Synthetic method of indene acetate compound

Abstract

The invention discloses a synthetic method of an indene acetate compound, and the reaction formula of the synthetic method is as follows: in the # imgabs0 # formula, R1 is selected from alkyl, alkoxy, trifluoromethyl, cyano, acetyl or halogen; r2 and R3 are selected from aryl or alkyl; ar is an aryl group; the synthesis method comprises the following synthesis steps: taking halogenated aryl ethylene, diaryl alkyne and formate as raw materials, reacting in an organic solvent under the combined action of a palladium catalyst, a ligand and alkali, and after the reaction is finished, performing post-treatment to obtain the indene acetate compound. Three carbon-carbon bonds and one ring are constructed through one pot, and the method has the advantages that operation is easy, raw materials are easy to obtain, substrate applicability is wide, and target products are easy to separate.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing indenyl acetate compounds. Background Art

[0002] Indene derivatives have attracted extensive attention in the fields of medicinal chemistry, organic chemistry and materials science due to their unique biological activities, chemical and physical properties. In this context, chemists have developed some effective construction methods. Typical strategies include nucleophilic attack-induced cyclization, intramolecular electrophilic substitution reactions, ring expansion and contraction, and transition metal-catalyzed cyclization. Among them, palladium-catalyzed cross-coupling cyclization has become a powerful tool for obtaining indene derivatives. For example, Feng Xiaoming's research group developed a practical synthetic route to construct highly functionalized 1-trifluoromethyl-1H-indene through a fluorine nucleophilic addition-induced [3+2] cyclization strategy. However, the existing methods still have the problems of limited substrate range and poor product diversity. In addition, the current reactions have a large waste of substrates and a large variety of by-products output by the reaction. In particular, when introducing different types of functional groups into the indene skeleton, there are great difficulties and substrate limitations. Therefore, it is of great significance to develop efficient new methods with a wide substrate range to assemble functionalized indene derivatives.

[0003] In summary, in view of the various shortcomings of the existing preparation methods, developing an effective method for preparing indenyl acetate with safe and readily available raw materials and strong substrate universality has important research significance and practical application value. Summary of the invention

[0004] The invention aims to provide a method for synthesizing indenyl acetate compounds to solve the problems of limited substrate range and poor product diversity.

[0005] To achieve the above object, the present invention adopts the following technical solution:

[0006] A method for synthesizing an indenyl acetate compound, wherein the reaction formula of the synthetic method is as follows:

[0007]

[0008] In the formula, R 1 is selected from alkyl, alkoxy, trifluoromethyl, cyano, acetyl or halogen; R 2 and R 3 is selected from aryl or alkyl; Ar is aryl;

[0009] The synthesis steps are: using halogenated arylethylene, diaryl alkyne and formate as raw materials, reacting in an organic solvent under the joint action of a palladium catalyst, a ligand and a base, and obtaining an indenyl acetate compound through post-treatment after the reaction is completed.

[0010] The specific steps of the synthesis method are:

[0011] The first step: adding halogenated arylethylene, diaryl alkyne and formate into a reaction vessel, adding palladium catalyst, ligand, base and organic solvent in sequence, heating to 60-90°C for reaction under stirring conditions, and the reaction time is 8-16 hours; preferably, the reaction temperature is 70°C and the reaction time is 12 hours;

[0012] Step 2: Detect the progress of the reaction by thin layer chromatography, and terminate the reaction when there is no raw material in the reaction system; obtain indenyl acetate compounds through post-treatment.

[0013] Preferably, the palladium catalyst is one of palladium acetate, palladium chloride, palladium trifluoroacetate, bis(triphenylphosphine)palladium dichloride, allylpalladium chloride or bis(acetonitrile)palladium dichloride. More preferably, the palladium catalyst is bis(acetonitrile)palladium dichloride.

[0014] Preferably, the ligand is one of a bidentate phosphine ligand, a trialkylphosphine ligand or a triarylphosphine ligand derivative. More preferably, the ligand is 2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl.

[0015] Preferably, the base is one of potassium acetate, cesium acetate, potassium carbonate, sodium acetate, cesium carbonate and potassium phosphate. More preferably, the base is potassium carbonate.

[0016] Preferably, the organic solvent is one of ethylene glycol dimethyl ether, toluene, dioxane, tetrahydrofuran or 1,2-dichloroethane. More preferably, the organic solvent is ethylene glycol dimethyl ether.

