CN109265431B - Synthesis process of 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromen-8 (9H) -one - Google Patents
Synthesis process of 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromen-8 (9H) -one Download PDFInfo
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Abstract
The invention provides a synthesis process of 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromene-8 (9H) -ketone, which does not use allyl trimethylsilane, and is prepared by firstly carrying out ketone protection on raw materials, synthesizing the raw materials required by the next step by using a one-pot method, and carrying out three-step reaction. The method has the advantages that the activity of reactants is increased, the reaction yield is improved, the consumption of palladium catalyst is reduced, the cost is greatly reduced, the purification process is simplified, and the product quality is improved by protecting the ketone.
Description
Technical Field
The invention relates to a synthesis process of 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromene-8 (9H) -ketone, in particular to a new process for improving the yield and purity of a product and reducing the cost by a ketone protection method.
Background
3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromen-8 (9H) -one is an important intermediate used as an antiviral drug for the treatment of hepatitis C. At present, the following two methods are used for synthesizing the compound:
the method comprises the following steps: in the patent application with the application number of WO2013/75029, 4-bromo-2- (bromomethyl) -1-chlorobenzene and 7-hydroxy-3, 4-dihydro-2H-1-naphthalenone are used as raw materials to prepare 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromen-8 (9H) -one by adopting the following reaction formula.
The disadvantages are as follows:
1) the boiling point of the trimethylacetylene is low, the selection of a factory production reaction kettle has great limitation, and the method is not suitable for industrial production;
2) the palladium catalyst is used in both steps, so that the raw material cost is high, and the method is not suitable for industrial production;
3) the method of silica gel chromatography purification used in the product refining is not suitable for industrial amplification;
the second method comprises the following steps: in the patent application with application number US2015/0361073, 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromen-8 (9H) -one is prepared from 1- (4-bromo-3-bromomethyl) phenyl) ethanone and 7-hydroxy-3, 4-dihydro-2H-1-naphthalenone as starting materials using the following reaction scheme.
Its disadvantages are the following:
(1) the used palladium catalyst has high market price, the dosage of the palladium catalyst reaches 5.0mol percent, the cost ratio is high, and the application of the palladium catalyst in the industry is limited;
(2) the silica gel chromatographic purification method used in the product refining is not suitable for industrial scale-up.
Disclosure of Invention
The invention aims to provide a synthesis process of 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromene-8 (9H) -ketone, which solves the problems of high cost (catalyst is one of main cost sources), low product yield, difficult purification and the like in the prior art for preparing the 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromene-8 (9H) -ketone.
A process for synthesizing 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromen-8 (9H) -one comprises the following steps:
step (1): using an acidic substance 1 as a catalyst and in the presence of trimethoxymethane to react 7-hydroxy-3, 4-dihydro-2H-1-naphthalenone with ethylene glycol to generate 3, 4-dihydro-2H-spiro (1,2' - [1,3] dioxolane) -7-naphthol, taking an alkaline substance 1 as a catalyst, and carrying out SN2 nucleophilic substitution reaction on 3, 4-dihydro-2H-spiro (1,2'- [1,3] dioxolane) -7-naphthol and 1- (4-bromo-3-bromomethyl) phenyl) ethanone to obtain 1- (4-bromo-3- (((3, 4-dihydro-2H-spiro [1,2' - [1,3] dioxolane ] -7-naphthyl) oxy) methyl) phenyl) ethanone;
step (2): reacting the 1- (4-bromo-3- (((3, 4-dihydro-2H-spiro [1,2'- [1,3] dioxolane ] -7-naphthyl) oxy) methyl) phenyl) ethanone obtained in the step (1) in the presence of an alkaline substance 2 under the catalysis of a palladium catalyst and a ligand to obtain 1- (10, 11-dihydro-5H, 9H-spiro [ dibenzo [ C, G ] chromene-8, 2' - [1,3] dioxolane ] -3-yl) ethanone;
and (3): and (3) removing the glycol protection of the 1- (10, 11-dihydro-5H, 9H-spiro [ dibenzo [ C, G ] chromene-8, 2' - [1,3] dioxolane ] -3-yl) ethanone obtained in the step (2) under the catalysis of an acid substance 2 to obtain 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromene-8 (9H) -one.
