CN111217654A - Palladium-catalyzed meta-arylation reaction and application thereof in synthesis of vemurafenib analogue - Google Patents
Palladium-catalyzed meta-arylation reaction and application thereof in synthesis of vemurafenib analogue Download PDFInfo
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Abstract
The invention relates to a palladium-catalyzed meta-arylation reaction and application thereof in synthesis of a vemurafenib analogue, which overcome the problems that byproducts are introduced in the reaction in the prior art, direct synthesis cannot be realized, and the production cost is high, realize direct C-H activation conversion of transition metal catalysis, and have the advantages of controllability, accuracy, high efficiency, no need of inert gas protection in the synthesis process, simple operation, low production cost and little environmental pollution. The technical scheme adopted by the invention is as follows: taking 0.25mmol of aromatic ring compound as a substrate, taking 10 mol% palladium acetate as a catalyst, taking 1-1.5 equivalents of norbornene as a medium, adding 3equiv of additive, adding 5-10 mol% of ligand, 1mL of benzotrifluoride and dichloroethane as a medium, coupling with 0.38mmol of aryl halide, and reacting at 80-120 ℃ for 12-24 h to obtain the 5-iodo-7-azaindole as a 5-position arylation product.
Description
The technical field is as follows:
the invention relates to a method for activating and converting meta-C-H, in particular to a palladium-catalyzed meta-arylation reaction and application thereof in synthesis of a vemurafenib analogue.
Background art:
control of regioselectivity is a key issue for transition metal catalyzed C — H functionalization. When the substrate molecule contains multiple C-H, it is important to control the reaction site. There have been many examples of successful ortho-directed C-H functionalization catalyzed by transition metals Pd (II), Rh (III), Ru (II), Ir (III), etc. [ T.W. Lyons, et.al.chem.Rev.2010,110,1147], whereas relatively few transition metal-catalyzed meta C-H functionalisations have been reported. The mechanism can be roughly divided into three types: substrate control, catalyst control, and other factors. (1) Substrate control includes controlling the reaction to occur in the meta position using steric hindrance, electronic effects [ c.cheng, et al. science 2014,343,853] or a Directing Group (DG) of the substrate. Typical representatives of this strategy are the complement right and the pioti design of U-type template directing groups that pioneering the meta and para C-H activation of arenes [ D.Leow, et.al.Nature, 2012,486,518], other directing group strategies including meta C-H activation of carboxylic acids as traceless directing groups [ M.Font, et.al.chem.Commun.2017, 53,5584] and norbornene (norbomene: NBE) as transient directing groups [ X. -C.Wang, et.al.Nature 2015,519,334 ]. (2) Catalyst control includes Cu [ r.j.phipps, et.al.science 2009,323,1593] and Ru [ o.saidi, et.al.j.am.chem.soc.2011,133,19298] transition metal catalysts and sterically bulky ligand controlled meta C-H functionalization. (3) Other factors include Ir catalyzed meta-boronation as facilitated by hydrogen bonding between the substrate and the catalyst.
Inspired by the native and ortho tandem coupling reactions of aryl iodides cooperatively catalyzed by Pd and norbornene reported by Catellani et al [ m.catellani, et al.angelw.chem.int.ed.engl.1997, 36,119 ], recently, the combination of C-H bond activation promoted by a targeting group and Catellani reaction successfully achieved functionalization of C-H in the meta-position of aromatics. The problem group of Dongbin reported that arylation reaction of meta-position of aromatic hydrocarbon mediated by norbornene with tertiary amine as a directing group [ Z.Dong, et.al.J.am. chem.Soc.2015,137,5887 ]. The authors found that the "acetic acid cocktail" can significantly increase the reaction rate, acetic acid can dissociate the coordination of the directing group and Pd by protonation, acetate ions contribute to the deprotonation metallization process, both additions contribute to the insertion of olefins, and the pyridine 3-arylation product is obtained in good yield; ligands play a key role in this approach because they act synergistically with many targeting groups to promote C-H activation, yet avoid some potential side reactions. The project group of the remaining gold rights obtains good application in the arylation of indole and pyridine meta-position by optimizing the multifunctional ligand 3-acetamido-2-hydroxypyridine and utilizing norbornene as a transient medium [ P.Wang, et.al.J.am.chem.Soc.2016, 138,9269 ]
The 7-azaindole is used as a key member in an azaindole family, the skeleton of the 7-azaindole is widely present in core structural units of active natural products and drug molecules, and researches show that the compounds have important biological activities such as cancer resistance, antibiosis, diabetes resistance and the like, so that the pharmaceutical chemistry family usually uses the compounds containing the 7-azaindole skeleton as lead compounds to carry out structural modification and modification on the compounds, and searches for drugs with more ideal curative effects by analyzing the structure-activity relationship with targets.
