A method for the synthesis of 11,11-dimethyl-11H-benzo[B]fluorene

Abstract

The application relates to the technical field of light-emitting materials, in particular to a synthesis method of 11,11-dimethyl-11H-benzo[B]fluorene, which comprises the following two steps: S1, intermediate synthesis, under an inert atmosphere, 2-amino-3-bromonaphthalene is subjected to a coupling reaction with 2-phenylpropane-2-boronic acid pinacol ester in a palladium catalyst, an alkali and a mixed solvent to obtain an intermediate alpha,alpha-dimethyl-2-(2-naphthyl)-benzylamine; and S2, product synthesis, the intermediate is subjected to a ring-closing reaction in a solvent in the presence of concentrated nitric acid and potassium thiocyanate to obtain 11,11-dimethyl-11H-benzo[B]fluorene. The application shortens the reaction steps, is high in efficiency and safe and reliable in reaction.

Description

Technical Field

[0001] This invention belongs to the field of luminescent materials technology, and specifically relates to a method for synthesizing 11,11-dimethyl-11H-benzo[B]fluorene. Background Technology

[0002] 11,11-Dimethyl-11H-benzo[B]fluorene is an important intermediate for luminescent materials. It has a methylene group that anchors two benzene rings in a single plane, resulting in a more rigid structure, better thermal stability, longer wavelength conjugated absorption, and more pronounced electroluminescence. It is commonly used in the synthesis of various luminescent materials.

[0003] The synthesis methods for 11,11-dimethyl-11H-benzo[B]fluorene fall into two categories: one involves a cyclization reaction between phthalaldehyde and indanone to obtain 11H-benzo[B]fluorene ketone, followed by reduction and methylation with iodomethane to yield 11,11-dimethyl-11H-benzo[B]fluorene, as illustrated in patent WO2018070773, which discloses an organic electroluminescent device. The preparation scheme for 11,11-dimethyl-11H-benzo[B]fluorene is as follows: This method involves many steps, and iodomethane has a low boiling point, high toxicity, and is expensive, making it unsuitable for industrial production.

[0004] Another type involves obtaining 2-phenylnaphthalene-3-carboxylate via CC coupling, followed by Grignard reaction for methylation, and then Lewis acid-catalyzed cyclization to obtain 11,11-dimethyl-11H-benzo[B]fluorene. For example, patent CN110655438 discloses a compound with cycloheptene as its core and its application in organic electroluminescent devices. The preparation scheme for 11,11-dimethyl-11H-benzo[B]fluorene is as follows: The methyl Grignard reagent in this scheme is easily flammable and poses a high risk, and the numerous reaction steps result in high production costs.

[0005] Therefore, it is necessary to improve the existing synthetic techniques for 11,11-dimethyl-11H-benzo[B]fluorene in order to obtain a more economical and efficient new synthetic route. Summary of the Invention

[0006] The technical problem to be solved by the present invention is to provide a method for synthesizing 11,11-dimethyl-11H-benzo[B]fluorene, which shortens the reaction steps, is highly efficient, and is safe and reliable.

[0007] To achieve the above objectives, the present invention employs the following technical solution: A method for synthesizing 11,11-dimethyl-11H-benzo[B]fluorene comprises the following two reaction steps: S1, intermediate synthesis Under an inert atmosphere, 2-amino-3-bromonaphthalene and 2-phenylpropane-2-boronic acid pinacol ester were coupled together in a palladium catalyst, a base and a mixed solvent to give the intermediate α,α-dimethyl-2-(2-naphthyl)-phenylmethylamine. S2, Product Synthesis The intermediate underwent a cyclization reaction in a solvent in the presence of concentrated nitric acid and potassium thiocyanate to give 11,11-dimethyl-11H-benzo[B]fluorene.

[0008] Preferably, in step S1, the volume ratio of the mixed solvent to the mass ratio of 2-amino-3-bromonaphthalene is (10-20):1; the mixed solvent is a mixture of toluene, water and ethanol, with a volume ratio of toluene:water:ethanol = (3-3.5):(1-1.5):1.

