.57 (dd, J = 2.7,1.8 Hz, 1H), 6.08 (dd, J = 3.5, 2.7 Hz, 1H), 5.97 (dd, J = 3.5, 1.8 Hz, 1H), 3.75 (s, 3H), 3.54 (s, 3H), 3.35 (t, J = 6.9 Hz, 2H), 2.87 (t, J = 6.9 Hz, 2H). 13 C NMR (126 MHz, Chloroform-d) δ 152.3, 142.1, 130.1, 121.8, 115.0,114.5, 106.9, 106.5, 55.8, 44.0, 33.7, 26.2. HRMS (EI) m / z: [(M)+] Calcd forC 14 H 18 N 2 O + 230.1419; Found 230.1416.

[0117] It has the structure of formula (A-6), and its chemical name is 4-methoxy-N-(2-(1-methyl-1H-pyrrol-2-yl)ethyl)aniline:

[0118] Formula (A-6).

[0119] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A method for preparing β-arylamine compounds and analogs thereof, comprising the following steps: A rhodium catalyst, a base or sodium phosphate, a compound represented by formula (1), a compound represented by formula (2) and a compound represented by formula (3) are mixed and reacted under an inert atmosphere to obtain a compound represented by formula (A); Ar-M formula (1); Formula (2); Formula (3); Formula (A); Wherein, the compound Ar-M represented by formula (1) is selected from one or more of aryl boronic acid, (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) aryl compound and aryl potassium trifluoroborate; the aryl group is an unsaturated aromatic hydrocarbon group having 6 to 20 carbon atoms; X is a halogen; R6, R7, and R8 are each independently selected from hydrogen; R9 is selected from hydrogen, halogen, an alkyl group having 1 to 6 carbon atoms optionally substituted by one or more substituents, an alkoxy group having 1 to 6 carbon atoms optionally substituted by one or more substituents, an ester group having 1 to 6 carbon atoms optionally substituted by one or more substituents, a keto group having 1 to 6 carbon atoms optionally substituted by one or more substituents, a phenyl group optionally substituted by one or more substituents, a naphthyl group optionally substituted by one or more substituents, a nitrogen-containing heterocycle optionally substituted by one or more substituents, an oxygen-containing heterocycle optionally substituted by one or more substituents, The nitrogen-containing heterocyclic group is a 5-membered nitrogen-containing heterocyclic group containing one to four nitrogen atoms or one to three nitrogen atoms and one sulfur or oxygen atom, or a nitrogen-containing six-membered heterocyclic group containing carbon atoms and one to five nitrogen atoms; the oxygen-containing heterocyclic group is a 5-membered oxygen-containing heterocyclic group containing one to four oxygen atoms or one to three oxygen atoms and one sulfur or nitrogen atom, or an oxygen-containing six-membered heterocyclic group including carbon atoms and one to five oxygen atoms; the sulfur-containing heterocyclic group is a 5-membered nitrogen-containing heterocyclic group containing one to four sulfur atoms or one to three sulfur atoms and one nitrogen or oxygen atom, or a sulfur-containing six-membered heterocyclic group including carbon atoms and one to five sulfur atoms; The substituent is selected from an alkyl group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, a haloalkoxy group having 1 to 6 carbon atoms, or a halogen; The rhodium catalyst is selected from one or more of bis(1,5-cyclooctadiene)-trifluoromethanesulfonate rhodium, tri(triphenylphosphine)rhodium(I) bromide, chlorobis(ethylene)rhodium(I) dimer, and bis(1,5-cyclooctadiene)rhodium(I) antimony hexafluoride salt; The base is selected from one or more of lithium trimethylsilanolate, sodium trimethylsilanolate, potassium trimethylsilanolate, lithium tert-butoxide, potassium tert-butoxide, sodium tert-butoxide, lithium methoxide, potassium methoxide, sodium methoxide, lithium carbonate, sodium bicarbonate, sodium carbonate, potassium carbonate, cesium carbonate, lithium hydroxide, potassium hydroxide, sodium hydroxide, calcium hydroxide, magnesium hydroxide, and barium hydroxide.

2. The preparation method according to claim 1, characterized in that: R9 is selected from a phenyl group optionally substituted by one or more substituents or a keto group having 1 to 6 carbon atoms optionally substituted by one or more substituents; The substituent is selected from an alkoxy group having 1 to 6 carbon atoms or an alkyl group having 1 to 6 carbon atoms.

3. The preparation method according to claim 1 or 2, characterized in that: The molar ratio of the compound represented by formula (1), the compound represented by formula (2) and the compound represented by formula (3) is 0.2-1:0.8-4.0:0.2-3.

0.

4. The preparation method according to claim 1 or 2, characterized in that: The molar ratio of the compound represented by formula (1) to the alkali or sodium phosphate is 0.2-1:1-3; The molar percentage of the rhodium catalyst in the compound represented by formula (1) is 1% to 100%.

5. The preparation method according to claim 1 or 2, characterized in that: The reaction temperature is 0°C to 200°C, and the reaction time is 20 minutes to 36 hours.

6. The preparation method according to claim 1 or 2, characterized in that: The solvent used in the reaction is selected from one or more of 2-methyltetrahydrofuran, acetonitrile, dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, methyl tert-butyl ether, ethyl ether, acetone, benzene, deuterated benzene, toluene, deuterated toluene, p-xylene, o-xylene, m-xylene, ethylbenzene, tetrahydrofuran and 1,4-dioxane.

7. The preparation method according to claim 1 or 2, characterized in that: The compound represented by formula (2) is selected from vinyl bromide.

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