A method for synthesizing 2-arylpropionic acid compounds

Abstract

The invention provides a method for synthesizing 2-aryl propionic acid compounds, and relates to the field of biomedical technology. In the present invention, under the condition of visible light of 400-480nm, compound a and compound b are used as raw materials, and a ligand c, a copper catalyst and a base are reacted in a solvent to obtain compound d, which is a 2-aryl propionic acid ester compound. The present application has the advantages of cheap and easy to obtain raw materials, convenient generation, mild conditions, environmental safety, good compatibility of functional groups, and recyclable copper catalysts, which greatly reduces production costs.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedicine, and specifically relates to a method for synthesizing 2-arylpropionic acid compounds. Background Art

[0002] Nonsteroidal anti-inflammatory drugs are a class of anti-inflammatory drugs that do not contain steroidal structures. They are named to distinguish them from glucocorticoids (steroidal anti-inflammatory drugs). Arylpropionic acids are a very important class of nonsteroidal anti-inflammatory drugs. Common arylpropionic acid nonsteroidal anti-inflammatory drugs include:

[0003]

[0004] Aryl propionic acid non-steroidal anti-inflammatory drugs have anti-inflammatory, anti-rheumatic, analgesic, antipyretic and anticoagulant effects. They are widely used in the clinic to relieve osteoarthritis, rheumatoid arthritis, various fevers and various pain symptoms. Their anti-inflammatory mechanism is different from that of glucocorticoid steroidal anti-inflammatory drugs. They mainly inhibit the cyclooxygenase-mediated conversion of arachidonic acid to thromboxane and various prostaglandins (PGs) to achieve anti-inflammatory, analgesic and antipyretic effects. At present, there are many methods for obtaining aryl propionic acid non-steroidal anti-inflammatory drugs, mainly including epoxycarboxylate method, daptomycin condensation method and α-halopropionylnaphthalene rearrangement method. However, these synthesis methods all have certain disadvantages, which in turn limits their industrial application. For example, the epoxy carboxylate method requires Friedel-Crafts reaction, Darzens condensation, hydrolysis, neutralization, and decarboxylation to obtain isobutylphenylpropionaldehyde, which is then oxidized or first generated by oxime and then eliminated and hydrolyzed to obtain ibuprofen. This synthesis method has too many steps, is too cumbersome, and has high production costs. The Darzens condensation method and the α-halopropionyl naphthalene rearrangement method are currently the commonly used methods for producing naproxen in China. Although they can meet the requirements of low cost and high yield, they have the disadvantages of difficult control of side reactions and high toxicity of reaction solvents. In recent decades, the invention and application of the Suzuki coupling reaction have provided new ideas and methods for the synthesis of 2-arylpropionic acid compounds.

[0005] At present, similar compounds to the target product of the present invention have been reported, such as:

[0006] Route 1:

[0007]

[0008] This route uses isobutylbenzene as a raw material, reacts in the presence of HF and (CH3CO)2O to obtain p-isobutylacetophenone, which is then reduced by hydrogenation to generate 1-(4-isobutylphenyl)ethanol, and finally undergoes carbonylation to synthesize ibuprofen. This synthesis method has too many steps and the reaction process is slightly complicated.

[0009] Route 2:

[0010]

[0011] The synthetic route is to use isobutylbenzene as a raw material, react with acetaldehyde, hydrochloric acid, and zinc chloride to generate 1-p-isobutylphenyl-1-chloroethane, and then react with carbon monoxide under alkaline conditions (or acidic conditions) to undergo a halogenated hydrocarbon carbonylation reaction, and finally generate the ibuprofen product. The carbonylation reaction conversion rate of this method is relatively high; however, generally, ibuprofen salt is obtained under alkaline conditions, and further acidification is required to obtain ibuprofen, and the steps are relatively cumbersome. In addition, a large number of by-products will be generated during the carbonylation process.

[0012] Route 3:

[0013]

[0014] This method uses aromatic substituted olefins, CO, H2O and alcohol as raw materials, and reacts under palladium catalysis and acidic conditions to obtain ibuprofen. This reaction requires the use of precious metal palladium as a catalyst, which seriously limits its large-scale use in industry and the pharmaceutical industry. In addition, the isomer 3-(4-isobutylphenyl) propionic acid is generated during the reaction.

