Organic base participated benzofuran preparation method

Abstract

The invention provides an organic alkali participated benzofuran preparation method, which comprises that a brominated compound (1) represented by a formula 1 is subjected to a reaction in the presence of a catalyst to generate a benzofuran-3 (2H)-ketone compound, and has the following beneficial effects: the route of the patent avoids toxic reagents, has high bromine atom region selection, and has a good application prospect in the preparation of benzofuran-3 (2H)-ketone compounds. Cyclization is carried out among molecules, so that the atom economy is good; only a one-step synthesis process is adopted, raw materials are simple and easy to obtain, the product yield is high, operation is easy and convenient, broad-spectrum substrate applicability is achieved, and the method is suitable for industrial production.

Description

Technical Field

[0001] This invention belongs to the field of chemical synthesis technology of natural products, and specifically relates to a method for preparing benzofuran involving an organic base. Background Technology

[0002] Benzofuran-3(2H)-one is an oxygen-containing heterocyclic compound and a key intermediate in the synthesis of orange ketone compounds, widely distributed in nature. It is also a key structural motif in several important natural bioactive compounds, possessing a variety of important pharmacological activities. For example, Applanatumin A, a novel terpenoid dimer isolated from the fungus *Ganoderma applanatum*, exhibits potent anti-fibrotic activity against TGF-β1-induced human renal proximal tubular cells. Sch202596, isolated from cultures of the fungus *Aspergillus* sp., has been shown to be the first non-peptide antagonist of the gallanapeptide receptor subtype GalR1, and holds promise for treating eating disorders such as overeating and obesity. Linobiflavonoid possesses significant anticancer activity; although its inhibitory effect on cancer cell lines is weaker than that of paclitaxel, it exhibits lower toxicity to Vero cells. Additionally, Griseofulvin, a spirocyclic benzofuran-3(2H)-one derivative, was first isolated from filamentous fungi in 1939 and has long been considered an antifungal drug. Prior to terbinafine's approval by the U.S. Food and Drug Administration in 2007, this compound was the only treatment for tinea capitis. Furthermore, benzofuran-3(2H)-one derivatives are suitable leads for the development of selective monoamine oxidase inhibitors, potentially for the treatment of diseases such as Parkinson's disease and Alzheimer's disease.

[0003] Besides its potential medicinal value, benzofuran-3(2H)-one possesses a unique molecular framework, making it a highly versatile and crucial synthetic intermediate. It plays a vital role in total synthesis, enabling the synthesis of various biologically active compounds, such as BKCa channel openers, phainanoid A, heliquinomycin analogs, and orange ketones. Therefore, the wide range of applications of benzofuran-3(2H)-one and its derivatives has sparked considerable interest among synthetic chemists. In-depth research into the properties and applications of these compounds can advance scientific development in the fields of biomedicine and organic synthesis, providing crucial support for the discovery and synthesis of new drugs.

[0004] The commonly used methods for synthesizing benzofuran-3(2H)-ketone compounds include the following:

[0005] In 1942, Shriner's group reported the synthesis of benzofuran compounds. They synthesized 2,4,6-trihydroxyphenylchloromethyl ketone imine hydrochloride via a Hoesch reaction between resorcinol and chloroacetonitrile. This compound was then hydrolyzed to 2,4,6-trihydroxy-α-chloroacetophenone. Finally, treatment with sodium acetate resulted in ring closure, yielding the target compound, 4,6-dihydroxycoumarin-3-one. This cyclization method required three steps to generate the target compound, was time-consuming, and used the toxic compound chloroacetonitrile.

[0006]

[0007] In 2004, Subbaraju's group reported on the synthesis of benzofurans. They used pyrogallol and chloroacetic acid in the presence of BF3 diethyl ether via a Friedal-Crafts reaction to obtain a chlorinated compound 3, which was then cyclized under reflux for 6 hours with sodium acetate as the base and ethanol as the solvent, yielding 6,7-dihydroxycoumarone in 85% yield. This method uses chloroacetic acid, which is highly toxic to aquatic organisms, and also uses boron trifluoride diethyl ether, a reagent with a strong, unpleasant odor. Overall, this method has a long reaction time and low yield.

[0008]

[0009] In 2010, Go's research group reported the synthesis of benzofurans. Using o-hydroxyacetophenone as the starting material, copper bromide was added to a mixture of ethyl acetate and chloroform and refluxed for 8 hours to induce bromination at the α-position of the ketone. Subsequently, a cyclization closure reaction was carried out in a KOH and MeOH system. The overall yield was 21–55%, which was relatively low and the reaction time was long.

[0010]

[0011] In 2017, Wang's research group reported the synthesis of unsubstituted benzofuran compounds. The group first brominated the starting compound, and then cyclized the brominated product under the reaction conditions of triethylamine and acetonitrile. This route has mild reaction conditions, but the reaction time is relatively long.

[0012]

[0013] In 2010, Yang's research group also reported on the synthesis of benzofuran. They first brominated the starting compound using copper bromide as the bromine source in an ethyl acetate / chloroform system, and then cyclized the brominated compound under KF and DMF conditions. This reaction could be carried out at room temperature, but the reaction time was long, and the use of DMF as the reaction solvent made it difficult to remove during post-reaction processing, posing significant challenges to the purification of the reaction.

[0014]

[0015] In 2012, the Vovk group also reported the synthesis of benzofuran (Ukrainica Bioorganica Acta, 2021, 16(2):12-17; https: / / doi.org / 10.15407 / bioorganica2021.02.012). Phenyl chloroacetate was generated by reacting phenol with chloroacetyl chloride, and then further converted to o-hydroxy-α-haloacetophenone with varying success rates under Fries rearrangement conditions using aluminum trichloride. Subsequently, a cyclization reaction was carried out under conditions of sodium acetate hydrate and methanol to generate benzofuran-3(2H)-ketone compounds with an overall yield of 16%. This reaction involved three steps and the yield was relatively low.

[0016]

[0017] It is evident that current methods for synthesizing benzofuran mostly suffer from low yields, use highly toxic reagents which are not environmentally friendly, have long reaction times, require harsh reaction conditions, or use solvents that are difficult to remove. In short, they fail to meet practical application needs. Therefore, obtaining a preparation method with mild reaction conditions, a simple preparation route, high yield, and environmental friendliness is an urgent technical problem to be solved in this field. Summary of the Invention

[0018] To address the shortcomings of existing technologies, the present invention adopts the following technical solution:

[0019] The first aspect of this invention provides a method for preparing benzofuran involving an organic base, comprising the following steps:

[0020] The brominated compound (1) shown in Formula 1 is reacted with a catalyst to generate benzofuran-3(2H)-ketone compounds, as shown in Formula I:

[0021]

[0022] in,

[0023] R1 is selected from H, Any one or more of them;

[0024] R6 is selected from any one or more of F, Br, and I;

[0025] R2 is selected from any one or more of H and Br;

[0026] R3 is selected from any one or more of H, CH3O-, -OH, -OAc, F, and -OBn;

[0027] R4 is selected from any one or more of H, CH3O-, -OH, -OAc, -NO2, -CN, F, Cl, Br, and -TBSOMe;

[0028] R5 is selected from any one or more of H, CH3O-, -OH, and -OAc;

[0029] Alternatively, R2 and R3 can form a ring, i.e., the structure of Equation 1 is...