[0017] Preferably, the halogenated aromatic vinyl is 1-iodine-2-(prop-1-en-2-yl)benzene, 1-iodine-4-methyl-2-(prop-1-en-2-yl)benzene, 4-fluoro-1-iodine-2-(prop-1-en-2-yl)benzene, 4-chloro-1-iodine-2-(prop-1-en-2-yl)benzene, 1-iodine-2-(prop-1-en-2-yl)-4-(trifluoromethyl)benzene, 2-iodine-4-methoxy-1-(prop-1-en-2-yl)benzene, 4-chloro-2-iodine-1-(prop-1-en-2-yl)benzene, 4-fluoro-2-iodine-1-(prop-1-en-2-yl)benzene, 2-iodine-1-methyl-3-(prop-1-en-2-yl)benzene, 1-(but-1-en-2-yl)benzene )-2-iodobenzene, 1-(hex-1-en-2-yl)-2-iodobenzene; the diaryl alkyne is 1,2-diphenylacetylene, 1,2-di-p-tolueneacetylene, 1,2-bis(4-(tert-butyl)phenyl)acetylene, 1,2-bis(4-methoxyphenyl)acetylene, 1,2-bis(3-fluorophenyl)acetylene, 1,2-bis(3-chlorophenyl)acetylene, 1,2-bis(3-methoxyphenyl)acetylene, etc.; the formic acid ester is one of phenyl formate, p-tolyl formate, p-methoxyphenyl formate, 4-fluorophenyl formate, 4-chlorophenyl formate, 3-fluorophenyl formate, 3-chlorophenyl formate, 3-methoxyphenyl formate, 3-methylphenyl formate, 2-methylphenyl formate, and 2-methoxyphenyl formate.

[0018] Preferably, the molar ratio of the halogenated arylethylene, diaryl alkyne, formate, palladium catalyst, ligand, and base is 0.1:0.2:0.3:0.01:0.02:0.3; and the concentration of the halogenated arylethylene in the reaction solution is 0.2 mol / L.

[0019] Preferably, the post-treatment step is: after the reaction is completed, the reaction system is cooled, the organic solvent is removed by rotary evaporation under reduced pressure, and the residue is mixed with silica gel and separated by column chromatography to obtain indenyl acetate compounds.

[0020] Preferably, the eluent for the column chromatography is a mixture of petroleum ether and ethyl acetate in a volume ratio of 20:1 to 5:1.

[0021] Beneficial effects: Compared with the prior art, the present invention has the following advantages:

[0022] 1. The present invention has the advantages of low reaction cost, safe and readily available raw materials, good functional group tolerance, and wide substrate universality;

[0023] 2. The three reaction substrates are assembled into the target molecule, with only one iodine atom falling off, resulting in high atomic utilization;

[0024] 4. Compared with the prior art, the present invention can combine indene with biologically active molecules to achieve the synthesis of active molecules with similar structures, such as carvacrol, flavonoids, raspberry ketone, tocopherol, pterostilbene and estrone. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 The product compound 4a of Example 1 1 H NMR spectrum;

[0026] Figure 2 The product compound 4a of Example 1 13 C NMR spectrum;

[0027] Figure 3 The product compound 4b of Example 2 1 H NMR spectrum;

[0028] Figure 4 The product compound 4b of Example 2 13 C NMR spectrum;

[0029] Figure 5 The product compound 4c of Example 3 1 H NMR spectrum;

[0030] Figure 6 The product compound 4c of Example 3 13 C NMR spectrum;

[0031] Figure 7 The product compound 4d of Example 4 1 H NMR spectrum;

[0032] Figure 8 The product compound 4d of Example 4 13 C NMR spectrum;

[0033] Fig. 9 The product compound 4e of Example 5 1 H NMR spectrum;

[0034] Fig.10 The product compound 4e of Example 5 13 C NMR spectrum;

[0035] Fig.11 The product compound 4f of Example 6 1 H NMR spectrum;

[0036] Fig.12 The product compound 4f of Example 6 13 C NMR spectrum;

[0037] Fig.13 The product compound 4g of Example 7 1 H NMR spectrum;

[0038] Fig.14 The product compound 4g of Example 7 13 C NMR spectrum;

[0039] Fig.15 The product compound 4h of Example 8 1 H NMR spectrum;

[0040] Fig.16 The product compound 4h of Example 8 13 C NMR spectrum;