[0009] Preferably, in step S1, the palladium catalyst is selected from tetra(triphenylphosphine)palladium or bis(dibenzylacetone)palladium; the base is an inorganic base, selected from potassium carbonate or potassium hydroxide; when the palladium catalyst is bis(dibenzylacetone)palladium, a phosphine ligand is also added to the reaction system in step S1, and the phosphine ligand is selected from triphenylphosphine or tricyclohexylphosphine; the molar ratio of the phosphine ligand to 2-amino-3-bromonaphthalene is (0.05-0.1):1.

[0010] Preferably, in step S1, the molar ratio of 2-phenylpropane-2-boronic acid pinacol ester to 2-amino-3-bromonaphthalene is (1-1.2):1; the molar ratio of the catalyst to 2-amino-3-bromonaphthalene is (0.025-0.05):1; and the molar ratio of the base to 2-amino-3-bromonaphthalene is (2-4):1.

[0011] Preferably, in step S1, the coupling reaction is carried out at a temperature of 60-80°C for 6-24 hours.

[0012] Preferably, step S1 further includes: cooling to room temperature after the reaction is completed, separating the organic phase, washing with water until neutral, removing the solvent under reduced pressure, and purifying by column chromatography using a mixture of petroleum ether and ethyl acetate, wherein the volume ratio of petroleum ether to ethyl acetate is (20-25):1.

[0013] Preferably, in step S2, the volume-to-mass ratio of solvent to intermediate is (5-10):1 mL / g, and the solvent is selected from acetonitrile or dichloroethane; Preferably, in step S2, the molar ratio of concentrated nitric acid to the intermediate is (5-6):1; and the molar ratio of potassium thiocyanate to the intermediate is (1-3):1.

[0014] Preferably, in step S2, concentrated nitric acid is added dropwise to the intermediate and reacted at 20-30°C for 30-60 minutes, followed by the addition of potassium thiocyanate to carry out a ring-closure reaction. The reaction temperature of the ring-closure reaction is 80-100°C and the reaction time is 4-8 hours.

[0015] Preferably, step S2 further includes: after the reaction is completed, cooling to 0°C, adjusting the pH to 7 with sodium carbonate aqueous solution, adding dichloromethane for extraction, washing the organic phase with water, drying, concentrating under reduced pressure to remove the solvent, and then purifying by column chromatography using a mixture of petroleum ether and dichloromethane, wherein the volume ratio of petroleum ether to dichloromethane is (5-6):1.

[0016] Compared with existing technologies, the beneficial effects of this invention are: 1) Shortest route: Only two steps, more than double the speed of existing routes, making it more economical and efficient.

[0017] 2) Mild conditions: No need for ultra-low temperature or high pressure.

[0018] 3) High safety: Avoids flammable Grignard reagents, as well as high-risk reagents such as diazonium salts and butyllithium, making the reaction relatively safe. Detailed Implementation

[0019] It should be noted that, unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. The terminology used herein in the specification is for the purpose of describing particular embodiments only and is not intended to limit the scope of the application. The reference to "embodiment" herein means that a particular feature, structure, or characteristic described in connection with an embodiment may be included in at least one embodiment of the application. The appearance of this phrase in various places in the specification does not necessarily refer to the same embodiment, nor is it a mutually exclusive, independent, or alternative embodiment. It is explicitly and implicitly understood by those skilled in the art that the embodiments described herein can be combined with other embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of this invention without inventive effort are within the scope of protection of this invention.

[0020] A method for synthesizing 11,11-dimethyl-11H-benzo[B]fluorene includes the following steps: S1, intermediate synthesis Under an inert atmosphere, 2-amino-3-bromonaphthalene and 2-phenylpropane-2-boronic acid pinacol ester were coupled in a mixed solvent in the presence of a catalyst and a base. The volume ratio of the mixed solvent to the mass of 2-amino-3-bromonaphthalene was (10-20):1. The coupling reaction was carried out at a temperature of 60-80°C for 6-24 hours. After the reaction was completed, the mixture was cooled to room temperature, the organic phase was separated, washed with water until neutral, the solvent was removed under reduced pressure, and purified by column chromatography using a mixture of petroleum ether and ethyl acetate to obtain the intermediate α,α-dimethyl-2-(2-naphthyl)-phenylmethylamine. S2, Product Synthesis A solvent was added to the intermediate at a volume-to-mass ratio of (5-10):1 mL / g. Concentrated nitric acid was added dropwise, and the mixture was reacted at 20-30°C for 30-60 minutes. Subsequently, potassium thiocyanate was added to carry out a ring-closure reaction at a temperature of 80-100°C for 4-8 hours. After the reaction was completed, the temperature was lowered to 0°C, the pH was adjusted to 7 with sodium carbonate aqueous solution, and dichloromethane was added for extraction. The organic phase was washed with water, dried, concentrated under reduced pressure to remove the solvent, and purified by column chromatography using a mixture of petroleum ether and dichloromethane to obtain 11,11-dimethyl-11H-benzo[B]fluorene.