[0030] Furthermore, the catalyst for the reaction is N,N-diisopropylethylamine;

[0031] Furthermore, the reaction solvent is acetonitrile;

[0032] Furthermore, the ratio of the compound of Formula 1 to the catalyst reaction equivalence is 1:1 to 3; further, the ratio of the compound of Formula 1 to the catalyst reaction equivalence is 1:2;

[0033] Furthermore, the reaction is carried out at room temperature;

[0034] Furthermore, the compound of Formula 1 is selected from any one or more of the following compounds:

[0035]

[0036] Furthermore, the compound of formula 2 is selected from any one or more of the following compounds:

[0037]

[0038] The invention has the following beneficial effects:

[0039] (1) Green reaction system: This patented route uses the reaction system of N,N-diisopropylethylamine and acetonitrile, avoiding the use of toxic reagents (chloroacetonitrile, boron trifluoride ether, etc.);

[0040] (2) High atom economy: Bromine atoms have high regioselectivity and undergo intermolecular cyclization, resulting in good atom economy;

[0041] (3) Short route and high yield: This invention uses only one-step synthesis process, the raw materials are simple and readily available, the product yield is high (≥80%), and the operation is simple (the reaction can be carried out at room temperature and pressure).

[0042] (4) Industrialization potential: The yield in gram-scale experiments (10 mmol) remains >95%, and the solvent (CH3CN) can be recovered by distillation.

[0043] (5) Broad substrate applicability: This patent is compatible with various functional groups (e.g., -OAc, -OH, -NO2-F, -Cl, -OCH3) and has a high yield. At the same time, this method is also applicable to the cyclization of chloroacetophenone. Attached Figure Description

[0044] Figure 1 For compound 2-1 1 H NMR (400MHz CDCl3)

[0045] Figure 2 For compound 2-1 13 C NMR (100MHz CDCl3)

[0046] Figure 3 For compound 2-2 1 H NMR (400MHz CDCl3)

[0047] Figure 4 For compound 2-2 13 C NMR (100MHz CDCl3)

[0048] Figure 5 For compounds 2-3 1 1H NMR (400MHz acetone-d6)

[0049] Figure 6 For compounds 2-3 13 C10 NMR (100MHz acetone-d6)

[0050] Figure 7 For compounds 2-4 1 1H NMR (400MHz acetone-d6)

[0051] Figure 8 For compounds 2-4 13 C10 NMR (100MHz acetone-d6)

[0052] Figure 9 For compounds 2-5 1 1H NMR (400MHz acetone-d6)

[0053] Figure 10For compounds 2-5 13 C10 NMR (100MHz acetone-d6)

[0054] Figure 11 For compounds 2-6 1 1H NMR (400MHz acetone-d6)

[0055] Figure 12 For compounds 2-6 13 C10 NMR (100MHz acetone-d6)

[0056] Figure 13 For compounds 2-7 1 1H NMR (400MHz acetone-d6)

[0057] Figure 14 For compounds 2-7 13 C10 NMR (100MHz acetone-d6)

[0058] Figure 15 For compounds 2-8 1 H NMR (400MHz CDCl3)

[0059] Figure 16 For compounds 2-8 13 C NMR (100MHz CDCl3)

[0060] Figure 17 For compounds 2-9 1 H NMR (400MHz CDCl3)

[0061] Figure 18 For compounds 2-9 13 C NMR (100MHz CDCl3)

[0062] Figure 19 For compound 2-10 1 H NMR (400MHz CDCl3)

[0063] Figure 20 For compound 2-10 13 C NMR (100MHz CDCl3)

[0064] Figure 21 For compound 2-11 1 H NMR (400MHz CDCl3)

[0065] Figure 22 For compound 2-11 13 C NMR (100MHz CDCl3)

[0066] Figure 23 For compound 2-12 1 1H NMR (400MHz acetone-d6)

[0067] Figure 24 For compound 2-12 13 C10 NMR (100MHz acetone-d6)

[0068] Figure 25 For compound 2-13 1 H NMR (400MHz CDCl3)

[0069] Figure 26 For compound 2-13 13 C NMR (100MHz CDCl3)

[0070] Figure 27 For compound 2-14 1 H NMR (400MHz CDCl3)

[0071] Figure 28 For compound 2-14 13 C NMR (100MHz CDCl3)

[0072] Figure 29 For compound 2-15 1 H NMR (400MHz CDCl3)

[0073] Figure 30 For compound 2-15 13 C NMR (100MHz CDCl3)

[0074] Figure 31 For compound 2-16 1 H NMR (400MHz CDCl3)

[0075] Figure 32 For compound 2-16 13 C NMR (100MHz CDCl3)

[0076] Figure 33 For compound 2-17 1 H NMR (400MHz CDCl3)

[0077] Figure 34 For compound 2-17 13 C NMR (100MHz CDCl3)

[0078] Figure 35 For compound 2-181 H NMR (400MHz CDCl3)

[0079] Figure 36 For compound 2-18 13 C NMR (100MHz CDCl3)

[0080] Figure 37 For compound 2-19 1 H NMR (400MHz CDCl3)

[0081] Figure 38 For compound 2-19 13 C NMR (100MHz CDCl3)

[0082] Figure 39 For compound 2-20 1 H NMR (400MHz CDCl3)

[0083] Figure 40 For compound 2-20 13 C NMR (100MHz CDCl3)

[0084] Figure 41 For compound 2-21 1 H NMR (400MHz CDCl3)

[0085] Figure 42 For compound 2-21 13 C NMR (100MHz CDCl3)

[0086] Figure 43 For compound 2-22 1 H NMR (400MHz CDCl3)

[0087] Figure 44 For compound 2-22 13 C NMR (100MHz CDCl3)

[0088] Figure 45 For compound 2-23 1 1H NMR (400MHz acetone-d6)

[0089] Figure 46 For compound 2-23 13 C10 NMR (100MHz acetone-d6)

[0090] Figure 47 For compound 2-24 1 H NMR (400MHz CDCl3)

[0091] Figure 48 For compound 2-24 13 C NMR (100MHz CDCl3)

[0092] Figure 49 For compound 2-25 1 H NMR (400MHz CDCl3)

[0093] Figure 50 For compound 2-25 13 C NMR (100MHz CDCl3)

[0094] Figure 51 For compound 2-26 1 H NMR (400MHz CDCl3)

[0095] Figure 52 For compound 2-26 13 C NMR (100MHz CDCl3)

[0096] Figure 53 For compound 2-27 1 1H NMR (400MHz acetone-d6)

[0097] Figure 54 For compound 2-27 13 C10 NMR (100MHz acetone-d6) Detailed Implementation

[0098] The following embodiments are intended to enable those skilled in the art to more fully understand the present invention, but are not intended to limit the invention to the scope of the embodiments described.