[0041] Fig.17 The product compound 4i of Example 91 1 H NMR spectrum;

[0042] Fig.18 The product compound 4i of Example 9 13 C NMR spectrum;

[0043] Fig.19 The product compound 4j of Example 10 1 H NMR spectrum;

[0044] Fig. 20 The product compound 4j of Example 10 13 C NMR spectrum;

[0045] Fig.21 The product compound 4k of Example 11 1 H NMR spectrum;

[0046] Fig. 22 The product compound 4k of Example 11 13 CNMR spectrum. DETAILED DESCRIPTION

[0047] The present invention will be further explained below in conjunction with the embodiments.

[0048] The present invention can be better understood according to the following examples. However, it is easy for those skilled in the art to understand that the specific material ratios, process conditions and results described in the examples are only used to illustrate the present invention.

[0049] Example 1: Preparation of Compound 4a

[0050]

[0051] 1-iodo-2-(prop-1-en-2-yl)benzene (48.6 mg, 0.2 mmol), 1,2-diphenylacetylene (71.2 mg, 0.4 mmol), phenyl formate (73.2 mg, 0.6 mmol), bis(acetonitrile)palladium dichloride (5.2 mg, 0.02 mmol), 2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl (19.08 mg, 0.04 mmol) and potassium carbonate (82.4 mg, 0.6 mmol) were added to a 25 mL reaction bottle. Then 1.0 ml of ethylene glycol dimethyl ether was added, sealed, and stirred in an oil bath at 70°C for 12 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and then separated by column chromatography (petroleum ether / ethyl acetate = 20:1-10:1, v / v) to obtain a colorless liquid (51 mg, yield 61%).

[0052] 1 HNMR(400MHz, CDCl3)δ7.52-7.48(m,1H),7.30(dd,J=6.3,2.6Hz,1H),7.27-7.12(m, 14H),7.03(t,J=7.5Hz,1H),6.52-6.40(m,2H),2.98(q,J=13.8Hz,2H),1.50(s,3H). 13 C{ 1 H}NMR(101MHz, CDCl3)δ169.1,150.5,150.1,149.4,143.7,140.2,136.1,134.8,130.4,129.6,129.4,128.3, 128.2,127.4,127.3,127.2,125.80,125.77,122.7,121.5,121.0,53.5,41.7,24.4.HRMS(ESI-TOF)calcdforC 30 H 25 O2[M+H] + :417.1849,found:417.1854.

[0053] Example 2: Preparation of Compound 4b

[0054]

[0055] 1-iodo-4-methyl-2-(prop-1-en-2-yl)benzene (51.4 mg, 0.2 mmol), 1,2-diphenylacetylene (71.2 mg, 0.4 mmol), phenyl formate (73.2 mg, 0.6 mmol), bis(acetonitrile)palladium dichloride (5.2 mg, 0.02 mmol), 2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl (19.08 mg, 0.04 mmol) and potassium carbonate (82.4 mg, 0.6 mmol) were added to a 25 mL reaction bottle. Then 1.0 ml of ethylene glycol dimethyl ether was added, sealed, and stirred in an oil bath at 70°C for 12 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and then separated by column chromatography (petroleum ether / ethyl acetate = 20:1-10:1, v / v) to obtain a colorless liquid (46 mg, yield 54%).

[0056] 1 HNMR (400MHz, CDCl3) δ7.38 (d, J = 1.5Hz, 1H), 7.32-7.18 (m, 13H), 7.14-7.08 (m ,2H),6.57(dd,J=8.0,1.6Hz,2H),3.08-2.97(m,2H),2.43(s,3H),1.56(s,3H). 13 C{ 1 H}NMR (101MHz, CDCl3) δ169.2,150.6,149.7,149.1,141.1,140.0,136.2,135.5,135.0,130.5,129.6,129.4,128 .2,128.12,128.05,127.2,127.1,125.7,123.6,121.5,120.7,53.3,41.8,24.5,21.8.HRMS(ESI-TOF)calcdforC 31 H 27 O2[M+H] + :431.2006,found:431.2009.