[0015] Therefore, developing a universal, simple, green and environmentally friendly new method to synthesize 2-arylpropionic acid compounds to replace the above and existing synthesis processes is of great significance for the industrial production of 2-arylpropionic acid compounds and their derivatives. Summary of the invention

[0016] In order to solve the above technical problems, the present invention provides a method for synthesizing 2-arylpropionic acid compounds. The method uses a cheap and readily available metal copper catalyst instead of a noble metal catalyst, and has the advantages of cheap and readily available raw materials, simple operation, and suitability for industrial production.

[0017] A method for synthesizing 2-aryl propionic acid compounds, using compound a and compound b as raw materials, reacting in a solvent in the presence of ligand c, a copper catalyst and a base under visible light conditions of 400-480 nm to obtain compound d, which is a 2-aryl propionic acid ester compound: the general reaction formula is as follows:

[0018]

[0019] In the above reaction formula, Ln is a ligand, Cu-catalyst is a copper catalyst, Base is a base, and Slovent is a solvent;

[0020] The base is one or more of a carbonate inorganic base and a tertiary amine organic base;

[0021] R1 is one of phenyl, monosubstituted phenyl, polysubstituted phenyl, naphthyl, substituted naphthyl, pyridyl, indolyl and furanyl;

[0022] R2 is an alkyl group having only 1 to 10 carbon atoms or an alkyl group having 1 to 10 carbon atoms and containing an ether bond;

[0023] R3 is a benzyl group or a benzyl group having a substituent or an alkyl group having only 1 to 10 carbon atoms.

[0024] Preferably, the substituents in the monosubstituted phenyl group and the polysubstituted phenyl group are selected from branched and / or straight-chain alkyl groups having 1 to 10 carbon atoms, N,N-dimethylamino groups, alkoxy groups having 1 to 10 carbon atoms, trifluoromethoxy groups, halogen groups, trifluoromethyl groups, formyl groups, acetyl groups, ester groups, cyano groups, ethynyl groups, carboxyl groups, phenyl groups, and benzoyl groups.

[0025] Preferably, the substituent in the substituted naphthyl group is an alkoxy group having 1 to 10 carbon atoms.

[0026] Preferably, the copper catalyst is cuprous iodide, cuprous bromide, cuprous chloride, cupric chloride, cupric oxide, cupric bromide, cupric fluoride, cupric iodide, copper levulinate, zinc copper reagent, copper trifluoromethanesulfonate, copper fluoroborate, tetraethylcyanocopper hexafluorophosphate, cupric acetate, activated copper, or cuprous sulfide.

[0027] Preferably, the ligand c is one or more of 3,3'-biisoquinoline, 2,2':6',2"-tripyridine, 4,7-diphenyl-1,10-phenanthroline, 4,4'-di-tert-butyl-2,2'-bipyridine, 2,2'-bipyrimidine, 4-4'-dimethyl-2,2'-bipyridine, 5-5'-dimethyl-2,2'-bipyridine, 6-6'-dimethyl-2,2'-bipyridine, 1,10-phenanthroline-5,6-dione, and 4-bromo-5'-phenyl-1,1':3',1"-terphenyl;

[0028] Preferably, the base is one or more of cesium carbonate, lithium carbonate, sodium carbonate, potassium carbonate, sodium hydroxide, sodium acetate, N,N-diisopropylmethylamine, N,N-diisopropylethylamine, potassium tert-butoxide, lithium tert-butoxide, sodium tert-butoxide, potassium hydroxide, K3PO4, K2HPO4, KH2PO4, and KF.