[0099] (I) Implementation Examples

[0100] Example 1

[0101]

[0102] Synthesis of benzofuran-3(2H)-one (2-1): Under nitrogen protection, 2-bromo-1-(2-hydroxyphenyl)ethane-1-one (1-1) (70.0 mg, 0.33 mmol) was dissolved in CH3CN (1.7 mL), and then N,N-diisopropylethylamine (115 μL, 0.66 mmol, 2.0 eq.) was added at 0 °C. The reaction was maintained in an ice bath for 5 minutes, and then the reaction solution was placed at room temperature. TLC analysis was performed. The reaction solution was diluted with ethyl acetate, and the organic phase was washed successively with water and saturated brine. The organic phases were combined and dried with anhydrous sodium sulfate. The drying agent was removed by filtration, and the solvent was removed by vacuum distillation. The residue was purified by silica gel column chromatography (PE:EA = 100:1) to obtain a pale yellow solid (32.9 mg, 74%).

[0103] Structural data representation:

[0104] 1 H NMR (400MHz, CDCl3) δ7.68 (ddd, J=7.7, 1.6, 0.7Hz, 1H), 7.62 (ddd, J=8.6, 7.2, 1.5H z,1H),7.15(dt,J=8.4,0.8Hz,1H),7.10(ddd,J=7.8,7.2,0.8Hz,1H),4.63(s,2H); 13 C NMR (100MHz, CDCl3) δ200.10,174.14,138.05,124.22,122.15,121.28,113.81,74.84.

[0105] Example 2

[0106]

[0107] Synthesis of 6-methoxybenzofuran-3(2H)-one (2-2): Under nitrogen protection, 2-bromo-1-(2-hydroxy-4-methoxyphenyl)ethane-1-one (1-2) (366 mg, 1.5 mmol) was dissolved in acetonitrile (15 mL), and then N,N-diisopropylethylamine (523 μL, 3.0 mmol) was added at 0 °C. The reaction was maintained in an ice bath for 5 minutes, and then the reaction solution was placed at room temperature. TLC monitoring (petroleum ether: ethyl acetate = 3:1) showed that the reaction was complete. The reaction solution was diluted with ethyl acetate, and the organic phase was washed successively with water and saturated brine. The organic phases were combined and dried with anhydrous sodium sulfate. The drying agent was removed by filtration, and the solvent was removed by vacuum distillation. The residue was subjected to silica gel column chromatography (gradient eluent V(ethyl acetate):V(petroleum ether) = 1:100 to 1:20, dry loading) to give a pale yellow liquid (231 mg, yield 94%).

[0108] Structural data representation:

[0109] 1 H NMR (400MHz, CDCl3) δ: 7.53 (d, J = 8.6 Hz, 1H), 6.63 (dd, J = 8.6, 2.1 Hz, 1H), 6.53 (d, J = 2.1 Hz, 1H), 4.62 (d, J = 8.8 Hz, 2H), 3.87 (s, 3H); 13 C NMR (100MHz, CDCl3) δ: 197.51, 176.45, 168.13, 124.94, 114.25, 111.66, 96.24, 75.50, 55.88; IR (KBr): 2938.75, 1601.71, 1445.98, 1245.31; ESI-HRMS calcd for C9H8O3[MH] - 163.0474, found 163.0475.

[0110] Example 3

[0111]

[0112] Synthesis of 5-methoxybenzofuran-3(2H)-one (2-3): Under nitrogen protection, 2-bromo-1-(2-hydroxy-5-methoxyphenyl)ethane-1-one (1-3) (61 mg, 0.25 mmol, 1.0 eq.) was dissolved in CH3CN (1.3 mL), and then N,N-diisopropylethylamine (87 μL, 0.50 mmol, 2.0 eq.) was added at 0 °C. The reaction was maintained in an ice bath for 5 minutes, and then the reaction solution was placed at room temperature. After the reaction was complete as monitored by TLC, the reaction solution was diluted with ethyl acetate. The organic phase was washed successively with water and saturated brine. The organic phases were combined and dried with anhydrous sodium sulfate. The drying agent was removed by filtration, and the solvent was removed by vacuum distillation. The residue was purified by silica gel column chromatography (PE:EA = 50:1) to obtain a pale yellow solid (36.9 mg, 90%).

[0113] Structural data representation:

[0114] 1 H NMR (400MHz, Acetone-d6) δ7.31(dd,J=9.0,2.8Hz,1H),7.15(d,J=9.0Hz,1H),7.04(d,J=2.8Hz,1H),4.69(s,2H),3.83(s,3H); 13C NMR (100MHz, Acetone-d6) δ200.06,169.74,155.91,127.91,122.10,115.26,104.54,76.06,56.22.

[0115] Example 4

[0116]

[0117] Synthesis of 4-methoxybenzofuran-3(2H)-one (2-4): Under nitrogen protection, 2-bromo-1-(2-hydroxy-6-methoxyphenyl)ethane-1-one (1-4) (58 mg, 0.24 mmol, 1.0 eq.) was dissolved in CH3CN (1.2 mL), and then N,N-diisopropylethylamine DIPEA (84 μL, 0.48 mmol, 2.0 eq.) was added at 0 °C. The reaction was maintained in an ice bath for 5 min, and then the reaction solution was placed at room temperature. After the reaction was complete as monitored by TLC, the reaction solution was diluted with ethyl acetate. The organic phase was washed successively with water and saturated brine. The organic phases were combined and dried with anhydrous sodium sulfate. The drying agent was removed by filtration, and the solvent was removed by vacuum distillation. The residue was purified by silica gel column chromatography (PE:EA = 50:1) and then by column chromatography (PE:EA = 4:1) to obtain a white solid (38.6 mg, 98%).

[0118] Structural data representation:

[0119] 1 H NMR (400MHz, Acetone-d6) δ7.59(t,J=8.3Hz,1H),6.70(d,J=8.2Hz,1H),6.62(d,J=8.3Hz,1H),4.59(s,2H),3.90(s,3H); 13 C NMR (100MHz, Acetone-d6) δ196.61,175.79,158.96,140.02,111.16,105.84,104.28,75.22,56.22.

[0120] Example 5

[0121]

[0122] Synthesis of 6-hydroxybenzofuran-3(2H)-one (2-5): Under nitrogen protection, 2-bromo-1-(2,4-dihydroxyphenyl)ethane-1-one (1-5) (70 mg, 0.30 mmol, 1.0 eq.) was dissolved in CH3CN (1.5 mL). Then, N,N-diisopropylethylamine (105 μL, 0.60 mmol, 2.0 eq.) dissolved in CH3CN (1.5 mL) was added at 0 °C. The reaction was maintained in an ice bath for 5 minutes, and then the reaction solution was placed at room temperature. After the reaction was complete as detected by TLC, the reaction solution was diluted with ethyl acetate. The organic phase was washed successively with water and saturated brine. The organic phases were combined and dried with anhydrous sodium sulfate. The drying agent was removed by filtration, and the solvent was removed by vacuum distillation. The residue was purified by silica gel column chromatography (PE:EA = 50:1) and then by column chromatography (PE:EA = 5:1) to obtain a yellow solid (43.7 mg, 97%).

