A preparation method of indanone compound

Abstract

The present application relates to the technical field of organic synthesis, and in particular to a method for preparing an indone compound, the method comprising the following steps: a nucleophilic substitution reaction between the α-carbon of a propionate and X1 of a compound of formula I to obtain a compound of formula II; the compound of formula II undergoes a Friedel-Crafts cyclization reaction to obtain an indone compound shown in formula III; X1 and X2 are independently selected from halogens. The method for preparing an indone compound of the present application shortens the reaction route to two steps, improves the preparation efficiency and total yield, uses a wider source of raw materials, is cheaper, and is more in line with the concept of green chemistry.

Description

Technical Field

[0001] The present application relates to the technical field of organic synthesis, and in particular to a method for preparing an indanone compound. Background Art

[0002] The molecule of indone compounds contains an indene ring structure formed by the fusion of a benzene ring and a five-membered ring, and has a ketone group on the five-membered ring, which can be used as an intermediate. The prepared ligand can form a complex with a transition metal (such as titanium, zirconium, hafnium, etc.) to construct a metal complex catalyst. Compared with traditional ligands, the ligands prepared by indone compounds can often more conveniently adjust the structure of the catalyst to meet the needs of preparing different materials, and can be applied to various systems such as polyethylene, polypropylene or copolymerization. At present, indone compounds have been widely used in the preparation of metallocene catalysts. Indone compounds can be used to prepare metallocene catalysts with different electronic and stereo structures, and are used to catalyze the preparation of polyolefin products with special properties.

[0003] Among the preparation methods of indanone compounds, the general preparation method is to use ortho-dihalogenated benzene compounds, diphenylacetylene compounds and carbonyl sources as raw materials, and heat them at high temperature under Pd catalysis. In the synthesis method without metal catalysis, substituted benzaldehyde or benzyl halide is usually used as raw material, and after introducing propionic acid groups and providing necessary cyclization reaction sites through step-by-step synthesis, indanone compounds are obtained through intramolecular cyclization. This type of method has a long reaction route, complicated operation, and is prone to losing part of the product in post-processing, resulting in poor overall yield.

[0004] Patent document CN108329197A discloses a method for preparing an indanone compound, comprising: 1) subjecting a compound of formula A to a condensation reaction with a compound of formula B to prepare a compound of formula C; 2) hydrolyzing the compound of formula C in the presence of a base to prepare a compound of formula D; 3) acylating and ring-closing the compound of formula D to prepare a compound of formula E:

[0005]

[0006] The preparation method of the above-mentioned indanone compounds requires three steps to complete, and the reaction route needs to be further simplified. In addition, the preparation method of the above-mentioned indanone compounds requires the use of propionate as a raw material, and the raw materials for the preparation of propionate are propionic acid and organic alcohols (such as ethanol). Since ethanol production is mainly obtained by fermentation of grains such as corn and wheat, or by using petrochemical raw materials ethylene, it is obtained by ethylene hydration, which does not conform to the current green chemistry concept. Therefore, it is necessary to develop a preparation method that avoids the use of ester compounds such as propionate. In addition, the total yield of the above-mentioned indanone compounds needs to be further improved. Summary of the invention

[0007] To solve the above problems, one or more embodiments of the present application provide a method for preparing indanone compounds, which shortens the reaction route to two steps, improves the preparation efficiency and total yield, uses raw materials from a wider source, is cheaper and is more in line with the concept of green chemistry.

[0008] The technical solution of this application includes the following contents:

[0009] A method for preparing an indanone compound comprises the following steps:

[0010] The α-carbon of the propionate undergoes a nucleophilic substitution reaction with X1 of the compound of formula I to obtain a compound of formula II;

[0011] The compound of formula II is subjected to Friedel-Crafts cyclization reaction to obtain an indanone compound of formula III;

[0012]

[0013] Wherein, X1 and X2 are independently selected from halogen.

[0014] In some embodiments, the propionate salt comprises at least one of sodium propionate and potassium propionate; and / or

[0015] X1 and X2 are Br.