[0029] Preferably, the compound a is 4-acetylphenylboronic acid, 4-methylphenylboronic acid, 3-methylphenylboronic acid, 4-tert-butylphenylboronic acid, 4-cyanophenylboronic acid, 4-ethynylphenylboronic acid, 4-(dimethylamino)phenylboronic acid, 4-formylphenylboronic acid, 4-methoxycarbonylphenylboronic acid, 4-ethoxyphenylboronic acid, 6-methoxy-2-naphthaleneboronic acid, 4-iodophenylboronic acid, 4-chlorophenylboronic acid, 4-bromophenylboronic acid, 4-fluorophenylboronic acid, 1-naphthalenephenylboronic acid, pyridine-4-boric acid, pyridine-3-boric acid, 3-thiopheneboric acid, 3-furanboric acid, pyridine-2-boric acid , 2-cyanophenylboric acid, 2-formylphenylboric acid, 3-formylphenylboric acid, 3-acetylphenylboric acid, 4-ethoxycarbonylphenylboric acid, 3-ethoxycarbonylphenylboric acid, 3-formyl-4-methoxyphenylboric acid, 3-methoxy-4-methoxycarbonylphenylboric acid, 3-fluoro-4-methoxycarbonylphenylboric acid, 4-benzoylphenylboric acid, 4-(N-methylformamide)phenylboric acid, 4-trifluoromethoxyphenylboric acid, 3-carboxylphenylboric acid, 4-carboxylphenylboric acid, 4-carbamoylphenylboric acid, 4-trifluoromethylphenylboric acid, phenylboric acid and 4-biphenylboric acid;

[0030] Preferably, the compound b is one of methyl 2-bromopropionate, methyl 2-bromo-3-methoxypropionate, tert-butyl 2-bromopropionate, methyl 2,3-dibromopropionate, methyl 2-bromohexanoate, methyl 2-bromobutyrate, ethyl 2,3-dibromopropionate, methyl 2-bromoisobutyrate, methyl 2,4-dibromobutyrate, ethyl 2-bromobutyrate, ethyl 2,3-dibromobutyrate, tert-butyl 2-bromoisobutyrate, methyl 2-bromooctanoate, ethyl 2-bromoisovalerate and ethyl 2-bromoisobutyrate.

[0031] Preferably, the solvent is any one or more of dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, 1,4-dioxane, tetrahydrofuran, dichloromethane, acetonitrile, triethylamine, ethyl acetate, methanol, xylene, n-hexane, pyridine and isopropanol.

[0032] Preferably, the molar ratio of compound a, compound b, copper catalyst, ligand c and base is 1:(1-3):(0.1-0.15):(0.11-0.165):(1-3).

[0033] Preferably, the molar ratio of compound a, compound b, copper catalyst, ligand c and base is 1:2:0.1:0.11:2.

[0034] Preferably, the visible light is blue light with a wavelength of 400 nm.

[0035] Preferably, the reaction temperature is 20-30°C.

[0036] Preferably, the reaction is carried out in an inert gas or nitrogen atmosphere.

[0037] Compared with the prior art, the present invention has the following beneficial effects:

[0038] The reaction principle in the present application is: the ligand in the present application is complexed with the copper catalyst to generate a monovalent copper catalyst intermediate A, and then, the aryl boronic acid compound a undergoes a transmetallation reaction with the monovalent copper catalyst intermediate A under the action of a base to obtain a complex B, and the complex B is irradiated with 400-480nm blue light to obtain an excited state complex B'; and the complex B' and the compound b undergo a redox reaction to generate alkyl radicals b', Br - and a divalent copper catalyst intermediate C, in the step of reacting the complex B' with the compound b, the complex B' acts as both a raw material and a photocatalyst, and then the divalent copper catalyst intermediate C captures the alkyl radical b' to generate a trivalent copper complex D, and then the trivalent copper complex D itself is reduced and eliminated to obtain the target product d and a monovalent copper catalyst intermediate A. From the reaction principle, the method claimed in the present application has the advantage that the monovalent copper catalyst intermediate A can be reused.