Further, the molar ratio of the 7-hydroxy-3, 4-dihydro-2H-1-naphthalenone to the 1- (4-bromo-3-bromomethyl) phenyl) ethanone in the step (1) is (0.05-0.5): 1.
further, the acidic substance 1 selected in the step (1) is one or more selected from n-butyl ammonium tribromide, pyridinium tribromide, hydrochloric acid, sulfuric acid, phosphoric acid and hydrobromic acid, and the mass ratio of the acidic substance to the 7-hydroxy-3, 4-dihydro-2H-1-naphthalenone is as follows: (0.05-0.15): 1.
further, the molar ratio of trimethoxymethane to 7-hydroxy-3, 4-dihydro-2H-1-naphthalenone in the step (1) is (1.0-5.0): 1.
further, the alkaline substance 1 in the step (1) is selected from one or more of sodium hydroxide, lithium hydroxide, potassium carbonate, potassium bicarbonate, sodium carbonate, sodium bicarbonate and cesium carbonate, and the molar ratio of the alkaline substance to the 1- (4-bromo-3-bromomethyl) phenyl) ethanone is (1-10): 1.
further, the step (1) is carried out in a solvent system, and the solvent is one or a mixture of several of the following solvents: organic alcohol solvent, organic amide solvent, organic ether solvent and acetonitrile.
Further, the palladium catalyst and the ligand in the step (2) are selected from one or a mixture of several of the following: palladium acetate, palladium chloride, tetratriphenylphosphine palladium, [1,1 '-bis (triphenylphosphine) ferrocene ] palladium dichloride dichloromethane complex and bistriphenylphosphine palladium dichloride, wherein the molar ratio of the palladium catalyst and the ligand thereof to 1- (4-bromo-3- (((3, 4-dihydro-2H-spiro [1,2' - [1,3] dioxolane ] -7-naphthyl) oxy) methyl) phenyl) ethanone is (0.0015-0.005): 1.
further, the alkaline substance 2 in the step (2) is selected from one or more of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium phosphate, dipotassium hydrogen phosphate and cesium carbonate, and the molar ratio of the substance to the 1- (4-bromo-3- (((3, 4-dihydro-2H-spiro [1,2' - [1,3] dioxolane ] -7-naphthyl) oxy) methyl) phenyl) ethanone is (0.5-10): 1.
further, the solvent in the step (2) is an organic amide solvent, and the organic amide solvent is one or more mixed solvents selected from the following solvents: n, N-dimethylacetamide and N, N-dimethylformamide.
Further, the acidic substance 2 in the step (3) is selected from one or more of hydrochloric acid, sulfuric acid, methanesulfonic acid, hydrobromic acid, phosphoric acid, sulfurous acid and hydrofluoric acid, and the molar ratio of the acidic substance 2 to 1- (10, 11-dihydro-5H, 9H-spiro [ dibenzo [ C, G ] chromene-8, 2' - [1,3] dioxolane ] -3-yl) ethanone is (0.1-10): 1.
compared with the prior art, the invention has the following remarkable characteristics:
(1) according to the synthetic route, the raw materials are subjected to ketone protection, and the raw materials required in the next step are synthesized by using a one-pot method, so that the separation of intermediates is reduced, the production efficiency is improved, the three wastes are reduced, and the industrial production is facilitated;
(2) in the synthesis step, special equipment such as an autoclave is not needed, and the reaction conditions are not severe;
(3) the used catalyst is reduced from 5 mol% in the literature to 0.15 mol%, and the cost is obviously reduced;
(4) the silica gel chromatographic purification used in the product refining is avoided, and the method is suitable for industrial production;
(5) the product quality is greatly improved.
Drawings
FIG. 1 is a 1H NMR chart of the final product of the present invention, 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromen-8 (9H) -one.