[0123] Structural data representation:

[0124] 1 H NMR (400MHz, Acetone-d6) δ9.74(s,1H),7.47(d,J=8.4Hz,1H),6.65(dd,J=8.5,2.0Hz,1H),6.54(d,J=2.0Hz,1H),4.62(s,2H); 13 C NMR (100MHz, Acetone-d6) δ197.26,176.90,167.17,125.83,114.63,112.32,99.34,75.95.

[0125] Example 6

[0126]

[0127] Synthesis of 5-hydroxybenzofuran-3(2H)-one (2-6): Under nitrogen protection, 2-bromo-1-(2,5-dihydroxyphenyl)ethane-1-one (1-6) (70 mg, 0.30 mmol, 1.0 eq.) was dissolved in CH3CN (1.5 mL), and then N,N-diisopropylethylamine (105 μL, 0.60 mmol, 2.0 eq.) was added at 0 °C. The reaction was maintained in an ice bath for 5 minutes, and then the reaction solution was placed at room temperature. After the reaction was complete as detected by TLC, the reaction solution was diluted with ethyl acetate. The organic phase was washed successively with water and saturated brine. The organic phases were combined and dried with anhydrous sodium sulfate. The drying agent was removed by filtration, and the solvent was removed by vacuum distillation. The residue was purified by silica gel column chromatography (PE:EA = 50:1) and then by column chromatography (PE:EA = 6:1) to obtain a yellow solid (34.7 mg, 77%).

[0128] Structural data representation:

[0129] 1 H NMR (400MHz, Acetone-d6) δ8.57(s,1H),7.24(dd,J=8.9,2.7Hz,1H),7.08(d,J=8.9Hz,1H),6.96(d,J=2.8Hz,1H),4.65(s,2H); 13 C NMR (100MHz, Acetone-d6) δ200.27,168.82,153.24,127.33,122.33,114.97,107.49,75.84.

[0130] Example 7

[0131]

[0132] Synthesis of 4-hydroxybenzofuran-3(2H)-one (2-7): Under nitrogen protection, 2-bromo-1-(2,6-dihydroxyphenyl)ethane-1-one (1-7) (76 mg, 0.33 mmol, 1.0 eq.) was dissolved in CH3CN (1.7 mL). Then, N,N-diisopropylethylamine (115 μL, 0.66 mmol, 2.0 eq.) was added at 0 °C, and the reaction was maintained in an ice bath for 5 minutes. The reaction mixture was then allowed to react at room temperature. TLC analysis showed that the reaction was complete. The reaction mixture was diluted with ethyl acetate, and the organic phase was washed successively with water and saturated brine. The organic phases were combined and dried over anhydrous sodium sulfate. The drying agent was removed by filtration, and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (PE:EA = 50:1) followed by column chromatography (PE:EA = 15:1) to obtain a white solid (48.1 mg, 97%).

[0133] Structural data representation:

[0134] 1 H NMR (400MHz, Acetone-d6) δ9.00(s,1H),7.50(t,J=8.2Hz,1H),6.61(dd,J=8.2,0.6Hz,1H),6.48(dd,J=8.2,0.6Hz,1H),4.65(s,2H); 13 C NMR (100MHz, Acetone-d6) δ199.15,174.66,156.98,140.24,110.32,108.80,104.44,75.16.

[0135] Example 8

[0136]

[0137] Synthesis of 3-oxo-2,3-dihydrobenzofuran-6-acetic acid ester (2-8): Under nitrogen protection, 4-(2-bromoacetyl)-3-hydroxyphenylacetic acid ester (1-8) (80 mg, 0.29 mmol, 1.0 eq.) was dissolved in CH3CN (1.5 mL). Then, N,N-diisopropylethylamine (101 μL, 0.58 mmol, 2.0 eq.) was added at 0 °C. The reaction was maintained in an ice bath for 5 minutes, and then the reaction mixture was allowed to react at room temperature. TLC analysis showed that the reaction was complete. The reaction mixture was diluted with ethyl acetate, and the organic phase was washed successively with water and saturated brine. The organic phases were combined and dried over anhydrous sodium sulfate. The drying agent was removed by filtration, and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (PE:EA = 50:1) followed by column chromatography (PE:EA = 10:1) to obtain a yellow solid (50.3 mg, 90%).

[0138] Structural data representation:

[0139] 1 H NMR (400MHz, CDCl3) δ7.66(d,J=8.4Hz,1H),6.92(d,J=1.9Hz,1H),6.82(dd,J=8.4,1.9Hz,1H),4.65(s,2H),2.32(s,3H); 13 C NMR (100MHz, CDCl3) δ198.41,174.87,168.58,158.37,125.08,118.96,116.57,107.22,75.58,21.30.

[0140] Example 9

[0141]

[0142] Synthesis of 3-oxo-2,3-dihydrobenzofuran-5-acetic acid ester (2-9): Under nitrogen protection, 3-(2-bromoacetyl)-4-hydroxyphenylacetic acid ester (1-9) (114 mg, 0.42 mmol, 1.0 eq.) was dissolved in CH3CN (2.1 mL), and then N,N-diisopropylethylamine (147 μL, 0.84 mmol, 2.0 eq.) was added at 0 °C. The reaction was maintained in an ice bath for 5 minutes, and then the reaction solution was placed at room temperature. After the reaction was confirmed to be complete by TLC, the reaction solution was diluted with ethyl acetate. The organic phase was washed successively with water and saturated brine. The organic phases were combined and dried with anhydrous sodium sulfate. The drying agent was removed by filtration, and the solvent was removed by vacuum distillation. The residue was purified by silica gel column chromatography (PE:EA = 50:1) and then by column chromatography (PE:EA = 15:1) to obtain a yellow solid (66.3 mg, 82%).

[0143] Structural data representation:

[0144] 1 H NMR (400MHz, CDCl3) δ7.37(d,J=2.4Hz,1H),7.32(dd,J=8.9,2.6Hz,1H),7.16–7.11(m,1H),4.67(s,2H),2.30(s,3H); 13 C NMR (100MHz, CDCl3) δ199.24,171.56,169.67,145.25,131.86,121.64,116.46,114.46,75.70,21.11.

[0145] Example 10

[0146]

[0147] Synthesis of 3-oxo-2,3-dihydrobenzofuran-4-acetate (2-10): Under nitrogen protection, 2-(2-bromoacetyl)-3-hydroxyphenylacetate (1-10) (60 mg, 0.22 mmol, 1.0 eq.) was dissolved in CH3CN (1.1 mL), and then N,N-diisopropylethylamine (77 μL, 0.44 mmol, 2.0 eq.) was added at 0 °C. The reaction was maintained in an ice bath for 5 minutes, and then the reaction solution was placed at room temperature. After the reaction was confirmed to be complete by TLC, the reaction solution was diluted with ethyl acetate. The organic phase was washed successively with water and saturated brine. The organic phases were combined and dried with anhydrous sodium sulfate. The drying agent was removed by filtration, and the solvent was removed by vacuum distillation. The residue was purified by silica gel column chromatography (PE:EA = 50:1) and then by column chromatography (PE:EA = 10:1) to obtain a yellow solid (39.8 mg, 94%).