[0039] In addition, the preparation method of the present invention also has the advantages of cheap and easy raw materials, convenient generation, mild conditions, environmental safety, good functional group compatibility and recyclable copper catalyst, which greatly reduces the production cost; moreover, the experimental operation in the present application is simple, less waste is generated, and the environmental protection is good. During the reaction process, all raw materials and catalysts can be dissolved in the solvent, and the reaction is a homogeneous reaction, which is more suitable for industrial production; in addition, the present application also screens and optimizes the synthesis conditions such as the reaction solvent, the base used, the catalyst, and the reaction temperature and time, which further improves the reaction yield. Among them, the yield of 2-aryl propionate compounds can reach up to 85.6%. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] Figure 1 The reaction principle diagram of this application;

[0041] Figure 2 This is the hydrogen spectrum of the target product in Example 1;

[0042] Figure 3 This is the carbon spectrum of the target product in Example 1;

[0043] Figure 4 This is the hydrogen spectrum of the target product of Example 2;

[0044] Figure 5 This is the carbon spectrum of the target product of Example 2;

[0045] Figure 6 This is the hydrogen spectrum of the target product of Example 3;

[0046] Figure 7This is the carbon spectrum of the target product of Example 3;

[0047] Figure 8 This is the hydrogen spectrum of the target product of Example 4;

[0048] Fig. 9 This is the carbon spectrum of the target product of Example 4. DETAILED DESCRIPTION

[0049] The following examples set forth preferred embodiments of the present invention, however, it should be understood that these examples are provided for illustration purposes only and are not intended to limit the overall scope of the invention.

[0050] In the embodiment, the nuclear magnetic resonance spectroscopy 1 H-NMR and 13 C-NMR was measured using a 600 MHz nuclear magnetic resonance spectrometer from Bruker.

[0051] The raw materials used in the following examples were purchased from the market.

[0052] Example 1

[0053] Target compound structure:

[0054]

[0055] In a nitrogen atmosphere, 4-acetylphenylboronic acid (32.8 mg, 0.2 mmol) and methyl 2-bromopropionate (45.4 ul, 0.4 mmol) were added to a Shrek reaction tube with a magnet, and then CuI catalyst (4 mg, 0.02 mmol, 11%), ligand 4,7-diphenyl-1,10-phenanthroline (7.3 mg, 0.022 mmol, 11%), and Cs2CO3 (130 mg, 0.4 mmol) were added in sequence. Finally, 2 ml of CH3CN and 0.1 ml of H2O were added to the reaction tube. After the reaction tube was sealed with a rubber stopper, it was placed on a stirrer irradiated with blue light of a wavelength of 400 nm and reacted at room temperature of 25 degrees for 24 hours. After the reaction, petroleum ether: ethyl acetate in a volume ratio of 5:1 was used as the developing solvent, and the reaction product was determined by thin layer chromatography. Then, a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 30:1, 20:1, and 10:1 was used as the eluent to separate by gradient silica gel column, and the target product (85.6% yield) was obtained. The hydrogen spectrum and carbon spectrum of the target product are Figure 2 and Figure 3 , the NMR spectrum data are: 1H NMR (600MHz, CDCl3) δ: 7.85 (d, J = 8.9 Hz, 2H), 6.82 (d, J = 8.9 Hz, 2H), 4.78 (q, J = 6.8 Hz, 1H), 3.69 (s, 3H), 2.47 (s, 3H), 1.58 (d, J = 6.8 Hz, 3H). 13 C NMR (151MHz, CDCl3) δ: 195.7, 171.0, 160.3, 130.0, 129.6, 113.5, 71.4, 51.5, 17.4.

[0056] Example 2

[0057] Target compound structure:

[0058]

[0059] In a nitrogen atmosphere, 4-cyanophenylboronic acid (29.4 mg, 0.2 mmol) and methyl 2-bromopropionate (45.4 ul, 0.4 mmol) were added to a Shrek reaction tube with a magnet, and then CuBr catalyst (2.9 mg, 0.02 mmol, 11%), ligand 4,7-diphenyl-1,10-phenanthroline (7.3 mg, 0.022 mmol, 11%) and Cs2CO3 (130 mg, 0.4 mmol) were added in sequence. Finally, 2 ml of CH3CN and 0.1 ml of H2O were added to the reaction tube. After the reaction tube was sealed with a rubber stopper, it was placed on a stirrer irradiated with blue light of a wavelength of 400 nm and reacted at room temperature of 25 degrees for 24 hours. After the reaction, petroleum ether: ethyl acetate in a volume ratio of 5:1 was used as the developing solvent, and the reaction product was determined by thin layer chromatography. Then, a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 30:1, 20:1, and 10:1 was used as the eluent to separate by gradient silica gel column, and the target product (83.4% yield) was obtained. The hydrogen spectrum and carbon spectrum of the target product are Figure 4 and Figure 5 , the NMR spectrum data are: 1 H NMR (600MHz, CDCl3) δ: 7.51 (d, J = 8.9 Hz, 2H), 6.84 (d, J = 8.9 Hz, 2H), 4.75 (q, J = 6.8 Hz, 1H), 3.70 (s, 3H), 1.59 (d, J = 6.8 Hz, 3H). 13 C NMR (151MHz, CDCl3) δ: 170.6, 159.7, 133.1, 117.9, 114.6, 103.9, 51.6, 17.4.