The invention further improves and optimizes the rest reported meta-position arylation reaction [ P.Wang, et.al.J.am.chem.Soc. 2016,138,9269 ], adopts new ligands and solvents to realize the meta-position arylation reaction, and applies the method to 7-azaindole to realize the synthesis of the Verofinib analogue by a brand new method.
The invention content is as follows:
the invention aims to provide a palladium-catalyzed meta-position arylation reaction and application thereof in synthesis of a vemurafenib analogue, which overcome the problems that byproducts can be introduced in the reaction in the prior art, direct synthesis cannot be realized, and the production cost is high, realize direct C-H activation conversion of transition metal catalysis, and have the advantages of controllability, accuracy, high efficiency, no need of inert gas protection in the synthesis process, simple operation, low production cost and small environmental pollution.
In order to achieve the purpose, the invention adopts the technical scheme that:
a palladium-catalyzed meta-arylation reaction and application thereof in synthesis of a vemurafenib analogue are characterized in that: taking 0.25mmol of aromatic ring compound as a substrate, taking 10 mol% palladium acetate as a catalyst, taking 1-1.5 equivalents of norbornene as a medium, adding 3equiv of additive, adding 5-10 mol% of ligand, 1mL of benzotrifluoride and dichloroethane as a medium, coupling with 0.38mmol of aryl halide, and reacting at 80-120 ℃ for 12-24 h to obtain the 5-iodo-7-azaindole as a 5-position arylation product.
The aromatic ring compound comprises acetamido-substituted aromatic hydrocarbon.
Aryl halides include iodobenzene, 4-methyl iodobenzene, 4-trifluoromethyl iodobenzene, 4-methoxy-iodobenzene, N-p-methylbenzenesulfonyl 5-iodoindole, 5-iodo-7 azaindole or 3-acyl-5-iodo-7-azaindole.
The norbornenes include norbornene or 2-oxycarbonyl norbornene.
The ligand is pyranoquinoline, pyridine, pyridone or quinoline.
The solvent is chlorobenzene, dichloroethane, toluene, DMSO, acetonitrile or DCE.
The additive is silver trifluoromethanesulfonate, silver acetate or silver carbonate.
The method for preparing the aromatic ring-based tandem C-H activation synthesis of the vemurafenib analogue by using the 7-azaindole 5-position arylation product 5-iodo-7-azaindole is characterized in that: the subsequent treatment process comprises the following steps: accurately weighing 0.25mmol of the prepared 5-iodo-7-azaindole, 0.38mmol of N- (3-5-difluoro-4-formylphenyl) propyl-1-sulfonamide, 3equiv of potassium carbonate and methanol in sequence at room temperature; and sequentially adding the measured reactants into a 25mL pressure-resistant pipe filled with magnetons, sealing the pressure-resistant pipe, stirring on a magnetic stirrer at room temperature, slowly heating to 108 ℃, and monitoring the reaction process by using thin-layer chromatography. Stopping the reaction after 12 hours under the pressure of 0.1MPa, cooling to room temperature, removing redundant solvent by using a rotary evaporator, separating residues by using column chromatography, and purifying and separating products by using 300-400-mesh silica gel as a stationary phase and using mixed solvents of ethyl acetate and petroleum ether in different proportions as eluents.
Compared with the prior art, the invention has the following advantages and effects:
1. the invention introduces guide groups (acetyl and amido) into a substrate, and realizes the arylation reaction with 7-azaindole through the activation of serial C-H bonds catalyzed by Pd under the action of transient medium of norbornene to construct the core skeleton of a drug molecule.
2. Meanwhile, on the premise of the prepared core framework, Vemurafenib analogue is synthesized by series C-H activation for the first time; the reaction process can be carried out in an air atmosphere without inert gas protection, and the synthesis process is simple to operate; shortening the reaction steps and having great potential application prospect.
3. After the reaction, the intermediate is further structurally modified, so that the high-efficiency synthesis of the drug and the drug-like molecules is realized, and more potential antitumor drugs can be screened out. Provides diversification and huge cost advantage for drug design and implementation, and enriches drug compound libraries.