Detailed Description
The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. Any modifications that can be easily made by a person skilled in the art to the present invention without departing from the technical solutions of the present invention will fall within the scope of the claims of the present invention.
The present invention achieves the technical object by the following process.
According to one embodiment of the present invention, there is provided a process for the synthesis of 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromen-8 (9H) -one according to the reaction scheme:
the method specifically comprises the following steps:
step (1): an acidic substance is used as a catalyst, and 7-hydroxy-3, 4-dihydro-2H-1-naphthalenone which is used as a raw material reacts with ethylene glycol to generate a compound 3, 4-dihydro-2H-spiro (1,2' - [1,3] dioxolane) -7-naphthol which is not reported yet. Taking an alkaline substance as a catalyst, and carrying out SN2 nucleophilic substitution reaction on 3, 4-dihydro-2H-spiro (1,2'- [1,3] dioxolane) -7-naphthol and 1- (4-bromo-3-bromomethyl) phenyl) ethanone to obtain 1- (4-bromo-3- (((3, 4-dihydro-2H-spiro [1,2' - [1,3] dioxolane ] -7-naphthyl) oxy) methyl) phenyl) ethanone, wherein the product is firstly extracted, the reaction and purification are simple, the product yield is high, and an intermediate does not need to be separated and purified, and the one-pot reaction is suitable for industrial production;
step (2): reacting 1- (4-bromo-3- (((3, 4-dihydro-2H-spiro [1,2'- [1,3] dioxolan ] -7-naphthyl) oxy) methyl) phenyl) ethanone obtained in the step (1) in the presence of a palladium catalyst and a ligand in the presence of an alkaline substance to obtain 1- (10, 11-dihydro-5H, 9H-spiro [ dibenzo [ C, G ] chromene-8, 2' - [1,3] dioxolan ] -3-yl) ethanone. The product is firstly extracted, the catalyst consumption is greatly reduced compared with the known synthesis method, the reaction cost is low, the reaction rate is high, the solubility is good, the purification is easy, and the method is suitable for industrial production.
And (3): and (3) removing the glycol protection of the 1- (10, 11-dihydro-5H, 9H-spiro [ dibenzo [ C, G ] chromene-8, 2' - [1,3] dioxolane-3-yl) ethanone obtained in the step (2) under the catalysis of an acid substance to obtain 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromene-8 (9H) -one.
According to one embodiment of the present invention, there is provided a process for synthesizing 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromen-8 (9H) -one, wherein the molar ratio of 7-hydroxy-3, 4-dihydro-2H-1-naphthalenone to 1- (4-bromo-3-bromomethyl) phenyl) ethanone in the step (1) is (0.05-0.5): 1.
according to an embodiment of the present invention, there is provided a process for synthesizing 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromen-8 (9H) -one, wherein the molar ratio of trimethoxymethane to 7-hydroxy-3, 4-dihydro-2H-1-naphthalenone in the step (1) is (1.0-5.0): 1.
According to an embodiment of the invention, a process for synthesizing 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromen-8 (9H) -one is provided, wherein the mass ratio of n-butyl ammonium tribromide to 7-hydroxy-3, 4-dihydro-2H-1-naphthalenone in the step (1) is as follows: (0.05-0.15): 1.
according to one embodiment of the present invention, there is provided a process for synthesizing 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromen-8 (9H) -one, wherein the acidic substance selected in step (1) includes, but is not limited to, the following: n-butyl ammonium tribromide, pyridinium tribromide, hydrochloric acid, sulfuric acid, phosphoric acid and hydrobromic acid.
According to an embodiment of the present invention, there is provided a process for synthesizing 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromen-8 (9H) -one, wherein, when step (1) is performed in a solvent system, the solvent is one or more selected from the following solvents: organic alcohol solvent, organic amide solvent, organic ether solvent and acetonitrile.