[0148] Structural data representation:

[0149] 1 H NMR (400MHz, CDCl3) δ7.59(dd,J=8.5,7.9Hz,1H),7.00(dd,J=8.4,0.7Hz,1H),6.72(dd,J=7.9,0.7Hz,1H),4.61(s,2H),2.38(s,3H); 13 C NMR (100MHz, CDCl3) δ196.58,174.42,168.73,147.25,138.81,114.83,114.26,111.38,74.97,20.79.

[0150] Example 11

[0151]

[0152] Synthesis of 5-nitrobenzofuran-3(2H)-one (2-11): Under nitrogen protection, 2-bromo-1-(2-hydroxy-5-nitrophenyl)ethane-1-one (1-11) (133 mg, 0.51 mmol, 1.0 eq.) was reacted in an ice bath for 5 min. Then, N,N-diisopropylethylamine (178 μL, 1.02 mmol, 2.0 eq.) was added at 0 °C, and the reaction was maintained in an ice bath for 5 min. The reaction solution was then placed at room temperature. After TLC detection showed that the reaction was complete, the reaction solution was diluted with ethyl acetate. The organic phase was washed successively with water and saturated brine. The organic phases were combined and dried with anhydrous sodium sulfate. The drying agent was removed by filtration, and the solvent was removed by vacuum distillation. The residue was purified by silica gel column chromatography. The purification was carried out by column chromatography (PE:EA = 50:1) and then by column chromatography (PE:EA = 10:1) to obtain a pale yellow solid (46.9 mg, 51%).

[0153] Structural data representation:

[0154] 1 H NMR (400MHz, CDCl3) δ8.57(d,J=2.5Hz,1H),8.52(dd,J=9.1,2.5Hz,1H),7.28(d,J=9.1Hz,1H),4.83(s,2H); 13 C NMR (100MHz, CDCl3) δ197.45,176.64,143.02,132.92,121.59,121.08,114.60,76.58.

[0155] Example 12

[0156]

[0157] Synthesis of 3-oxo-2,3-dihydrobenzofuran-5-onitrile (2-12): Under nitrogen protection, 3-(2-bromoacetyl)-4-hydroxybenzyl nitrile (1-12) (121.0 mg, 0.50 mmol, 1.0 eq.) was dissolved in CH3CN (2.5 mL). Then, N,N-diisopropylethylamine (175 μL, 1.00 mmol, 2.0 eq.) was added at 0 °C. The reaction was maintained in an ice bath for 5 minutes, and then the reaction mixture was allowed to react at room temperature. After TLC detection showed complete reaction, the reaction mixture was diluted with ethyl acetate. The organic phase was washed successively with water and saturated brine. The organic phases were combined and dried over anhydrous sodium sulfate. The drying agent was removed by filtration, and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (PE:EA = 50:1) followed by column chromatography (PE:EA = 10:1) to obtain a yellow solid (45.7 mg, 57%).

[0158] Structural data representation:

[0159] 1 H NMR (400MHz, Acetone-d6) δ8.09(d,J=1.7Hz,1H),8.08–8.04(m,1H),7.44(d,J=8.6Hz,1H),4.89(s,2H); 13 C NMR (100MHz, Acetone-d6) δ198.22,176.18,141.49,129.69,123.14,118.59,116.00,106.39,76.51.

[0160] Example 13

[0161]

[0162] Synthesis of 5-fluorobenzofuran-3(2H)-one (2-13): Under nitrogen protection, 2-bromo-1-(5-fluoro-2-hydroxyphenyl)ethane-1-one (1-13) (80.0 mg, 0.34 mmol, 1.0 eq.) was dissolved in CH3CN (1.7 mL), and then N,N-diisopropylethylamine (118 μL, 0.68 mmol, 2.0 eq.) was added at 0 °C. The reaction was maintained in an ice bath for 5 minutes, and then the reaction solution was placed at room temperature. After the reaction was confirmed to be complete by TLC, the reaction solution was diluted with ethyl acetate. The organic phase was washed successively with water and saturated brine. The organic phases were combined and dried with anhydrous sodium sulfate. The drying agent was removed by filtration, and the solvent was removed by vacuum distillation. The residue was purified by silica gel column chromatography (PE:EA = 50:1) and then by column chromatography (PE:EA = 100:1) to obtain a yellow solid (25.4 mg, 49%).

[0163] Structural data representation:

[0164] 1 H NMR (400MHz, CDCl3) δ7.35(td,J=8.7,2.9Hz,1H),7.31(dd,J=6.7,2.8Hz,1H),7.11(dd,J=8.9,3.6Hz,1H),4.68(s,2H); 13 C NMR (100MHz, CDCl3) δ199.47 (d, J = 3.2Hz), 170.25, 157.88 (d, J = 243.3Hz), 125.79 (d , J=26.0Hz), 121.72 (d, J=8.0Hz), 114.91 (d, J=7.8Hz), 109.25 (d, J=23.8Hz), 75.82.

[0165] Example 14

[0166]

[0167] Synthesis of 5-chlorobenzofuran-3(2H)-one (2-14): Under nitrogen protection, 2-bromo-1-(5-fluoro-2-hydroxyphenyl)ethane-1-one (1-14) (70.0 mg, 0.28 mmol, 1.0 eq.) was dissolved in CH3CN (1.4 mL). Then, N,N-diisopropylethylamine (101 μL, 0.56 mmol, 2.0 eq.) was added at 0 °C. The reaction was maintained in an ice bath for 5 minutes, and then the reaction mixture was allowed to react at room temperature. TLC analysis showed that the reaction was complete. The reaction mixture was diluted with ethyl acetate, and the organic phase was washed successively with water and saturated brine. The organic phases were combined and dried over anhydrous sodium sulfate. The drying agent was removed by filtration, and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (PE:EA = 50:1) and then by column chromatography (PE:EA = 100:1) to obtain a yellow solid (31.2 mg, 66%).

[0168] Structural data representation:

[0169] 1 H NMR (400MHz, CDCl3) δ7.62 (dd, J=2.3, 0.6Hz, 1H), 7.55 (dd, J=8.8, 2.4Hz, 1H), 7.10 (dd, J=8.8, 0.6Hz, 1H), 4.67 (s, 2H); 13 C NMR (100MHz, CDCl3) δ198.63,172.36,137.89,127.73,123.61,122.38,115.12,75.56.

[0170] Example 15

[0171]

[0172] Synthesis of 5-bromobenzofuran-3(2H)-one (2-15): Under nitrogen protection, 2-bromo-1-(5-bromo-2-hydroxyphenyl)ethane-1-one (1-15) (80.0 mg, 0.27 mmol, 1.0 eq.) was dissolved in CH3CN (1.4 mL), and then N,N-diisopropylethylamine (94 μL, 0.54 mmol, 2.0 eq.) was added at 0 °C. The reaction was maintained in an ice bath for 5 minutes, and then the reaction solution was placed at room temperature. After the reaction was confirmed to be complete by TLC, the reaction solution was diluted with ethyl acetate. The organic phase was washed successively with water and saturated brine. The organic phases were combined and dried with anhydrous sodium sulfate. The drying agent was removed by filtration, and the solvent was removed by vacuum distillation. The residue was purified by silica gel column chromatography (PE:EA = 50:1) and then by column chromatography (PE:EA = 100:1) to obtain a yellow solid (34.0 mg, 59%).