[0057] Example 3: Preparation of Compound 4c

[0058]

[0059] 2-iodo-4-methoxy-1-(prop-1-en-2-yl)benzene (54.6 mg, 0.2 mmol), 1,2-diphenylacetylene (71.2 mg, 0.4 mmol), phenyl formate (73.2 mg, 0.6 mmol), bis(acetonitrile)palladium dichloride (5.2 mg, 0.02 mmol), 2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl (19.08 mg, 0.04 mmol) and potassium carbonate (82.4 mg, 0.6 mmol) were added to a 25 mL reaction bottle. Then 1.0 ml of ethylene glycol dimethyl ether was added, sealed, and stirred in an oil bath at 70°C for 12 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and then separated by column chromatography (petroleum ether / ethyl acetate = 20:1-10:1, v / v) to obtain a colorless liquid (53 mg, yield 58%).

[0060] 1 HNMR(400MHz, CDCl3) δ7.30(d,J=8.1Hz,1H),7.23-7.11(m,12H),7.05-6.99(m,1H),6.83(d,J=2.4Hz,1H),6.77( dd,J=8.2,2.5Hz,1H),6.53-6.47(m,2H),3.71(s,3H),2.97(s,2H),1.98(q,J=7.2Hz,2H),0.58(t,J=7.2Hz,3H). 13 C{ 1 H}NMR (101MHz, CDCl3) δ169.1,159.6,150.5,148.5,146.4,139.5,136.2,130.1,129.7,129.4,128.3,12 8.2,127.3,127.2,125.7,123.1,121.5,111.2,106.8,57.4,55.6,41.7,30.3,8.2.HRMS(ESI-TOF)calcd forC 32 H 29 O3[M+H] + :461.2111,found:461.2112.

[0061] Example 4: Preparation of Compound 4d

[0062]

[0063] 2-iodo-1-methyl-3-(prop-1-en-2-yl)benzene (51.6 mg, 0.2 mmol), 1,2-diphenylacetylene (71.2 mg, 0.4 mmol), phenyl formate (73.2 mg, 0.6 mmol), bis(acetonitrile)palladium dichloride (5.2 mg, 0.02 mmol), 2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl (19.08 mg, 0.04 mmol) and potassium carbonate (82.4 mg, 0.6 mmol) were added to a 25 mL reaction bottle. Then 1.0 ml of ethylene glycol dimethyl ether was added, sealed, and stirred in an oil bath at 70°C for 12 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and then separated by column chromatography (petroleum ether / ethyl acetate = 20:1-10:1, v / v) to obtain a light yellow solid (51 mg, yield 60%).

[0064] 1 HNMR (400MHz, CDCl3) δ7.40 (d, J = 7.4Hz, 1H), 7.27-7.10 (m, 14H), 7.04 (d, J = 7. 5Hz,1H),6.59-6.52(m,2H),3.00(q,J=13.8Hz,2H),1.87(s,3H),1.54(s,3H). 13 C{ 1 H}NMR(101MHz, CDCl3)δ169.1,151.1,150.6,149.5,137.7,135.9,132.1,130.4,130.3,130.2,129.5,129.4, 127.9,127.8,127.7,127.0,126.8,125.8,125.6,121.6,120.4,52.8,41.7,24.4,20.2.HRMS(ESI-TOF)calcd forC 31 H 27 O2[M+H] + :431.2006,found:431.2006.

[0065] Example 5: Preparation of Compound 4e

[0066]

[0067] 2-iodo-1-methyl-3-(prop-1-en-2-yl)benzene (51.6 mg, 0.2 mmol), 1,2-bis(3-chlorophenyl)acetylene (98.8 mg, 0.4 mmol), phenyl formate (73.2 mg, 0.6 mmol), bis(acetonitrile)palladium dichloride (5.2 mg, 0.02 mmol), 2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl (19.08 mg, 0.04 mmol) and potassium carbonate (82.4 mg, 0.6 mmol) were added to a 25 mL reaction bottle. Then 1.0 ml of ethylene glycol dimethyl ether was added, sealed, and stirred in an oil bath at 70°C for 12 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and then separated by column chromatography (petroleum ether / ethyl acetate = 20:1-10:1, v / v) to obtain a brown liquid (45 mg, yield 47%).