[0060] Example 3

[0061] Target compound structure:

[0062]

[0063] In a nitrogen atmosphere, 4-formylphenylboronic acid (30 mg, 0.2 mmol) and methyl 2-bromopropionate (45.4 ul, 0.4 mmol) were added to a Shrek reaction tube with a magnet, and then CuCl catalyst (2 mg, 0.02 mmol, 11%), ligand 4,7-diphenyl-1,10-phenanthroline (7.3 mg, 0.022 mmol, 11%) and Cs2CO3 (130 mg, 0.4 mmol) were added in sequence. Finally, 2 ml of CH3CN and 0.1 ml of H2O were added to the reaction tube. After the reaction tube was sealed with a rubber stopper, it was placed on a stirrer irradiated with blue light of a wavelength of 400 nm and reacted at room temperature of 25 degrees for 24 hours. After the reaction, petroleum ether: ethyl acetate in a volume ratio of 5:1 was used as the developing solvent, and the reaction product was determined by thin layer chromatography. Then, a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 30:1, 20:1, and 10:1 was used as the eluent to separate by gradient silica gel column, and the target product (yield of 72.8%) was obtained. The hydrogen spectrum and carbon spectrum of the target product are Figure 6 and Figure 7 , the NMR spectrum data are: 1 H NMR (600MHz, CDCl3) δ: 9.81 (s, 1H), 7.76 (d, J = 8.8Hz, 2H), 6.89 (d, J = 8.7Hz, 2H), 4.80 (q, J = 6.8Hz, 1H), 3.70 (s, 3H), 1.59 (d, J = 6.8Hz, 3H). 13 C NMR (151MHz, CDCl3) δ: 189.7, 170.8, 161.4, 131.0, 129.6, 114.1, 71.5, 51.5, 17.4.

[0064] Example 4

[0065] Target compound structure:

[0066]

[0067] In a nitrogen atmosphere, 4-methoxycarbonylphenylboronic acid (36 mg, 0.2 mmol) and methyl 2-bromopropionate (45.4 ul, 0.4 mmol) were added to a Shrek reaction tube with a magnet, and then CuI catalyst (4 mg, 0.02 mmol, 11%), ligand 5-5' dimethyl-2, 2'-bipyridine (2.1 mg, 0.022 mmol, 11%) and Cs2CO3 (130 mg, 0.4 mmol) were added in sequence. Finally, 2 ml CH3CN and 0.1 ml H2O were added to the reaction tube. After the reaction tube was sealed with a rubber stopper, it was placed on a stirrer irradiated with blue light of a wavelength of 400 nm and reacted at room temperature of 25 degrees for 24 hours. After the reaction, petroleum ether: ethyl acetate in a volume ratio of 5:1 was used as the developing solvent, and the reaction product was determined by thin layer chromatography. Then, petroleum ether and ethyl acetate mixed solvents in a volume ratio of 30:1, 20:1, and 10:1 were used as the eluents to perform gradient separation on a silica gel column to obtain the target product (80.5% yield). The hydrogen spectrum and carbon spectrum of the target product are Figure 8 and Fig. 9 , the NMR spectrum data are: 1 H NMR (600MHz, CDCl3) δ: 7.98 (d, J = 9.0Hz, 2H), 6.88 (d, J = 8.9Hz, 2H), 4.84 (q, J = 6.8Hz, 1H), 3.88 (s, 3H), 3.76 (s, 3H), 1.65 (d, J = 6.8Hz, 3H). 13 C NMR (151MHz, CDCl3) δ: 169.7, 164.3, 158.8, 129.3, 121.1, 112.1, 50.1, 49.6, 16.1.