According to an embodiment of the present invention, there is provided a process for synthesizing 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromen-8 (9H) -one, wherein the organic alcohol solvent in step (1) includes, but is not limited to, methanol, ethanol, isopropanol, n-butanol, etc.; the organic amide solvents in the step (1) include, but are not limited to, N-dimethylacetamide and N, N-dimethylformamide; the organic ether solvent is diethyl ether, isopropyl ether or tetrahydrofuran.
According to an embodiment of the invention, a synthesis process of 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromen-8 (9H) -ketone is provided, wherein the alkaline substance in the step (1) is selected from one or more of sodium hydroxide, lithium hydroxide, potassium carbonate, potassium bicarbonate, sodium carbonate, sodium bicarbonate and cesium carbonate, and the molar ratio of the alkaline substance to 1- (4-bromo-3-bromomethyl) phenyl) ethanone is (1-10): 1. that is, the kind of the basic substance and the molar ratio thereof to 1- (4-bromo-3-bromomethyl) phenyl) ethanone are not particularly limited as long as an appropriate basic reaction environment can be provided.
According to an embodiment of the present invention, there is provided a process for synthesizing 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromen-8 (9H) -one, wherein the palladium catalyst and ligand in step (2) are not limited to one or a mixture of several of the following: palladium acetate, palladium chloride, tetratriphenylphosphine palladium, [1,1 '-bis (triphenylphosphine) ferrocene ] palladium dichloride dichloromethane complex, and bistriphenylphosphine palladium dichloride, wherein the molar ratio of the palladium catalyst and the ligand thereof to 1- (4-bromo-3- (((3, 4-dihydro-2H-spiro [1,2' - [1,3] dioxolane ] -7-naphthyl) oxy) methyl) phenyl) ethanone is (0.0015-0.005): 1. that is, the molar ratio of the kind of the palladium-based catalyst and the ligand to the 1- (4-bromo-3- (((3, 4-dihydro-2H-spiro [1,2' - [1,3] dioxolan ] -7-naphthyl) oxy) methyl) phenyl) ethanone is not particularly limited as long as the catalytic effect provided by the palladium as the catalyst and the ligand can be used.
According to an embodiment of the present invention, there is provided a process for synthesizing 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromen-8 (9H) -one, wherein the basic substance in the step (2) is one or more selected from sodium hydroxide, potassium hydroxide, sodium carbonate, potassium phosphate, dipotassium hydrogen phosphate and cesium carbonate, and the molar ratio of the substance to 1- (4-bromo-3- (((3, 4-dihydro-2H-spiro [1,2' - [1,3] dioxolane ] -7-naphthyl) oxy) methyl) phenyl) ethanone is (0.5-10): 1. that is, the kind of the substance and the molar ratio thereof to 1- (4-bromo-3- (((3, 4-dihydro-2H-spiro [1,2' - [1,3] dioxolan ] -7-naphthyl) oxy) methyl) phenyl) ethanone are not particularly limited as long as an appropriate basic reaction environment can be provided.
According to an embodiment of the present invention, a synthesis process of 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromen-8 (9H) -one is provided, wherein the solvent in step (2) is an organic amide, and the organic amide solvent is one or more mixed solvents selected from the following: n, N-dimethylacetamide and N, N-dimethylformamide.
According to an embodiment of the present invention, there is provided a process for synthesizing 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromen-8 (9H) -one, wherein the acidic substance in step (3) is selected from one or more of hydrochloric acid, sulfuric acid, methanesulfonic acid, hydrobromic acid, phosphoric acid, sulfurous acid and hydrofluoric acid, and the molar ratio of the acidic substance to 1- (10, 11-dihydro-5H, 9H-spiro [ dibenzo [ C, G ] chromen-8, 2' - [1,3] dioxolan-3-yl) ethanone is (0.1-10): 1, preferably (2-4): 1. that is, the kind of the substance and the molar ratio thereof to 1- (10, 11-dihydro-5H, 9H-spiro [ dibenzo [ C, G ] chromene-8, 2' - [1,3] dioxolan ] -3-yl) ethanone are not particularly limited as long as an acidic reaction environment can be provided.