[0068] 1 HNMR(400MHz, CDCl3)δ7.60-7.55(m,1H),7.39-7.32(m,4H),7.26-7.09(m,9H),7.05( m,1H),6.53-6.43(m,2H),3.11(d,J=13.8Hz,1H),3.00(d,J=13.8Hz,1H),1.55(s,3H). 13 C{ 1 H}NMR (101MHz, CDCl3) δ168.8,150.3,149.2,149.0,139.8,137.5,136.3,134.3,134.1,130.0,129.71,129.68,129.5,129 .3,128.8,127.89,127.87,127.69,127.67,126.3,125.9,122.8,121.4,121.0,53.7,41.6,24.4.HRMS(ESI-TOF)calcdforC 30 H 23 Cl2O2[M+H] + :485.1070,found:485.1071.

[0069] Example 6: Preparation of Compound 4f

[0070]

[0071] 2-iodo-1-methyl-3-(prop-1-en-2-yl)benzene (51.6 mg, 0.2 mmol), hex-3-yne (32.8 mg, 0.4 mmol), phenyl formate (73.2 mg, 0.6 mmol), bis(acetonitrile)palladium dichloride (5.2 mg, 0.02 mmol), 2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl (19.08 mg, 0.04 mmol) and potassium carbonate (82.4 mg, 0.6 mmol) were added to a 25 mL reaction bottle. Then 1.0 ml of ethylene glycol dimethyl ether was added, sealed, and stirred in an oil bath at 70°C for 12 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and then separated by column chromatography (petroleum ether / ethyl acetate = 20:1-10:1, v / v) to obtain a brown liquid (44 mg, yield 68%).

[0072] 1 HNMR (400MHz, CDCl3) δ7.35-7.31(m,1H),7.19(d,J=5.9Hz,2H),7.15-7.08(m,3H),7.03-6.98(m,1H),6.52-6.45(m,2H),2.95(d,J=13 .2Hz,1H),2.77(d,J=13.1Hz,1H),2.41(m,3H),2.28(dd,J=14.6,7.3Hz,1H),1.34(s,3H),1.11(t,J=7.7Hz,3H),1.05(t,J=7.6Hz,3H). 13 C{ 1 H}NMR (101MHz, CDCl3) δ169.1,150.5,149.5,149.1,144.3,138.7,129.2,127.1,125.6,124 .5,122.1,121.5,118.7,52.4,42.2,23.8,18.8,18.5,14.8,13.7.HRMS(ESI-TOF)calcdforC 22 H 25 O2[M+H] + :321.1849,found:321.1853.

[0073] Example 7: Preparation of Compound 4g

[0074]

[0075] 2-iodo-1-methyl-3-(prop-1-en-2-yl)benzene (51.6 mg, 0.2 mmol), 1,2-diphenylacetylene (71.2 mg, 0.4 mmol), 2,6-dimethoxybenzoate (109.2 mg, 0.6 mmol), bis(acetonitrile)palladium dichloride (5.2 mg, 0.02 mmol), 2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl (19.08 mg, 0.04 mmol) and potassium carbonate (82.4 mg, 0.6 mmol) were added to a 25 mL reaction bottle. Then 1.0 ml of ethylene glycol dimethyl ether was added, sealed, and stirred in an oil bath at 70°C for 12 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and then separated by column chromatography (petroleum ether / ethyl acetate = 20:1-10:1, v / v) to obtain a brown liquid (39 mg, yield 41%).

[0076] 1 HNMR(400MHz, CDCl3)δ7.67(dd,J=5.5,3.1Hz,1H),7.35(dd,J=5.6,3.2Hz,1H),7.30-7.18(m,12H),7.05(t,J =8.4Hz,1H),6.52(d,J=8.4Hz,2H),3.67(s,6H),3.18(d,J=15.0Hz,1H),2.91(d,J=15.0Hz,1H),1.61(s,3H). 13 C{ 1 H}NMR (101MHz, CDCl3) δ168.5,152.4,150.7,150.0,136.2,135.0,130.4,129.6,128.2,128.1,12 7.2,127.0,126.2,125.6,122.9,120.7,104.8,56.0,52.9,40.8,23.7.HRMS(ESI-TOF)calcdforC 32 H 29 O4[M+H] + :477.2060,found:477.2062.