[0173] Structural data representation:

[0174] 1 H NMR (400MHz, CDCl3) δ7.79 (d, J = 2.2Hz, 1H), 7.69 (dd, J = 8.8, 2.2Hz, 1H), 7.06 (d, J = 8.8Hz, 1H), 4.67 (s, 2H); 13 C NMR (100MHz, CDCl3) δ198.42,172.79,140.59,126.81,122.98,115.59,114.79,75.41.

[0175] Example 16

[0176]

[0177] Synthesis of 6-fluorobenzofuran-3(2H)-one (2-16): Under nitrogen protection, 2-bromo-1-(4-fluoro-2-hydroxyphenyl)ethane-1-one (1-16) (80.0 mg, 0.34 mmol, 1.0 eq.) was dissolved in CH3CN (1.7 mL). Then, N,N-diisopropylethylamine (118 μL, 0.68 mmol, 2.0 eq.) was added at 0 °C. The reaction was maintained in an ice bath for 5 minutes, and then the reaction mixture was allowed to react at room temperature. TLC analysis showed that the reaction was complete. The reaction mixture was diluted with ethyl acetate, and the organic phase was washed successively with water and saturated brine. The organic phases were combined and dried over anhydrous sodium sulfate. The drying agent was removed by filtration, and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (PE:EA = 50:1) and then by column chromatography (PE:EA = 100:1) to obtain a yellow solid (29.1 mg, 56%).

[0178] Structural data representation:

[0179] 1 H NMR (400MHz, CDCl3) δ7.66 (dd, J=9.1, 5.8Hz, 1H), 6.81 (ddd, J=9.0, 4.5, 2.4Hz, 2H), 4.66 (s, 2H); 13 C NMR (100MHz, CDCl3) δ197.87, 175.48 (d, J = 14.9Hz), 169.31 (d, J = 258.1Hz), 126.08 (d , J=12.2Hz), 117.93 (d, J=1.7Hz), 111.05 (d, J=24.5Hz), 101.13 (d, J=26.0Hz), 75.78.

[0180] Example 17

[0181]

[0182] Synthesis of 6-(benzyloxy)benzofuran-3(2H)-one (2-17): Under nitrogen protection, 1-(4-(benzyloxy)-2-hydroxyphenyl)-2-bromoethane-1-one (1-17) (40.0 mg, 0.12 mmol, 1.0 eq.) was dissolved in CH3CN (0.6 mL), and then N,N-diisopropylethylamine (42 μL, 0.24 mmol, 2.0 eq.) was added at 0 °C. The reaction was maintained in an ice bath for 5 minutes, and then the reaction solution was placed at room temperature. After the reaction was complete as detected by TLC, the reaction solution was diluted with ethyl acetate. The organic phase was washed successively with water and saturated brine. The organic phases were combined and dried with anhydrous sodium sulfate. The drying agent was removed by filtration, the solvent was removed by vacuum distillation, and the residue was subjected to silica gel column chromatography. Purified by column chromatography (PE:EA = 50:1) and column chromatography (PE:EA = 35:1), a yellow solid (27.1 mg, 94%) was obtained.

[0183] Structural data representation:

[0184] 1 H NMR (400MHz, CDCl3) δ7.58(d,J=8.6Hz,1H),7.51–7.32(m,5H),6.73(dd,J=8.7,2.1Hz,1H),6.62(d,J=2.1Hz,1H),5.13(s,2H),4.62(s,2H); 13 C NMR (100MHz, CDCl3) δ197.76,176.54,167.33,135.61,128.91,128.60,127.67,125.30,114.64,112.35,97.49,75.68,70.72.

[0185] Example 18

[0186]

[0187] Synthesis of 5-((tert-butyldimethylsilyl)oxy)benzofuran-3(2H)-one (2-18): Under nitrogen protection, 2-bromo-1-(5-((tert-butyldimethylsilyl)oxy)-2-hydroxyphenyl)ethane-1-one (1-18) (68.0 mg, 0.20 mmol, 1.0 eq.) was dissolved in CH3CN (1.0 mL). Then, N,N-diisopropylethylamine (70 μL, 0.40 mmol, 2.0 eq.) was added at 0 °C, and the reaction was maintained in an ice bath for 5 minutes. The reaction mixture was then allowed to react at room temperature. TLC analysis showed that the reaction was complete. The reaction mixture was diluted with ethyl acetate, and the organic phase was washed successively with water and saturated brine. The organic phases were combined and dried over anhydrous sodium sulfate. The drying agent was removed by filtration, and the solvent was removed under reduced pressure. The residue was subjected to silica gel column chromatography. Purified by column chromatography (PE:EA = 50:1), then purified by column chromatography (PE:EA = 100:1), yielding a yellow liquid (42.1 mg, 80%).

[0188] Structural data representation:

[0189] 1 H NMR (400MHz, CDCl3) δ7.14(dd,J=8.9,2.7Hz,1H),7.04(d,J=2.6Hz,1H),7.01(d,J=8.9Hz,1H),4.62(s,2H),0.97(s,9H),0.18(s,6H); 13 C NMR (100MHz, CDCl3) δ200.37,169.37,150.72,131.53,121.54,114.26,112.64,75.55,25.74,18.29,-4.43.

[0190] Example 19

[0191]

[0192] Synthesis of 5-bromonaphtho[1,2-b]furan-3(2H)-one (2-19): Under nitrogen protection, 2-bromo-1-(4-bromo-1-hydroxynaphthyl-2-yl)ethane-1-one (1-19) (79.0 mg, 0.23 mmol, 1.0 eq.) was dissolved in CH3CN (1.2 mL). Then, N,N-diisopropylethylamine (80 μL, 0.46 mmol, 2.0 eq.) was added at 0 °C, and the reaction was carried out in an ice bath for 5 minutes. The reaction solution was then placed at room temperature. After the reaction was confirmed to be complete by TLC, the reaction solution was diluted with ethyl acetate. The organic phase was washed successively with water and saturated brine. The organic phases were combined and dried with anhydrous sodium sulfate. The drying agent was removed by filtration, the solvent was removed by vacuum distillation, and the residue was subjected to silica gel column chromatography. Purified by column chromatography (PE:EA = 50:1) and column chromatography (PE:EA = 100:1), a yellow solid (60.0 mg, 99%) was obtained.

[0193] Structural data representation:

[0194] 1 H NMR(400MHz, CDCl3)δ8.28(dt,J=8.5,0.9Hz,1H),8.28–8.21(m,1H),7.86(s,1H), 7.83(ddd,J=8.5,7.0,1.3Hz,1H),7.68(ddd,J=8.1,7.0,1.1Hz,1H),4.85(s,2H); 13 CNMR (100MHz, CDCl3) δ197.52,173.95,136.18,132.04,128.45,127.82,122.82,122.69,122.28,116.64,116.23,76.07.