Example 1
The method comprises the following steps: (1): preparation of 1- (4-bromo-3- (((3, 4-dihydro-2H-spiro [1,2' - [1,3] dioxolan ] -7-naphthalenyl) oxy) methyl) phenyl) ethanone
(1) Synthesis example 1 of 1- (4-bromo-3- (((3, 4-dihydro-2H-spiro [1,2' - [1,3] dioxolan ] -7-naphthyl) oxy) methyl) phenyl) ethanone
29.1g (0.179mol) of 7-hydroxy-3, 4-dihydro-2H-1-naphthalenone, 100mL of ethylene glycol, 25.3g (0.238mol) of trimethoxymethane and 2.91g (10% by weight) of n-butyl tribromide were charged into a 3L three-necked flask equipped with a magnetic stirrer at room temperature. After completion of the addition, stirring was continued at room temperature for 1 hour, and then 28.4g (0.206mol) of potassium carbonate, 50g (0.171mol) of 1- (4-bromo-3- (bromomethyl) phenyl) ethan-1-one and 100mL of ethanol were added, and the temperature was raised to 50 ℃ to react for 3 hours. The reaction was cooled to 25 ℃, water and ethyl acetate were added in sequence, the layers were separated and the organic phase was concentrated to give 69.6g of a white solid in 93.2% yield. 1HNMR (DMSO-d6, 400MHz) delta ppm8.14(s,1H), 7.85-7.86(d, 2H), 7.04-7.07(d, 1H), 7.00-7.01(d, 1H), 6.95-6.97(d, 1H), 5.17(s, 2H), 4.01-4.11(m, 4H), 2.65-2.68(t, 2H), 2.59(s, 3H), 1.81-1.83(m, 4H).
(2) Synthesis example 2 of 1- (4-bromo-3- (((3, 4-dihydro-2H-spiro [1,2' - [1,3] dioxolan ] -7-naphthyl) oxy) methyl) phenyl) ethanone
To a 3L three-necked flask equipped with a magnetic stirring apparatus were charged 29.1g (0.179mol) of 7-hydroxy-3, 4-dihydro-2H-1-naphthalenone, 100mL of ethylene glycol, 25.3g (0.238mol) of trimethoxymethane and 2.91g (10 wt%) of tribromopyridinium at room temperature. After completion of the addition, stirring was continued at room temperature for 1 hour, and then 28.4g (0.206mol) of potassium carbonate, 50g (0.171mol) of 1- (4-bromo-3- (bromomethyl) phenyl) ethan-1-one and 100mL of ethanol were added, and the temperature was raised to 50 ℃ to react for 3 hours. The reaction was cooled to 25 ℃ and water and ethyl acetate were added in order, the layers separated and the organic phase concentrated to give 68.3g of a white solid (theoretical 71.3g) in 91.5% yield. 1HNMR (DMSO-d6, 400MHz) delta ppm8.14(s,1H), 7.85-7.86(d, 2H), 7.04-7.07(d, 1H), 7.00-7.01(d, 1H), 6.95-6.97(d, 1H), 5.17(s, 2H), 4.01-4.11(m, 4H), 2.65-2.68(t, 2H), 2.59(s, 3H), 1.81-1.83(m, 4H).
Step (2): preparation of 1- (10, 11-dihydro-5H, 9H-spiro [ dibenzo [ C, G ] chromene-8, 2' - [1,3] dioxolan-3-yl) ethanone Synthesis example 1
To a 250mL three-necked flask equipped with a magnetic stirrer were added 10g (24.03mmol) of 1- (4-bromo-3- (((3, 4-dihydro-2H-spiro [1,2' - [1,3] dioxolan ] -7-naphthyl) oxy) methyl) phenyl) ethanone, 6.7g (48.6mmol) of potassium carbonate, 8.09mg (0.15 mol%) of palladium acetate, 9.46mg (0.15 mol%) of triphenylphosphine, 0.735g (7.21mmol) of pivalic acid, and 100mL of N, N-dimethylformamide, and the mixture was stirred while warming to 85 ℃ for 10H while displacing nitrogen. After the reaction, the temperature was reduced to 25 ℃ and water and ethyl acetate were sequentially added to separate the liquids, and the organic phase was concentrated to give 7.6g of a pale yellow solid (theoretical amount: 8.06g), with a yield of 94.5%. 1HNMR (DMSO-d6, 400MHz) delta ppm7.95-7.99(d,2H), 7.89(s, 1H), 7.71(s, 1H), 7.00(s, 1H), 5.17(s, 1H), 4.01-4.13(m, 4H), 2.77(m, 2H), 2.60(s, 3H), 1.85-1.87(m, 4H).