The specific implementation mode is as follows:
in order to further understand the present invention, the following examples are further illustrated, which are only used for explaining the present invention and are not to be construed as limiting the scope of the present invention.
Aromatic hydrocarbons are used as a substrate, palladium acetate is used as a catalyst, norbornene is used as a medium, pyridone is used as a ligand (5 mol% -20 mol%) norbornene (1equiv-1.5equiv) is used as a medium, silver acetate is used as an additive, the aromatic hydrocarbons and aryl halides are coupled, the reaction is carried out for 12-24 hours at the temperature of 80-120 ℃, and a 7-azaindole 5-position arylation product is obtained through subsequent treatment.
The reaction equation is as follows:
specific examples are as follows.
Example 1
Accurately weighing acetylamino-substituted aromatic hydrocarbon (0.25mmol,0.25mmol88mg), 4-methyl iodobenzene (0.38mmol,0.38mmol83mg), pyranoquinoline (10 mol%, 10 mol% 5g), palladium acetate (10 mol%, 6g), (10 mol%), silver acetate (3equiv,3equiv 125g), 2-oxycarbonyl norbornene (1.5equiv,)1.5equiv and trifluorotoluene (2.0mL) in this order at room temperature; and sequentially adding the measured reactants into a 25mL pressure-resistant pipe filled with magnetons, sealing the pressure-resistant pipe, stirring on a magnetic stirrer at room temperature, slowly heating to 90 ℃, and monitoring the reaction process by using thin-layer chromatography. The reaction was stopped after 20h at 0.1MPa, cooled to room temperature, the mixture was extracted with diethyl ether (10 mL. times.3), the organic phases were combined, excess solvent was removed by rotary evaporator, the residue was chromatographed using column chromatography, the product was purified using 300 mesh silica gel as the stationary phase and a mixed solvent of ethyl acetate and petroleum ether in different proportions as the eluent.
The physical properties and characterization data of the obtained compounds are as follows:
white solid:1H NMR(500MHz,acetone-d6)δ9.55(br,1H,N-H),7.63 (d,J＝2.0Hz,1H),7.54(d,J＝8.0Hz,2H),7.47(dd,J＝7.5,1.8Hz, 1H),7.33(m,1H),7.28(d,J＝8.5Hz,1H),7.26(d,J＝8.5Hz,2H), 3.98(s,2H),2.35(s,3H).
13C NMR(125MHz,acetone-d6)δ169.59,139.62,138.63,137.62,136.92, 135.21,134.82,131.63,130.32,129.51,127.34,126.31,41.42,19.30.
example 2
Accurately weighing, in order, acetamido-substituted aromatic hydrocarbon (0.25mmol,0.25mmol88mg), 4-trifluoromethyl iodobenzene (0.38mmol,0.38mmol103mg), pyranoquinoline (10 mol% ), palladium acetate (10 mol%, 10 mol% 6g), silver triflate (3equiv,3equiv193g), 2-oxycarbonyl norbornene (1.5equiv,) and chlorobenzene (2.0mL) at room temperature; and sequentially adding the measured reactants into a 25mL pressure-resistant pipe filled with magnetons, sealing the pressure-resistant pipe, stirring on a magnetic stirrer at room temperature, slowly heating to 110 ℃, and monitoring the reaction process by using thin-layer chromatography. Stopping the reaction after 22h under 0.1MPa, cooling to room temperature, extracting the mixture with diethyl ether (10mL multiplied by 3), combining organic phases, removing excessive solvent by using a rotary evaporator, separating residues by using column chromatography, and purifying and separating the product by using 300-400 mesh silica gel as a stationary phase and using a mixed solvent of ethyl acetate and petroleum ether in different proportions as an eluent.
The physical properties and characterization data of the obtained compounds are as follows:
brown solid:1H NMR(500MHz,acetone-d6)δ9.59(br,1H,N-H),7.88 (d,J＝8.0Hz,2H),7.79(d,J＝8.2Hz,2H),7.73(d,J＝1.5Hz,1H), 7.58(dd,J＝8.0,2.0Hz,1H),7.43(m,3H),7.36(d,J＝7.5Hz,1H), 4.03(s,2H).
13C NMR(125MHz,acetone-d6)δ169.43,145.42,138.60,137.98,135.28, 131.89,130.05,129.43(q,J＝32Hz),128.13,126.83,126.58(q,J＝ 4.0Hz),125.51(q,J＝270Hz),41.28.