[0021] In step S1, the mixed solvent is a mixture of toluene, water and ethanol, with a volume ratio of toluene:water:ethanol = (3-3.5):(1-1.5):1; In step S1, the palladium catalyst is selected from tetra(triphenylphosphine)palladium or bis(dibenzylacetone)palladium; the base is an inorganic base, selected from potassium carbonate or potassium hydroxide; when the palladium catalyst is bis(dibenzylacetone)palladium, a phosphine ligand needs to be added to the reaction system in step S1, and the phosphine ligand is selected from triphenylphosphine or tricyclohexylphosphine; the molar ratio of the phosphine ligand to 2-amino-3-bromonaphthalene is (0.05-0.1):1.

[0022] In step S1, the molar ratio of 2-phenylpropane-2-boronic acid pinacol ester to 2-amino-3-bromonaphthalene is (1-1.2):1; the molar ratio of the catalyst to 2-amino-3-bromonaphthalene is (0.025-0.05):1; and the molar ratio of the base to 2-amino-3-bromonaphthalene is (2-4):1.

[0023] In step S1, the volume ratio of petroleum ether to ethyl acetate is (20-25):1.

[0024] In step S2, the solvent is selected from acetonitrile or dichloroethane.

[0025] In step S2, the molar ratio of concentrated nitric acid to the intermediate is (5-6):1; the molar ratio of potassium thiocyanate to the intermediate is (1-3):1.

[0026] In step S2, the volume ratio of petroleum ether to dichloromethane is (5-6):1.

[0027] To make the objectives, technical solutions, and technical effects of this invention clearer, the technical solutions in the embodiments of this invention are now described clearly and completely. However, the embodiments described below are only some embodiments of this invention, not all embodiments. All other embodiments obtained by those skilled in the art in conjunction with the embodiments of this invention without creative effort are within the scope of protection of this invention.

[0028] Example 1: A method for synthesizing 11,11-dimethyl-11H-benzo[B]fluorene includes the following steps: 1) Intermediate synthesis In a nitrogen atmosphere, 200 mL of a mixed solvent of toluene, water, and ethanol (volume ratio 3:1:1) was added to a 500 mL four-necked flask. Then, 11.1 g (50 mmol, 1 eq) of 2-amino-3-bromonaphthalene and 12.3 g (50 mmol, 1 eq) of 2-phenylpropane-2-borate pinacol ester were added. After stirring for 10 minutes to dissolve, tetrakis(triphenylphosphine)palladium (577.8 mg, 0.5 mmol, 0.01 eq) and potassium carbonate (13.8 g, 100 mmol, 2 eq) were added to the reaction solution. The mixture was reacted at 65 °C for 6 hours. HPLC monitoring showed that the starting materials had completely reacted. The mixture was cooled to 25 °C, and the aqueous layer was separated. The organic phase was washed twice with 50 mL of deionized water. Washing was stopped after the pH of the aqueous phase was measured to be 7. 15g of silica gel was added to the organic phase, toluene was distilled off under reduced pressure, and the residue was added to a chromatography column and eluted with a mixture of petroleum ether / ethyl acetate = 20:1 (volume ratio) to give intermediate α,α-dimethyl-2-(2-naphthyl)-phenylmethylamine, mass 11.1g, yield 85.1%.