And (3): synthesis example 1 for preparation of 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromen-8 (9H) -one
10G (34.21mmol) of 1- (10, 11-dihydro-5H, 9H-spiro [ dibenzo [ C, G ] chromene-8, 2' - [1,3] dioxolan ] -3-yl) ethanone and 100mL of dichloromethane are added to a single-neck flask equipped with a magnetic stirrer, 50mL of 2mol/L aqueous hydrochloric acid are added dropwise at 20-25 ℃, stirred for 5 hours, saturated sodium bicarbonate is added to neutralize the pH to 7-8, the aqueous phase is separated, extracted with dichloromethane, the organic phase is combined and then concentrated to give 8.26G of a pale yellow solid (theoretical 8.69G), yield 95.1%. 1HNMR (DMSO-d6, 400MHz) delta ppm8.06-8.08 (d,1H), 7.99-8.02(dd, 1H), 7.93(s, 1H), 7.38(s, 1H), 5.24 (s, 2H), 2.96-2.98(t, 2H), 2.60-2.62(m, 5H), 2.03-2.09(d, 2H).
The method for preparing the 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromene-8 (9H) -ketone has the advantages of simple process, low requirement on production conditions, easy product purification, high yield and lower cost compared with the known method, and obviously improves the production efficiency and the product quality of the 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromene-8 (9H) -ketone.
The method for preparing the 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromene-8 (9H) -ketone has the advantages of simple process, low requirements on production conditions, low cost, easy product purification and high yield, and remarkably improves the production efficiency of the 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromene-8 (9H) -ketone. The invention has repeated the experimental steps of the original patent US2015/0361073, the effective content of the obtained product is only 65%, while the effective content of the product obtained by the process of the invention is more than 92%, the product quality is greatly improved, and the invention is greatly helpful for the next reaction and purification.
Claims (10)
1. A process for synthesizing 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromen-8 (9H) -one comprises the following steps:
step (1): using an acidic substance 1 as a catalyst and in the presence of trimethoxymethane to react 7-hydroxy-3, 4-dihydro-2H-1-naphthalenone with ethylene glycol to generate 3, 4-dihydro-2H-spiro (1,2' - [1,3] dioxolane) -7-naphthol, taking an alkaline substance 1 as a catalyst, and carrying out SN2 nucleophilic substitution reaction on 3, 4-dihydro-2H-spiro (1,2'- [1,3] dioxolane) -7-naphthol and 1- (4-bromo-3-bromomethyl) phenyl) ethanone to obtain 1- (4-bromo-3- (((3, 4-dihydro-2H-spiro [1,2' - [1,3] dioxolane ] -7-naphthyl) oxy) methyl) phenyl) ethanone;
step (2): reacting the 1- (4-bromo-3- (((3, 4-dihydro-2H-spiro [1,2'- [1,3] dioxolane ] -7-naphthyl) oxy) methyl) phenyl) ethanone obtained in the step (1) in the presence of an alkaline substance 2 under the catalysis of a palladium catalyst and a ligand to obtain 1- (10, 11-dihydro-5H, 9H-spiro [ dibenzo [ C, G ] chromene-8, 2' - [1,3] dioxolane ] -3-yl) ethanone;
and (3): and (3) removing the glycol protection of the 1- (10, 11-dihydro-5H, 9H-spiro [ dibenzo [ C, G ] chromene-8, 2' - [1,3] dioxolane ] -3-yl) ethanone obtained in the step (2) under the catalysis of an acid substance 2 to obtain 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromene-8 (9H) -one.