[0068] Example 5

[0069] Target compound structure:

[0070]

[0071] In a nitrogen atmosphere, 4-ethoxycarbonylphenylboronic acid (38.8 mg, 0.2 mmol) and methyl 2-bromopropionate (45.4 ul, 0.4 mmol) were added to a Shrek reaction tube with a magnet, and then CuI catalyst (4 mg, 0.02 mmol, 11%), ligand 4,7-diphenyl-1,10-phenanthroline (7.3 mg, 0.022 mmol, 11%) and K2CO3 (55.2 mg, 0.4 mmol) were added in sequence. Finally, 2 ml of CH3CN and 0.1 ml of H2O were added to the reaction tube. After the reaction tube was sealed with a rubber stopper, it was placed on a stirrer irradiated with blue light of a wavelength of 400 nm and reacted at room temperature of 25 degrees for 24 hours. After the reaction, petroleum ether: ethyl acetate in a volume ratio of 5:1 was used as the developing solvent, and the reaction product was determined by thin layer chromatography. Then, petroleum ether and ethyl acetate mixed solvents in a volume ratio of 30:1, 20:1, and 10:1 were used as eluents to perform gradient separation on a silica gel column to obtain the target product (63.6% yield). After testing, the nuclear magnetic resonance spectrum data of the target product were: 1 H NMR (600MHz, CDCl3) δ: 7.91 (d, J=8.8Hz, 2H), 6.80 (d, J=8.8Hz, 2H), 4.76 (q, J=6.8Hz, 1H), 4.26 (q, J = 7.1Hz, 2H), 3.68 (s, 3H), 1.57 (d, J = 6.8Hz, 3H), 1.29 (t, J = 7.2Hz, 3H). 13 C NMR (151MHz, CDCl3) δ: 172.1, 166.2, 161.1, 131.6, 123.8, 114.4, 72.4, 60.7, 52.5, 18.5, 14.4.

[0072] Example 6

[0073] Target compound structure:

[0074]

[0075] In a nitrogen atmosphere, 4-benzoylphenylboronic acid (45.2 mg, 0.2 mmol) and methyl 2-bromopropionate (45.4 ul, 0.4 mmol) were added to a Shrek reaction tube with a magnet, and then CuI catalyst (4 mg, 0.02 mmol, 11%), ligand 4,7-diphenyl-1,10-phenanthroline (7.3 mg, 0.022 mmol, 11%) and Na2CO3 (42.4 mg, 0.4 mmol) were added in sequence. Finally, 2 ml of CH3CN and 0.1 ml of H2O were added to the reaction tube. After the reaction tube was sealed with a rubber stopper, it was placed on a stirrer irradiated with blue light of a wavelength of 400 nm and reacted at room temperature of 25 degrees for 24 hours. After the reaction, petroleum ether: ethyl acetate in a volume ratio of 5:1 was used as the developing solvent, and the reaction product was determined by thin layer chromatography. Then, petroleum ether and ethyl acetate mixed solvents in a volume ratio of 30:1, 20:1, and 10:1 were used as the eluents to perform gradient separation on a silica gel column to obtain the target product (56.0% yield). After testing, the nuclear magnetic resonance spectrum data of the target product were: 1 H NMR(600MHz, CDCl3)δ:7.73(d,J=8.9Hz,2H),7.67(d,J=8.3Hz,2H),7.48(t,J=7.4Hz,1H),7.39( t,J=7.7Hz,2H),6.85(d,J=8.9Hz,2H),4.79(q,J=6.8Hz,1H),3.70(s,3H),1.59(d,J=6.8Hz,3H). 13 C NMR (151MHz, CDCl3) δ: 195.5, 172.1, 161.1, 138.1, 132.6, 132.0, 130.9, 129.8, 128.2, 114.4, 72.5, 52.5, 18.5.