[0195] Example 20

[0196]

[0197] Synthesis of naphtho[1,2-b]furan-3(2H)-one (2-20): Under nitrogen protection, 2-bromo-1-(1-hydroxynaphthyl-2-yl)ethane-1-one (1-20) (58.0 mg, 0.22 mmol, 1.0 eq.) was dissolved in CH3CN (1.1 mL), and then N,N-diisopropylethylamine (77 μL, 0.44 mmol, 2.0 eq.) was added at 0 °C. The reaction was maintained in an ice bath for 5 minutes, and then the reaction solution was placed at room temperature. After the reaction was complete as detected by TLC, the reaction solution was diluted with ethyl acetate. The organic phase was washed successively with water and saturated brine. The organic phases were combined and dried with anhydrous sodium sulfate. The drying agent was removed by filtration, and the solvent was removed by vacuum distillation. The residue was purified by silica gel column chromatography (PE:EA = 50:1) and then purified by column chromatography (PE:EA = 100:1) to obtain a yellow solid (39.3 mg, 97%).

[0198] Structural data representation:

[0199] 1 H NMR (400MHz, CDCl3) δ8.23 (d, J=8.2, 0.9Hz, 1H), 7.89 (dd, J=8.2, 1.1Hz, 1H), 7.71 (ddd, J=8.3, 7.0, 1. 4Hz,1H),7.61(ddd,J=8.2,7.0,1.3Hz,1H),7.57(d,J=8.6Hz,1H),7.46(d,J=8.5Hz,1H),4.84(s,2H); 13 C NMR (100MHz, CDCl3) δ199.21,174.83,138.66,130.84,128.58,126.96,122.73,122.33,121.90,118.69,116.15,75.95.

[0200] Example 21

[0201]

[0202] Synthesis of 5,7-dibromobenzofuran-3(2H)-one (2-21): Under nitrogen protection, 2-bromo-1-(3,5-dibromo-2-hydroxyphenyl)ethane-1-one (1-21) (70.0 mg, 0.19 mmol, 1.0 eq.) was dissolved in CH3CN (2.0 mL). Then, N,N-diisopropylethylamine (86 μL, 0.38 mmol, 2.0 eq.) was added at 0 °C. The reaction was maintained in an ice bath for 5 minutes, and then the reaction mixture was allowed to react at room temperature. TLC analysis showed that the reaction was complete. The reaction mixture was diluted with ethyl acetate, and the organic phase was washed successively with water and saturated brine. The organic phases were combined and dried over anhydrous sodium sulfate. The drying agent was removed by filtration, and the solvent was removed by vacuum distillation. The residue was then subjected to silica gel column chromatography. Purified by column chromatography (PE:EA = 50:1), then purified by column chromatography (PE:EA = 100:1), yielding a pale yellow solid (25.7 mg, 46%).

[0203] Structural data representation:

[0204] 1 H NMR (400MHz, CDCl3) δ7.91 (d, J = 2.0Hz, 1H), 7.75 (d, J = 2.0Hz, 1H), 4.77 (s, 2H); 13 C NMR (100MHz, CDCl3) δ197.40,169.42,142.35,125.88,123.91,115.08,108.04,75.97.

[0205] Example 22

[0206]

[0207] Synthesis of 2-benzylbenzofuran-3(2H)-one (2-22): Under nitrogen protection, 2-bromo-1-(2-hydroxyphenyl)-3-phenylprop-1-one (1-22) (100.0 mg, 0.33 mmol, 1.0 eq.) was dissolved in CH3CN (1.7 mL). Then, N,N-diisopropylethylamine (115 μL, 0.66 mmol, 2.0 eq.) was added at 0 °C. The reaction was maintained in an ice bath for 5 minutes, and then the reaction mixture was allowed to react at room temperature. TLC analysis showed that the reaction was complete. The reaction mixture was diluted with ethyl acetate, and the organic phase was washed successively with water and saturated brine. The organic phases were combined and dried over anhydrous sodium sulfate. The drying agent was removed by filtration, and the solvent was removed by vacuum distillation. The residue was purified by silica gel column chromatography (PE:EA = 50:1), yielding a yellow liquid (66.5 mg, 90%).

[0208] Structural data representation:

[0209] 1 H NMR (400MHz, CDCl3) δ7.63 (dd, J=7.8, 1.3Hz, 1H), 7.58 (tt, J=7.2, 1.4Hz, 1H), 7.33–7.22 (m, 5H ),4.79(ddd,J=8.8,3.6,0.9Hz,1H),3.37(dd,J=14.7,3.5Hz,1H),2.99(dd,J=14.6,8.7Hz,1H); 13 C NMR (100MHz, CDCl3) δ201.28,172.78,138.23,136.19,129.51,128.60,127.08,124.43,122.03,121.04,113.69,85.94,37.56.

[0210] Example 23

[0211]

[0212] Synthesis of 4,6-dihydroxybenzofuran-3(2H)-one (2-23): Under nitrogen protection, 2-bromo-1-(2,4,6-trihydroxyphenyl)ethane-1-one (1-23) (101.0 mg, 0.41 mmol, 1.0 eq.) was dissolved in CH3CN (2.1 mL). Then, N,N-diisopropylethylamine (143 μL, 0.82 mmol, 2.0 eq.) was added at 0 °C, and the reaction was maintained in an ice bath for 5 minutes. The reaction mixture was then allowed to react at room temperature. TLC analysis showed that the reaction was complete. The reaction mixture was diluted with ethyl acetate, and the organic phase was washed successively with water and saturated brine. The organic phases were combined and dried over anhydrous sodium sulfate. The drying agent was removed by filtration, and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (PE:EA = 50:1) followed by column chromatography (PE:EA = 4:1), yielding a pale red solid (66.1 mg, 97%).

[0213] Structural data representation:

[0214] 1 H NMR (400MHz, Acetone-d6) δ6.05 (d, J = 1.7Hz, 1H), 5.99 (d, J = 1.7Hz, 1H), 4.59 (s, 2H); 13 C NMR (100MHz, Acetone-d6) δ196.60,176.19,168.98,158.20,103.97,96.97,91.71,75.83.

[0215] Example 24

[0216]

[0217] Synthesis of 7-bromo-6-methoxybenzofuran-3(2H)-one (2-24): Under nitrogen protection, 2-bromo-1-(3-bromo-2-hydroxy-4-methoxyphenyl)ethane-1-one (1-24) (80.0 mg, 0.25 mmol, 1.0 eq.) was dissolved in CH3CN (1.3 mL). Then, N,N-diisopropylethylamine (96 μL, 0.50 mmol, 2.0 eq.) was added at 0 °C. The reaction was maintained in an ice bath for 5 minutes, and then the reaction mixture was allowed to react at room temperature. TLC analysis showed that the reaction was complete. The reaction mixture was diluted with ethyl acetate, and the organic phase was washed successively with water and saturated brine. The organic phases were combined and dried over anhydrous sodium sulfate. The drying agent was removed by filtration, and the solvent was removed under reduced pressure. The residue was subjected to silica gel column chromatography. Purified by column chromatography (PE:EA = 50:1), a pale yellow solid (59.6 mg, 98%) was obtained.