19F NMR(376MHz,acetone-d6)δ-56.02(t,J＝21Hz,3F),-62.11(s, 3F),-143.61--143.25(m,4F).
example 3
Acetylamino-substituted aromatic hydrocarbon (0.25mmol,0.25mmol88mg), N-p-toluenesulfonyl-5-iodoindole (0.38mmol,0.38mmol151mg), pyranoquinoline (10 mol%, 10 mol% 5g), palladium acetate (10 mol%, 10 mol% 6g), silver carbonate (3equiv,3equiv207g), norbornene (3equiv,3equiv71g) and dichloroethane (2.0mL) were accurately weighed in this order at room temperature, and the progress of the reaction was monitored by thin layer chromatography. The reaction was stopped after 15h at 0.1MPa, cooled to room temperature, the mixture was extracted with diethyl ether (10 mL. times.3), the organic phases were combined, excess solvent was removed by rotary evaporator, the residue was chromatographed using column chromatography, the product was purified using 400 mesh silica gel as the stationary phase and a mixed solvent of ethyl acetate and petroleum ether in different proportions as the eluent.
The physical properties and characterization data of the obtained compounds are as follows:
white solid:1H NMR(500MHz,acetone-d6)δ9.54(br,1H,N-H),8.07 (d,J＝8.5Hz,1H),7.89(d,J＝8.0Hz,2H),7.83(d,J＝1.0Hz,1H), 7.73(d,J＝3.5Hz,1H),7.64(d,J＝1.0Hz,1H),7.63(dd,J＝8.8, 1.2Hz,1H),7.54(m,1H),7.49(dd,J＝7.5,1.5Hz,1H),7.37(d,J ＝8.0Hz,2H),7.29(d,J＝7.5Hz,1H),6.84(d,J＝4.0Hz,1H),3.99 (s,2H),2.40(s,3H).
13C NMR(125MHz,acetone-d6)δ169.52,146.44,139.71,137.26,137.03, 136.05,135.02,134.88,132.56,131.68,130.95,130.04,128.23,127.76, 126.76,124.58,120.35,114.59,110.36,41.42,21.41.
example 4
Acetylamino-substituted aromatic hydrocarbon (0.25mmol,0.25mmol88mg), 5-iodo-7-azaindole (0.38mmol,0.38mmol92mg), pyranoquinoline (10 mol%, 10 mol% 5g), palladium acetate (10 mol%, 10 mol% 6g), silver carbonate (3equiv,3equiv207g), norbornene (3equiv,71g3equiv) and dichloroethane (2.0mL) were accurately weighed in this order at room temperature, and the progress of the reaction was monitored by thin layer chromatography. The reaction was stopped after 15h at 0.1MPa, cooled to room temperature, the mixture was extracted with diethyl ether (10 mL. times.3), the organic phases were combined, excess solvent was removed by rotary evaporator, the residue was chromatographed using column chromatography, the product was purified using 300 mesh silica gel as the stationary phase and a mixed solvent of ethyl acetate and petroleum ether in different proportions as the eluent.
The physical properties and characterization data of the obtained compounds are as follows:
white solid:1H NMR(500MHz,acetone-d6)δ12.51(br,1H,N-H),9.54 (br,1H,N-H),8.07(s,1H),7.83(d,J＝1.0Hz,1H),7.73(d,J＝3.5 Hz,1H),7.64(d,J＝1.0Hz,1H),7.63(m,1H),7.54(m,1H),7.49(dd, J＝7.5,1.5Hz,1H),6.84(d,J＝4.0Hz,1H),3.99(s,2H).
13C NMR(125MHz,acetone-d6)δ169.52,146.44,139.71,137.26,136.05, 135.02,134.88,132.56,131.68,130.04,127.76,126.76,124.58,114.59, 110.36,41.42.
example 5
Acetylamino-substituted aromatic hydrocarbon (0.25mmol,88mg0.25mmol), 3-acyl-5-iodo-7-azaindole (0.38mmol, 197mg mmol), pyranoquinoline (10 mol%, 10 mol% 5g), palladium acetate (10 mol%, 10 mol% 6g), silver carbonate (3equiv,3equiv207g), norbornene (3equiv,71g, 3equiv), and dichloroethane (2.0mL) were accurately weighed in this order at room temperature, and the progress of the reaction was monitored by thin layer chromatography. Stopping the reaction after 15h under 0.1MPa, cooling to room temperature, extracting the mixture with diethyl ether (10mL multiplied by 3), combining organic phases, removing excessive solvent by using a rotary evaporator, separating residues by using column chromatography, and purifying and separating the product by using 300-400 mesh silica gel as a stationary phase and using a mixed solvent of ethyl acetate and petroleum ether in different proportions as an eluent.