[0077] Example 8: Preparation of Compound 4h

[0078]

[0079] 2-iodo-1-methyl-3-(prop-1-en-2-yl)benzene (51.6 mg, 0.2 mmol), 1,2-bis(4-methoxyphenyl)acetylene (95.2 mg, 0.4 mmol), (R)-2,8-dimethyl-2-((4R,8R)-4,8,12-trimethyltridecyl)chroman-6-ylcarboxylate (258 mg, 0.6 mmol), bis(acetonitrile)palladium dichloride (5.2 mg, 0.02 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (19.08 mg, 0.04 mmol) and potassium carbonate (82.4 mg, 0.6 mmol) were added to a 25 mL reaction bottle in sequence. Then 1.0 mL of ethylene glycol dimethyl ether was added, the mixture was sealed, and the mixture was stirred in an oil bath at 70° C. for 12 hours. After the reaction was complete, the solvent was removed by rotary evaporation and then separated by column chromatography (petroleum ether / ethyl acetate = 10:1-5:1, v / v) to obtain a light yellow liquid (69 mg, yield 44%).

[0080] 1 HNMR(400MHz, CDCl3)δ7.56-7.52(m,1H),7.39-7.35(m,1H),7.33-7.28(m,2H),7.26-7.23(m,2 H),7.19(d,J=8.4Hz,2H),6.83(d,J=8.3Hz,2H),6.77(d,J=8.3Hz,2H),6.07(dt,J=11.1,3.1Hz ,2H),3.77(d,J=9.3Hz,6H),3.05-2.90(m,2H),2.57(t,J=5.9Hz,2H),2.01(s,3H),1.56-1.46( m,6H),1.32-1.19(m,18H),1.15-1.11(m,2H),1.08-1.03(m,3H),0.85(dd,J=10.6,6.6Hz,12H). 13 C{ 1 H}NMR (101MHz, CDCl3) δ170.0,158.7,158.5,149.3,131.6,130.8,128.5,127. 2,125.6,122.8,121.1,120.8,120.7,119.0,113.7,113.6,76.1,55.2,53.4,4 1.8,40.3,39.5,37.6,37.54,37.53,37.4,32.9,32.8,28.1,24.9,24.6,24.4, 24.4,24.3,22.9,22.8,22.4,21.1,19.9,19.8,16.2.HRMS(ESI-TOF)calcdforC53 H 69 O5[M+H] + :785.5140,found:785.5143.

[0081] Example 9: Preparation of Compound 4i

[0082]

[0083] 2-iodo-1-methyl-3-(prop-1-en-2-yl)benzene (51.6 mg, 0.2 mmol), 1,2-bis(4-methoxyphenyl)acetylene (95.2 mg, 0.4 mmol), (E)-4-(3,5-dimethoxyphenylphenyl)formic acid phenyl ester (170.4 mg, 0.6 mmol), bis(acetonitrile)palladium dichloride (5.2 mg, 0.02 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (19.08 mg, 0.04 mmol) and potassium carbonate (82.4 mg, 0.6 mmol) were added to a 25 mL reaction bottle in sequence. Then 1.0 mL of ethylene glycol dimethyl ether was added, the mixture was sealed, and stirred in an oil bath at 80° C. for 12 hours. After the reaction was complete, the solvent was removed by rotary evaporation and then separated by column chromatography (petroleum ether / ethyl acetate = 10:1-5:1, v / v) to obtain a light yellow liquid (83 mg, yield 65%).

[0084] 1 HNMR(400MHz, CDCl3)δ7.57-7.53(m,1H),7.41-7.28(m,5H),7.27-7.22(m ,2H),7.21-7.14(m,2H),7.00-6.87(m,2H),6.85-6.80(m,2H),6.80-6.75 (m,2H),6.61(d,J=2.2Hz,2H),6.57-6.43(m,2H),6.37(t,J=2.2Hz,1H),3 .79(s,6H),3.77(s,3H),3.74(s,3H),3.03(q,J=13.6Hz,2H),1.55(s,3H). 13 C{ 1H}NMR(101MHz, CDCl3)δ169.1,161.0,158.7,158.5,150.0,149.4,149.1,143.9,139.3,134.8,131.5,130.7,128.8,128.3,128.3,127.4, 127.33,127.27,125.6,122.7,121.7,120.8,113.7,113.6,104.6,100.1,55.4,55.20,55.18,53.4,41.8,24.4.HRMS(ESI-TOF)calcdforC 42 H 39 O6[M+H] + :639.2741,found:639.2745.