2. The process for the synthesis of 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromen-8 (9H) -one according to claim 1, wherein: in the step (1), the molar ratio of the 7-hydroxy-3, 4-dihydro-2H-1-naphthalenone to the 1- (4-bromo-3-bromomethyl) phenyl) ethanone is (0.05-0.5): 1.
3. the process for the synthesis of 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromen-8 (9H) -one according to claim 1, wherein: the acidic substance 1 selected in the step (1) is one or more selected from n-butyl ammonium tribromide, pyridinium tribromide, hydrochloric acid, sulfuric acid, phosphoric acid and hydrobromic acid, and the mass ratio of the acidic substance to the 7-hydroxy-3, 4-dihydro-2H-1-naphthalenone is as follows: (0.05-0.15): 1.
4. the process for the synthesis of 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromen-8 (9H) -one according to claim 1, wherein: the molar ratio of trimethoxymethane to 7-hydroxy-3, 4-dihydro-2H-1-naphthalenone in the step (1) is (1.0-5.0): 1.
5. the process for the synthesis of 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromen-8 (9H) -one according to claim 1, wherein: the alkaline substance 1 in the step (1) is selected from one or more of sodium hydroxide, lithium hydroxide, potassium carbonate, potassium bicarbonate, sodium carbonate, sodium bicarbonate and cesium carbonate, and the molar ratio of the alkaline substance to the 1- (4-bromo-3-bromomethyl) phenyl) ethanone is (1-10): 1.
6. the process for the synthesis of 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromen-8 (9H) -one according to claim 1, wherein: the step (1) is carried out in a solvent system, and the solvent is one or a mixture of several of the following solvents: organic alcohol solvent, organic amide solvent, organic ether solvent and acetonitrile.
7. The process for the synthesis of 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromen-8 (9H) -one according to claim 1, wherein: the palladium catalyst and the ligand in the step (2) are selected from one or a mixture of more of the following: tetratriphenylphosphine palladium, [1,1 '-bis (diphenylphosphino) ferrocene ] palladium dichloride dichloromethane complex, and bis-triphenylphosphine palladium dichloride, wherein the molar ratio of the palladium catalyst and the ligand thereof to 1- (4-bromo-3- (((3, 4-dihydro-2H-spiro [1,2' - [1,3] dioxolane ] -7-naphthyl) oxy) methyl) phenyl) ethanone is (0.0015-0.005): 1.
8. the process for the synthesis of 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromen-8 (9H) -one according to claim 1, wherein: the alkaline substance 2 in the step (2) is selected from one or more of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium phosphate, dipotassium hydrogen phosphate and cesium carbonate, and the molar ratio of the substance to 1- (4-bromo-3- (((3, 4-dihydro-2H-spiro [1,2' - [1,3] dioxolane ] -7-naphthyl) oxy) methyl) phenyl) ethanone is (0.5-10): 1.
9. the process for the synthesis of 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromen-8 (9H) -one according to claim 1, wherein: the solvent in the step (2) is organic amide, and the organic amide solvent is one or more mixed solvents selected from the following solvents: n, N-dimethylacetamide and N, N-dimethylformamide.
10. The process for the synthesis of 3-acetyl-10, 11-dihydro-5H-dibenzo [ C, G ] chromen-8 (9H) -one according to claim 1, wherein: the acidic substance 2 in the step (3) is selected from one or more of hydrochloric acid, sulfuric acid, methanesulfonic acid, hydrobromic acid, phosphoric acid, sulfurous acid and hydrofluoric acid, and the molar ratio of the acidic substance 2 to 1- (10, 11-dihydro-5H, 9H-spiro [ dibenzo [ C, G ] chromene-8, 2' - [1,3] dioxolane ] -3-yl) ethanone is (0.1-10): 1.
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