[0218] Structural data representation:

[0219] 1 H NMR (400MHz, CDCl3) δ7.63 (d, J = 8.5Hz, 1H), 6.72 (d, J = 8.6Hz, 1H), 4.74 (s, 2H), 4.02 (s, 3H); 13 C NMR (100MHz, CDCl3) δ197.43,171.86,163.91,124.24,116.24,106.84,94.68,76.14,57.32.

[0220] Example 25

[0221]

[0222] Synthesis of 5-bromo-6-methoxybenzofuran-3(2H)-one (2-25): Under nitrogen protection, 2-bromo-1-(5-bromo-2-hydroxy-4-methoxyphenyl)ethane-1-one (1-25) (80.0 mg, 0.25 mmol, 1.0 eq.) was dissolved in CH3CN (1.3 mL). Then, N,N-diisopropylethylamine (96 μL, 0.50 mmol, 2.0 eq.) was added at 0 °C. The reaction was maintained in an ice bath for 5 minutes, and then the reaction mixture was allowed to react at room temperature. TLC analysis showed that the reaction was complete. The reaction mixture was diluted with ethyl acetate, and the organic phase was washed successively with water and saturated brine. The organic phases were combined and dried over anhydrous sodium sulfate. The drying agent was removed by filtration, and the solvent was removed by vacuum distillation. The residue was then subjected to silica gel column chromatography. Purified by column chromatography (PE:EA = 50:1), a pale yellow solid (56.5 mg, 93%) was obtained.

[0223] Structural data representation:

[0224] 1 H NMR (400MHz, CDCl3) δ7.84(s,1H),6.60(s,1H),4.65(s,2H),3.98(s,3H); 13 CNMR (100MHz, CDCl3) δ196.51,175.41,163.55,128.11,115.15,106.79,96.24,75.88,57.05.

[0225] Example 26

[0226]

[0227] Synthesis of 7-bromo-3-oxo-2,3-dihydrobenzofuran-5-acetic acid ester (2-26): Under nitrogen protection, 3-bromo-5-(2-bromoacetyl)-4-hydroxyphenylacetic acid ester (1-26) (99.0 mg, 0.28 mmol, 1.0 eq.) was dissolved in CH3CN (1.4 mL). Then, N,N-diisopropylethylamine (98 μL, 0.56 mmol, 2.0 eq.) was added at 0 °C. The reaction was maintained in an ice bath for 5 minutes, and then the reaction mixture was allowed to react at room temperature. TLC analysis showed that the reaction was complete. The reaction mixture was diluted with ethyl acetate, and the organic phase was washed successively with water and saturated brine. The organic phases were combined and dried over anhydrous sodium sulfate. The drying agent was removed by filtration, the solvent was removed by vacuum distillation, and the residue was subjected to silica gel column chromatography. Purified by column chromatography (PE:EA = 50:1) and column chromatography (PE:EA = 20:1), a pale yellow solid (63.0 mg, 83%) was obtained.

[0228] Structural data representation:

[0229] 1 H NMR (400MHz, CDCl3) δ7.57 (d, J = 2.4Hz, 1H), 7.36 (d, J = 2.4Hz, 1H), 4.78 (s, 2H), 2.31 (s, 3H); 13 C NMR (100MHz, CDCl3) δ198.28,169.34,168.18,145.45,134.29,122.54,115.84,106.87,76.24,21.05.

[0230] Example 27

[0231]

[0232] Synthesis of 7-bromo-5-hydroxybenzofuran-3(2H)-one (2-27): Under nitrogen protection, 2-bromo-1-(3-bromo-2,5-dihydroxyphenyl)ethane-1-one (1-27) (90.0 mg, 0.29 mmol, 1.0 eq.) was dissolved in CH3CN (1.5 mL), and then N,N-diisopropylethylamine (101 μL, 0.58 mmol, 2.0 eq.) was added at 0 °C. The reaction was carried out in an ice bath for 5 minutes, and then the reaction solution was placed at room temperature. After the reaction was confirmed to be complete by TLC, the reaction solution was diluted with ethyl acetate. The organic phase was washed successively with water and saturated brine. The organic phases were combined and dried with anhydrous sodium sulfate. The drying agent was removed by filtration, the solvent was removed by vacuum distillation, and the residue was subjected to silica gel column chromatography. Purified by column chromatography (PE:EA = 50:1) and column chromatography (PE:EA = 10:1), a yellow solid (40.0 mg, 60%) was obtained.

[0233] Structural data representation:

[0234] 1 H NMR (400MHz, Acetone-d6) δ9.03 (s, 1H), 7.44 (d, J = 2.5Hz, 1H), 6.99 (d, J = 2.5Hz, 1H), 4.78 (s, 2H); 13 C NMR (100MHz, Acetone-d6) δ199.65,164,97,153.86,129.06,123.75,107.61,106.73,76.47.

[0235] (II) Experimental Results

[0236] The reaction processes of Examples 1-27 were tested, and the yields of each example were determined as follows:

[0237] Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art may make various modifications and alterations without departing from the spirit and scope of the present invention, and all such modifications and alterations shall be within the protection scope of the present invention.

Claims

1. A method for preparing benzofuran involving an organic base, characterized in that, Includes the following steps: The brominated compound (1) shown in Formula 1 is reacted with a catalyst to generate benzofuran-3(2H)-ketone compounds, as shown in Formula 1: in, R1 is selected from H, Any one or more of them; R6 is selected from any one or more of F, Cl, Br, and I; R2 is selected from any one or more of H; R3 is selected from any one or more of H, CH3O-, -OH, -OAc, F, and -OBn; R4 is selected from any one or more of H, CH3O-, -OH, -OAc, -NO2, -CN, F, Cl, Br, and -TBSOMe; R5 is selected from any one or more of H, CH3O-, -OH, and -OAc; Alternatively, R2 and R3 can form a ring, i.e., the structure of Equation 1 is...

2. The method for preparing benzofuran involving an organic base according to claim 1, characterized in that, The catalyst for the reaction is N,N-diisopropylethylamine.

3. The method for preparing benzofuran involving an organic base according to claim 1, characterized in that, The reaction solvent is acetonitrile.

4. The method for preparing benzofuran involving an organic base according to claim 1, characterized in that, The ratio of the compound of Formula 1 to the catalyst reaction equivalent is 1:1 to 3; further, the ratio of the compound of Formula 1 to the catalyst reaction equivalent is 1:

2.

5. The method for preparing benzofuran involving an organic base according to claim 1, characterized in that, The reaction was carried out at room temperature.

6. The method for preparing benzofuran involving an organic base according to claim 1, characterized in that, The compound of Formula 1 is selected from any one or more of the following compounds:

7. The method for preparing benzofuran involving an organic base according to claim 1, characterized in that, The compound of Formula 2 is selected from any one or more of the following compounds:

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