[0085] Example 10: Preparation of Compound 4j

[0086]

[0087] To a 25 mL reaction bottle, 2-iodo-1-methyl-3-(prop-1-en-2-yl)benzene (51.6 mg, 0.2 mmol), 1,2-bis(4-methoxyphenyl)acetylene (95.2 mg, 0.4 mmol), (8S,9S,12R,14S)-12-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-3-ylcarboxylate (178.8 mg, 0.6 mmol), bis(acetonitrile)palladium dichloride (5.2 mg, 0.02 mmol), 2-dicyclohexylphospho-2',4',6'-triisopropylbiphenyl (19.08 mg, 0.04 mmol) and potassium carbonate (82.4 mg, 0.6 mmol) were added in sequence. Then, 1.0 ml of ethylene glycol dimethyl ether was added, the mixture was sealed, and stirred in an oil bath at 80°C for 16 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and then separated by column chromatography (petroleum ether / ethyl acetate = 10:1-5:1, v / v) to obtain a light yellow liquid (79 mg, yield 61%).

[0088] 1HNMR(400MHz, CDCl3)δ7.55(dd,J=6.2,2.1Hz,1H),7.39-7.35(m,1H),7.30(m,2H),7.26-7.22(m,2 H),7.21-7.14(m,2H),7.12(d,J=8.5Hz,1H),6.87-6.80(m,2H),6.77(d,J=8.4Hz,2H),6.30(dt,J=8 .5,3.1Hz,1H),6.22(t,J=2.8Hz,1H),3.77(d,J=9.5Hz,6H),3.13-2.89(m,2H),2.84-2.67(m,2H), 2.48(dd,J=18.9,8.6Hz,1H),2.37-2.26(m,1H),2.24-1.90(m,5H),1.59-1.31(m,9H),0.87(s,3H). 13 C{ 1 H}NMR(101MHz,CDCl3)δ169.5,158.7,158.5,149.5,149.2,148.4,144.0,13 9.4,137.9,137.2,131.6,130.8,128.4,127.31,127.25,126.3,125.6,122.7 ,121.6,120.7,118.7,113.7,113.6,55.21,53.4,50.4,48.0,44.2,41.8,38 .0,36.0,31.6,29.3,26.4,25.8,24.4,21.7,13.9.HRMS(ESI-TOF)calcdforC 44 H 45 O5[M+H] + :653.3262,found:653.3262.

[0089] Example 11: Preparation of Compound 4k

[0090]

[0091] 2-iodo-1-methyl-3-(prop-1-en-2-yl)benzene (51.6 mg, 0.2 mmol), 1,2-bis(4-methoxyphenyl)acetylene (95.2 mg, 0.4 mmol), 4-oxo-2-phenyl-4H-chromen-6-ylcarboxylate (159.6 mg, 0.6 mmol), bis(acetonitrile)palladium dichloride (5.2 mg, 0.02 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (19.08 mg, 0.04 mmol) and potassium carbonate (82.4 mg, 0.6 mmol) were added to a 25 mL reaction bottle in sequence, and then 1.0 mL of ethylene glycol dimethyl ether was added, the mixture was sealed, and the mixture was stirred in an oil bath at 77° C. for 16 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and then separated by column chromatography (petroleum ether / ethyl acetate = 10:1-5:1, v / v) to obtain a light yellow liquid (77 mg, yield 62%).

[0092] 1 HNMR(400MHz, CDCl3)δ7.91-7.85(m,2H),7.59-7.49(m,5H),7.43-7.32(m,4H),7.26-7.22(m,2H),7.21-7.14(m,2H),6.89 -6.83(m,2H),6.78(d,J=8.9Hz,3H),6.65(dd,J=9.0,2.8Hz,1H),3.80(s,3H),3.75(s,3H),3.14-2.97(m,2H),1.59(s,3H). 13 C{ 1 H}NMR (101MHz, CDCl3) δ177.8,169.0,163.6,158.8,158.6,153.7,149.3,148.9,139.6,131.8,131.7,131.5,130.7,129.2,127. 9,127.5,126.4,125.7,122.6,120.9,119.4,117.6,113.8,113.7,107.2,55.3,55.2,53.4,41.7,24.4.HRMS(ESI-TOF)calcdforC 41 H 33 O6[M+H] + :621.2272,found:621.2273.

[0093] 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 synthesizing an indenyl acetate compound, characterized in that: The reaction formula of the synthesis method is as follows: In the formula, R 1 is selected from alkyl, alkoxy, trifluoromethyl, cyano, acetyl or halogen; R 2 and R 3 is selected from aryl or alkyl; Ar is aryl; The synthesis steps are: using halogenated arylethylene, diaryl alkyne and formate as raw materials, reacting in an organic solvent under the joint action of a palladium catalyst, a ligand and a base, and obtaining an indenyl acetate compound through post-treatment after the reaction is completed.