The physical properties and characterization data of the obtained Vemurafenib analogues are as follows:
white solid:1H NMR(500MHz,acetone-d6)δ12.54(br,1H,N-H),9.54 (br,1H,N-H),8.07(d,J＝8.5Hz,1H),7.89(d,J＝8.0Hz,2H),7.83 (d,J＝1.0Hz,1H),7.73(d,J＝3.5Hz,1H),7.64(d,J＝1.0Hz,1H), 7.63(dd,J＝8.8,1.2Hz,1H),7.54(m,1H),7.49(dd,J＝7.5,1.5Hz, 1H),7.37(d,J＝8.0Hz,2H),7.29(d,J＝7.5Hz,1H),7.04(m,1H), 7.01(m,1H),3.99(s,2H),3.10(t,J＝2.4,2H),1.87(m,2H),1.21(t, J＝2.4,2H).
13C NMR(125MHz,acetone-d6)δ196.24,169.52,152.03,151.81,146.44, 139.71,137.26,137.03,136.05,135.02,134.88,132.56,131.68,130.95, 130.04,129.65,128.23,127.76,126.76,124.58,123.63,120.35,114.59, 112.31,110.36,62.31,41.42,21.41,19.68,14.32.
the application of the products of the above examples to a process for preparing vemurafenib analogs is illustrated by the following two examples:
example 6
Accurately weighing the above prepared 5-iodo-7-azaindole (0.25mmol, 61mg), N- (3-5-difluoro-4-formylphenyl) propyl-1-sulfonamide (0.38mmol, 100mg), potassium carbonate (3equiv,3equiv104g), and methanol (1.0ml) in this order at room temperature; and sequentially adding the measured reactants into a 25mL pressure-resistant pipe filled with magnetons, sealing the pressure-resistant pipe, stirring on a magnetic stirrer at room temperature, slowly heating to 108 ℃, and monitoring the reaction process by using thin-layer chromatography. Stopping the reaction after 12 hours under the pressure of 0.1MPa, cooling to room temperature, removing redundant solvent by using a rotary evaporator, separating residues by using column chromatography, and purifying and separating products by using 300-400-mesh silica gel as a stationary phase and using mixed solvents of ethyl acetate and petroleum ether in different proportions as eluents.
The physical properties and characterization data of the obtained compounds are as follows:
yellow solid: 1H NMR (400MHz, CDCl)3):δ＝12.53(s,1H),8.62(dd,J ＝7.4Hz,J＝1.6Hz,1H),8.13(td,J＝8.6Hz,J＝2.6Hz,1H),7.33 (dd,J＝7.9Hz,J＝1.6Hz,1H),6.83(dd,J＝7.6Hz,J＝1.8Hz,1H), 6.73(dd,J＝7.8Hz,J＝1.9Hz,1H),6.53(m,1H),6.16(s,1H),3.10 (t,J＝4.6Hz,2H),1.69(m,2H),0.97(t,J＝4.6Hz,3H)ppm；
HRMS(APCI):[M+H]+(C17H16N3O2SI):calcd m/z 506.9925,found:506.9926。
Example 7
Accurately weighing 3-hydroxy 5-iodo-7-azaindole (0.25mmol, 122mg), dichlorodicyanobenzoquinone (0.5mmol, 114mg), and dioxane (1.0ml) at room temperature; and sequentially adding the measured reactants into a 25mL pressure-resistant pipe filled with magnetons, sealing the pressure-resistant pipe, stirring on a magnetic stirrer at room temperature, slowly heating to 100 ℃, and monitoring the reaction process by using thin-layer chromatography. Stopping the reaction after 12 hours under the pressure of 0.1MPa, cooling to room temperature, removing redundant solvent by using a rotary evaporator, separating residues by using column chromatography, and purifying and separating products by using 300-400-mesh silica gel as a stationary phase and using mixed solvents of ethyl acetate and petroleum ether in different proportions as eluents.