[0029] 2) Product Synthesis Add the intermediate (10.44 g, 40 mmol, 1 eq) and 100 mL of acetonitrile to a 250 mL four-necked flask and stir to dissolve. Add concentrated nitric acid (23.26 g, 240 mmol, 65 wt%, 6 eq) dropwise to the reaction solution, controlling the dropping rate and maintaining the temperature below 30 °C. After the addition is complete, stir for 30 minutes, add potassium thiocyanate (3.89 g, 35 mmol, 1 eq), and heat the reaction solution to 100 °C for 4 hours. Lower the reaction temperature to 0 °C and slowly add saturated sodium carbonate solution to the reaction solution until the pH of the aqueous phase reaches 7 to quench the reaction. Add 50 mL of dichloromethane to the reaction solution to extract the organic matter. Use 50 mL of the organic phase, wash twice with water, dry with anhydrous sodium sulfate, filter, and then evaporate to dryness. The residue after rotary evaporation was subjected to column chromatography with petroleum ether:dichloromethane in a volume ratio of 5:1 to obtain 7.30 g of 11,11-dimethyl-11H-benzo[B]fluorene with a purity of 99.8% and a yield of 74.6%.

[0030] Example 2: A method for synthesizing 11,11-dimethyl-11H-benzo[B]fluorene includes the following steps: 1) Intermediate synthesis In a nitrogen atmosphere, 200 mL of a mixed solvent of toluene, water, and ethanol (volume ratio 3:1:1) was added to a 500 mL four-necked flask. Then, 11.1 g (50 mmol, 1 eq) of 2-amino-3-bromonaphthalene and 12.3 g (50 mmol, 1 eq) of 2-phenylpropane-2-borate pinacol ester were added. After stirring for 10 minutes to dissolve, bis(dibenzylacetone)palladium (283.5 mg, 0.5 mmol, 0.01 eq), triphenylphosphine (262.2 mg, 1 mmol, 0.02 eq), and potassium carbonate (13.8 g, 100 mmol, 2 eq) were added to the reaction solution. The mixture was reacted at 65 °C for 6 hours. HPLC monitoring showed that the starting materials had completely reacted. The mixture was cooled to 25 °C, and the aqueous layer was separated. The organic phase was washed twice with 50 mL of deionized water. Washing was stopped after the pH of the aqueous phase was measured to be 7. 15g of silica gel was added to the organic phase, toluene was distilled off under reduced pressure, and the residue was added to a chromatography column and eluted with a mixture of petroleum ether / ethyl acetate = 20:1 (volume ratio) to obtain intermediate α,α-dimethyl-2-(2-naphthyl)-phenylmethylamine, mass 5.3g, yield 40.6%.

[0031] 2) Product Synthesis Add the intermediate (10.44 g, 40 mmol, 1 eq) and 100 mL of acetonitrile to a 250 mL four-necked flask and stir to dissolve. Add concentrated nitric acid (19.38 g, 200 mmol, 65 wt%, 5 eq) dropwise to the reaction solution, controlling the dropping rate, and maintain the temperature at 20-30 °C. After the addition is complete, stir for 30 minutes, add potassium thiocyanate (3.89 g, 40 mmol, 1 eq), and heat the reaction solution to 100 °C for 8 hours. Lower the reaction temperature to 0 °C, and slowly add saturated sodium carbonate solution to the reaction solution until the pH of the aqueous phase reaches 7 to quench the reaction. Add 50 mL of dichloromethane to the reaction solution to extract the organic matter. Use 50 mL of the organic phase, wash twice with water, dry with anhydrous sodium sulfate, filter, and then evaporate to dryness. The residue after rotary evaporation was subjected to column chromatography using petroleum ether:dichloromethane at a volume ratio of 5:1 to give 6.0 g of the product 11,11-dimethyl-11H-benzo[B]fluorene, with a yield of 61.3%.

[0032] Example 3: A method for synthesizing 11,11-dimethyl-11H-benzo[B]fluorene includes the following steps: 1) Intermediate synthesis Add 111 mL of a mixed solvent of toluene, water, and ethanol (volume ratio 3:1:1) to a 500 mL four-necked flask. Add 11.1 g (50 mmol, 1 eq) of 2-amino-3-bromonaphthalene and 12.3 g (50 mmol, 1 eq) of pinacol 2-phenylpropane-2-borate. Stir for 10 minutes to dissolve. Then add bis(dibenzylacetone)palladium (283.5 mg, 0.5 mmol, 0.01 eq), tricyclohexylphosphine (280.4 mg, 1 mmol, 0.02 eq), and potassium carbonate (13.8 g, 100 mmol, 2 eq) to the reaction solution. React at 65 °C for 24 hours. Cool to 25 °C, separate the aqueous layer, and wash the organic phase twice with 50 mL of deionized water. Stop washing after the pH of the aqueous phase reaches 7. 15g of silica gel was added to the organic phase, toluene was distilled off under reduced pressure, and the residue was added to a chromatography column and eluted with a mixture of petroleum ether / ethyl acetate = 20:1 (volume ratio) to give intermediate α,α-dimethyl-2-(2-naphthyl)-phenylmethylamine, mass 5.1g, yield 39.1%.