[0076] In addition, the present application also implemented Examples 7 to 39 respectively according to the method of Example 1. In Examples 7 to 39, only the reaction raw materials (i.e., compound a and compound b) are different from Example 1, and other raw materials, conditions and operations remain unchanged. The target compounds, yields of the target compounds, and the statistics of the R1, R2, and R3 groups in Compound a and Compound b shown in Examples 7 to 39 are shown in Table 1;

[0077] Table 1

[0078]

[0079]

[0080]

[0081]

[0082]

[0083]

[0084] Combining the yield data shown in Table 1 and Examples 1-6, it can be seen that in this application, whether it is Examples 7-39 or Examples 1-6 that use the method described in Example 1 to synthesize a series of 2-aryl propionate compounds, the yield can reach above medium, which shows that the reaction raw materials and functional groups of the method described in this application are widely applicable. Moreover, from Examples 1-39, the yield of preparing 2-aryl propionate compounds using the method described in this application can reach up to 85.6%. The yield is good; and the reaction time of this application is short, so it also has the advantages of efficient and fast reaction.

Claims

1. A method for synthesizing 2-arylpropionic acid compounds, characterized in that: Under the condition of 400nm blue light, compound a and compound b are used as raw materials, and react in a solvent in the presence of ligand c, copper catalyst and base to obtain compound d, which is a 2-aryl propionate compound. The general reaction formula is as follows: The copper catalyst is cuprous iodide, cuprous bromide or cuprous chloride; The ligand c is 4,7-diphenyl-1,10-phenanthroline or 5-5'-dimethyl-2,2'-bipyridine; The base is one or more of cesium carbonate, lithium carbonate, sodium carbonate, potassium carbonate, sodium hydroxide, sodium acetate, N,N-diisopropylmethylamine, N,N-diisopropylethylamine, potassium tert-butoxide, lithium tert-butoxide, sodium tert-butoxide, potassium hydroxide, K3PO4, K2HPO4, KH2PO4, and KF; The compound a is 4-acetylphenylboronic acid, 4-methylphenylboronic acid, 3-methylphenylboronic acid, 4-tert-butylphenylboronic acid, 4-cyanophenylboronic acid, 4-ethynylphenylboronic acid, 4-(dimethylamino)phenylboronic acid, 4-formylphenylboronic acid, 4-methoxycarbonylphenylboronic acid, 4-ethoxyphenylboronic acid, 4-iodophenylboronic acid, 4-chlorophenylboronic acid, 4-bromophenylboronic acid, 4-fluorophenylboronic acid, 2-cyanophenylboronic acid, 2-formylphenylboronic acid, 3-formylphenylboronic acid, 3-acetylphenylboronic acid, 4-ethoxycarbonylphenylboronic acid, 3-ethoxycarbonylphenylboronic acid, one of 3-(4-(N-methylformamide)phenylboronic acid, 4-(trifluoromethoxy)phenylboronic acid, 3-(4-(4-(N-methylformamide)phenylboronic acid, 4-(trifluoromethoxy)phenylboronic acid, 3-(4-(N-methylformamide)phenylboronic acid, 4-(trifluoromethoxy)phenylboronic acid, 3-(4-(N-methylformamide)phenylboronic acid, 4-(trifluoromethoxy)phenylboronic acid, 3-(4-(N-methylformamide)phenylboronic acid, 4-(trifluoromethoxy)phenylboronic acid, 3-(4-(N-methylformamide)phenylboronic acid, 4-(trifluoromethyl ... The compound b is one of methyl 2-bromopropionate, methyl 2-bromo-3-methoxypropionate, tert-butyl 2-bromopropionate, methyl 2,3-dibromopropionate, methyl 2-bromohexanoate, methyl 2-bromobutyrate, ethyl 2,3-dibromopropionate, methyl 2-bromoisobutyrate, methyl 2,4-dibromobutyrate, ethyl 2-bromobutyrate, ethyl 2,3-dibromobutyrate, tert-butyl 2-bromoisobutyrate, methyl 2-bromooctanoate, ethyl 2-bromoisovalerate and ethyl 2-bromoisobutyrate; The reaction is carried out in an inert gas atmosphere.

2. The method for synthesizing 2-arylpropionic acid compounds according to claim 1, characterized in that: The molar ratio of compound a, compound b, copper catalyst, ligand c and base is 1:(1-3):(0.1-0.15):(0.11-0.165):(1-3).

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