The physical properties and characterization data of the obtained compounds are as follows:
yellow solid: 1H NMR (400MHz, CDCl)3):δ＝12.53(s,1H),8.68(dd,J ＝7.6Hz,J＝1.6Hz,1H),8.18(td,J＝8.6Hz,J＝2.6Hz,1H),7.35(dd, J＝7.9Hz,J＝1.6Hz,1H),6.83(dd,J＝7.6Hz,J＝1.8Hz,1H),6.73 (dd,J＝7.8Hz,J＝1.9Hz,1H),6.53(m,1H),3.15(t,J＝4.6Hz,2H), 1.89(m,2H),1.27(t,J＝4.6Hz,3H)ppm；
HRMS(APCI):[M+H]+(C17H14F2N3O3SI):calcd m/z 504.9769,found: 504.9768。
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, modifications and decorations can be made without departing from the core technology of the present invention, and the modifications and decorations shall also fall within the scope of the patent protection of the present invention. Any changes which come within the meaning and range of equivalency of the claims are to be embraced within their scope.
Claims (8)
1. A palladium-catalyzed meta-arylation reaction and application thereof in synthesis of a vemurafenib analogue are characterized in that: taking 0.25mmol of aromatic ring compound as a substrate, taking 10 mol% palladium acetate as a catalyst, taking 1-1.5 equivalents of norbornene as a medium, adding 3equiv of additive, adding 5-10 mol% of ligand, 1mL of benzotrifluoride and dichloroethane as a medium, coupling with 0.38mmol of aryl halide, and reacting at 80-120 ℃ for 12-24 h to obtain the 5-iodo-7-azaindole as a 5-position arylation product.
2. The palladium-catalyzed meta-arylation reaction of claim 1 and use in the synthesis of vemurafenib analogs, wherein: the aromatic ring compound comprises acetamido-substituted aromatic hydrocarbon.
3. The palladium-catalyzed meta-arylation reaction of claim 1 or 2 and use in the synthesis of vemurafenib analogs, wherein: aryl halides include iodobenzene, 4-methyl iodobenzene, 4-trifluoromethyl iodobenzene, 4-methoxy-iodobenzene, N-p-methylbenzenesulfonyl 5-iodoindole, 5-iodo-7 azaindole or 3-acyl-5-iodo-7-azaindole.
4. The palladium-catalyzed meta-arylation reaction of claim 3 and use in the synthesis of vemurafenib analogs, wherein: the norbornenes include norbornene or 2-oxycarbonyl norbornene.
5. The palladium-catalyzed meta-arylation reaction of claim 4 and use in the synthesis of vemurafenib analogs, wherein: the ligand is pyranoquinoline, pyridine, pyridone or quinoline.
6. The palladium-catalyzed meta-arylation reaction of claim 5 and use in the synthesis of vemurafenib analogs, wherein: the solvent is chlorobenzene, dichloroethane, toluene, DMSO, acetonitrile or DCE.
7. The palladium-catalyzed meta-arylation reaction of claim 6, and the use thereof in the synthesis of vemurafenib analogs, wherein: the additive is silver trifluoromethanesulfonate, silver acetate or silver carbonate.
8. The method for preparing the aromatic ring-based tandem C-H activation synthesis of the vemurafenib analog from the 5-position arylation product 5-iodo-7-azaindole according to claim 1, wherein: the subsequent treatment process comprises the following steps: accurately weighing 0.25mmol of the prepared 5-iodo-7-azaindole, 0.38mmol of N- (3-5-difluoro-4-formylphenyl) propyl-1-sulfonamide, 3equiv of potassium carbonate and methanol in sequence at room temperature; and sequentially adding the measured reactants into a 25mL pressure-resistant pipe filled with magnetons, sealing the pressure-resistant pipe, stirring on a magnetic stirrer at room temperature, slowly heating to 108 ℃, and monitoring the reaction process by using thin-layer chromatography. Stopping the reaction after 12 hours under the pressure of 0.1MPa, cooling to room temperature, removing redundant solvent by using a rotary evaporator, separating residues by using column chromatography, and purifying and separating products by using 300-400-mesh silica gel as a stationary phase and using mixed solvents of ethyl acetate and petroleum ether in different proportions as eluents.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN114956924A (en) * | 2022-06-29 | 2022-08-30 | 河南科技学院 | Method for synthesizing polyfluoro biaryl through series/coupling reaction |
| CN114956924B (en) * | 2022-06-29 | 2024-01-30 | 河南科技学院 | Method for synthesizing polyfluorinated biaryl through series connection/coupling reaction |
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