[0033] 2) Product Synthesis Add the intermediate (10.44 g, 40 mmol, 1 eq) and 60 mL of dichloroethane to a 250 mL four-necked flask and stir to dissolve. Add concentrated nitric acid (23.26 g, 240 mmol, 65 wt%, 6 eq) dropwise to the reaction solution, controlling the dropping rate and maintaining the temperature below 30 °C. After the addition is complete, stir for 30 minutes, add potassium thiocyanate (3.89 g, 40 mmol, 1 eq), and heat the reaction solution to 80 °C for 8 hours. Lower the reaction temperature to 0 °C and slowly add saturated sodium carbonate solution to the reaction solution until the pH of the aqueous phase reaches 7 to quench the reaction. Add 50 mL of dichloromethane to the reaction solution to extract the organic matter. Use 50 mL of the organic phase, wash twice with water, dry with anhydrous sodium sulfate, filter, and then evaporate to dryness. The residue after rotary evaporation was subjected to column chromatography using petroleum ether:dichloromethane at a volume ratio of 5:1 to give 7.1 g of the product 11,11-dimethyl-11H-benzo[B]fluorene, with a yield of 72.5%.

[0034] Example 4: A method for synthesizing 11,11-dimethyl-11H-benzo[B]fluorene includes the following steps: 1) Intermediate synthesis In a nitrogen atmosphere, 200 mL of a mixed solvent of toluene, water, and ethanol (volume ratio 3:1:1) was added to a 500 mL four-necked flask. Then, 11.1 g (50 mmol, 1 eq) of 2-amino-3-bromonaphthalene and 14.8 g (60 mmol, 1.2 eq) of 2-phenylpropane-2-borate pinacol ester were added. After stirring for 10 minutes to dissolve, tetrakis(triphenylphosphine)palladium (288.9 mg, 0.25 mmol, 0.025 eq) and 11.2 g (200 mmol, 2 eq) of potassium hydroxide were added to the reaction solution. The mixture was reacted at 65 °C for 6 hours. HPLC monitoring showed that the starting materials had completely reacted. The mixture was cooled to 25 °C, and the aqueous layer was separated. The organic phase was washed twice with 50 mL of deionized water. Washing was stopped after the pH of the aqueous phase was measured to be 7. 15g of silica gel was added to the organic phase, toluene was distilled off under reduced pressure, and the residue was added to a chromatography column and eluted with a mixture of petroleum ether / ethyl acetate = 20:1 (volume ratio) to give the intermediate α,α-dimethyl-2-(2-naphthyl)-phenylmethylamine, with a mass of 4.7g and a yield of 36.0%.

[0035] 2) Product Synthesis Add the intermediate (10.44 g, 40 mmol, 1 eq) and 100 mL of acetonitrile to a 250 mL four-necked flask and stir to dissolve. Add concentrated nitric acid (23.26 g, 240 mmol, 65 wt%, 6 eq) dropwise to the reaction solution, controlling the dropping rate and maintaining the temperature below 30 °C. After the addition is complete, stir for 30 minutes, add potassium thiocyanate (11.67 g, 120 mmol, 3 eq), and heat the reaction solution to 100 °C for 4 hours. Lower the reaction temperature to 0 °C and slowly add saturated sodium carbonate solution to the reaction solution until the pH of the aqueous phase reaches 7 to quench the reaction. Add 50 mL of dichloromethane to the reaction solution to extract the organic matter. Use 50 mL of the organic phase, wash twice with water, dry with anhydrous sodium sulfate, filter, and then evaporate to dryness. The residue after rotary evaporation was subjected to column chromatography using petroleum ether:dichloromethane at a volume ratio of 5:1 to give 3.7 g of the product 11,11-dimethyl-11H-benzo[B]fluorene, with a yield of 37.8%.