2. The method for synthesizing indenyl acetate compounds according to claim 1, characterized in that: The specific steps of the synthesis method are: The first step is to add halogenated arylethylene, diaryl alkyne and formate into a reaction vessel, and then add palladium catalyst, ligand, base and organic solvent in sequence, and heat to 60-90° C. for reaction under stirring conditions for 8-16 hours; Step 2: Detect the progress of the reaction by thin layer chromatography, and terminate the reaction when there is no raw material in the reaction system; obtain indenyl acetate compounds through post-treatment.

3. The method for synthesizing indenyl acetate compounds according to claim 1 or 2, characterized in that: The palladium catalyst is one of palladium acetate, palladium chloride, palladium trifluoroacetate, bis(triphenylphosphine)palladium dichloride, allylpalladium chloride or bis(acetonitrile)palladium dichloride.

4. The method for synthesizing indenyl acetate compounds according to claim 1 or 2, characterized in that: The ligand is one of a bidentate phosphine ligand, a trialkylphosphine ligand or a triarylphosphine ligand derivative.

5. The method for synthesizing indenyl acetate compounds according to claim 1 or 2, characterized in that: The base is one of potassium acetate, cesium acetate, potassium carbonate, sodium acetate, cesium carbonate and potassium phosphate.

6. The method for synthesizing indenyl acetate compounds according to claim 1 or 2, characterized in that: The organic solvent is one of ethylene glycol dimethyl ether, toluene, dioxane, tetrahydrofuran or 1,2-dichloroethane.

7. The method for synthesizing indenyl acetate compounds according to claim 1 or 2, characterized in that: The halogenated aromatic vinyl is 1-iodine-2-(prop-1-en-2-yl)benzene, 1-iodine-4-methyl-2-(prop-1-en-2-yl)benzene, 4-fluoro-1-iodine-2-(prop-1-en-2-yl)benzene, 4-chloro-1-iodine-2-(prop-1-en-2-yl)benzene, 1-iodine-2-(prop-1-en-2-yl)-4-(trifluoromethyl)benzene, 2-iodine-4-methoxy-1-(prop-1-en-2-yl)benzene, 4-chloro-2-iodine-1-(prop-1-en-2-yl)benzene, 4-fluoro-2-iodine-1-(prop-1-en-2-yl)benzene, 2-iodine-1-methyl-3-(prop-1-en-2-yl)benzene, 1-(but-1-en-2-yl)- 2-iodobenzene, 1-(hex-1-en-2-yl)-2-iodobenzene; the diaryl alkyne is 1,2-diphenylacetylene, 1,2-di-p-tolueneacetylene, 1,2-bis(4-(tert-butyl)phenyl)acetylene, 1,2-bis(4-methoxyphenyl)acetylene, 1,2-bis(3-fluorophenyl)acetylene, 1,2-bis(3-chlorophenyl)acetylene, 1,2-bis(3-methoxyphenyl)acetylene, etc.; the formic acid ester is one of phenyl formate, p-tolyl formate, p-methoxyphenyl formate, 4-fluorophenyl formate, 4-chlorophenyl formate, 3-fluorophenyl formate, 3-chlorophenyl formate, 3-methoxyphenyl formate, 3-methylphenyl formate, 2-methylphenyl formate, and 2-methoxyphenyl formate.

8. The method for synthesizing indenyl acetate compounds according to claim 1 or 2, characterized in that: The molar ratio of the halogenated arylethylene, diaryl alkyne, formate, palladium catalyst, ligand and base is 0.1:0.2:0.3:0.01:0.02:0.3; the concentration of the halogenated arylethylene in the reaction solution is 0.2 mol / L.

9. The method for synthesizing indenyl acetate compounds according to claim 1 or 2, characterized in that: The post-treatment steps are as follows: after the reaction is finished, the reaction system is cooled, the organic solvent is removed by rotary evaporation under reduced pressure, and the mixture is concentrated, the residue is mixed with silica gel and separated by column chromatography to obtain indenyl acetate compounds.

10. The method for synthesizing indenyl acetate compounds according to claim 9, characterized in that: The eluent of the column chromatography is a mixture of petroleum ether and ethyl acetate in a volume ratio of 20:1 to 5:1.

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