[0036] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and variations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A method for synthesizing 11,11-dimethyl-11H-benzo[B]fluorene, characterized in that, This includes the following two steps of reaction: S1, intermediate synthesis Under an inert atmosphere, 2-amino-3-bromonaphthalene and 2-phenylpropane-2-boronic acid pinacol ester were coupled together in a palladium catalyst, a base and a mixed solvent to give the intermediate α,α-dimethyl-2-(2-naphthyl)-phenylmethylamine. S2, Product Synthesis The intermediate underwent a cyclization reaction in a solvent in the presence of concentrated nitric acid and potassium thiocyanate to give 11,11-dimethyl-11H-benzo[B]fluorene.

2. The method for synthesizing 11,11-dimethyl-11H-benzo[B]fluorene according to claim 1, characterized in that, In step S1, the volume ratio of the mixed solvent to the mass ratio of 2-amino-3-bromonaphthalene is (10-20):1; the mixed solvent is a mixture of toluene, water and ethanol, with a volume ratio of toluene:water:ethanol = (3-3.5):(1-1.5):

1.

3. The method for synthesizing 11,11-dimethyl-11H-benzo[B]fluorene according to claim 1, characterized in that, In step S1, the palladium catalyst is selected from tetra(triphenylphosphine)palladium or bis(dibenzylacetone)palladium; the base is an inorganic base, selected from potassium carbonate or potassium hydroxide; when the palladium catalyst is bis(dibenzylacetone)palladium, a phosphine ligand needs to be added to the reaction system in step S1, and the phosphine ligand is selected from triphenylphosphine or tricyclohexylphosphine; the molar ratio of the phosphine ligand to 2-amino-3-bromonaphthalene is (0.05-0.1):

1.

4. The method for synthesizing 11,11-dimethyl-11H-benzo[B]fluorene according to claim 1, characterized in that, In step S1, the molar ratio of 2-phenylpropane-2-boronic acid pinacol ester to 2-amino-3-bromonaphthalene is (1-1.2):1; the molar ratio of the catalyst to 2-amino-3-bromonaphthalene is (0.025-0.05):1; and the molar ratio of the base to 2-amino-3-bromonaphthalene is (2-4):

1.

5. The method for synthesizing 11,11-dimethyl-11H-benzo[B]fluorene according to claim 1, characterized in that, In step S1, the coupling reaction is carried out at a temperature of 60-80°C for 6-24 hours.

6. The method for synthesizing 11,11-dimethyl-11H-benzo[B]fluorene according to claim 1, characterized in that, Step S1 also includes: cooling to room temperature after the reaction is complete, separating the organic phase, washing with water until neutral, removing the solvent under reduced pressure, and purifying by column chromatography using a mixture of petroleum ether and ethyl acetate, with a volume ratio of petroleum ether to ethyl acetate of (20-25):

1.

7. The method for synthesizing 11,11-dimethyl-11H-benzo[B]fluorene according to claim 1, characterized in that, In step S2, the volume-to-mass ratio of solvent to intermediate is (5-10):1 mL / g, and the solvent is selected from acetonitrile or dichloroethane.

8. The method for synthesizing 11,11-dimethyl-11H-benzo[B]fluorene according to claim 1, characterized in that, In step S2, the molar ratio of concentrated nitric acid to the intermediate is (5-6):1; the molar ratio of potassium thiocyanate to the intermediate is (1-3):

1.

9. The method for synthesizing 11,11-dimethyl-11H-benzo[B]fluorene according to claim 1, characterized in that, In step S2, concentrated nitric acid is added dropwise to the intermediate and reacted at 20-30℃ for 30-60 minutes. Then, potassium thiocyanate is added to carry out the ring-closure reaction. The reaction temperature of the ring-closure reaction is 80-100℃ and the reaction time is 4-8 hours.

10. The method for synthesizing 11,11-dimethyl-11H-benzo[B]fluorene according to claim 1, characterized in that, Step S2 also includes: after the reaction is completed, cooling to 0℃, adjusting the pH to 7 with sodium carbonate aqueous solution, adding dichloromethane for extraction, washing the organic phase with water, drying, concentrating under reduced pressure to remove the solvent, and then using a mixture of petroleum ether and dichloromethane for column chromatography purification, with a volume ratio of petroleum ether to dichloromethane of (5-6):1.

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