[0016] In some embodiments, the α-carbon of the propionate salt undergoes a nucleophilic substitution reaction with X1 of the compound of formula I to obtain the compound of formula II, comprising:

[0017] After dissolving the propionate in a first solvent, adding an organic base at a first temperature, mixing, stirring for a first time, and then stirring for a second time at a second temperature to obtain a first solution;

[0018] At a third temperature, adding the compound of formula I to the first solution, mixing, stirring for a third time, and then stirring for a fourth time at a fourth temperature to obtain a second solution;

[0019] The second solution is post-treated to obtain the compound of formula II;

[0020] Wherein, the first solvent includes at least one of aprotic polar solvents, ether solvents and hydrocarbon solvents, the first temperature is -5°C to 5°C, the organic base includes at least one of organic lithium bases, alkali metal hydrides and amine bases, the first time is 0.5h to 1.5h, the second temperature is 20°C to 40°C, and the second time is 10h to 20h;

[0021] The third temperature is -5°C to 5°C, the third time is 20min to 40min, the fourth temperature is 20°C to 40°C, and the fourth time is 10h to 20h.

[0022] In some embodiments, the preparation method satisfies at least one of the following conditions:

[0023] (1) The weight volume ratio of the propionate and the first solvent is 9-11 g:100 mL;

[0024] (2) The molar ratio of the propionate to the organic base is 1:(0.5-1.05);

[0025] (3) The molar ratio of the propionate to the compound of formula I is 1:(0.9-1.1).

[0026] In some embodiments, the step of adding the compound of formula I to the first solution and mixing comprises:

[0027] Dissolving the compound of formula I in a second solvent to obtain a solution of the compound of formula I;

[0028] Adding the solution of the compound of formula I to the first solution in a stirring state and mixing;

[0029] Wherein, the second solvent includes at least one of aprotic polar solvents, ether solvents and hydrocarbon solvents.

[0030] In some embodiments, the second solution is post-treated to obtain the compound of formula II, comprising:

[0031] After the second solution is quenched, it is neutralized to obtain a first mixed solution with a pH value of 2 to 3;

[0032] Extracting the first mixed liquid with a first extractant, separating the organic phase, and obtaining the compound of formula II;

[0033] Wherein, the first extractant includes at least one of dichloromethane, ethyl acetate and butyl acetate.

[0034] In some embodiments, the step of quenching the second solution comprises:

[0035] At the fifth temperature, water is added to the second solution in batches and mixed until there is no temperature change in the system;

[0036] Wherein, the fifth temperature is 5°C to 15°C.

[0037] In some embodiments, the step of obtaining the compound of formula III by subjecting the compound of formula II to Friedel-Crafts cyclization reaction comprises:

[0038] dissolving a Lewis acid in a third solvent in a first protective gas to obtain a third solution;

[0039] At a sixth temperature, adding the compound of formula II to the third solution and mixing, and after the addition is complete, stirring at a seventh temperature for a fifth time to obtain a fourth solution;

[0040] The fourth solution is post-treated to obtain the compound of formula III;

[0041] Wherein, the first protective gas includes at least one of nitrogen, argon and helium, the Lewis acid includes at least one of aluminum trichloride, ferric trichloride, titanium tetrachloride and boron trifluoride, and the third solvent includes at least one of a halogenated hydrocarbon solvent, a nitro compound solvent, an ether solvent and an aromatic hydrocarbon solvent;

[0042] The sixth temperature is 5°C to 15°C, the seventh temperature is 20°C to 40°C, and the fifth time is 4h to 6h.

[0043] In some embodiments, the weight volume ratio of the Lewis acid to the third solvent is 10-15 g:100 mL; and / or

[0044] The molar ratio of the compound of formula II to the Lewis acid is 1:(1.2-1.4).

[0045] In some embodiments, the fourth solution is post-treated to obtain the compound of formula III, comprising:

[0046] After the fourth solution is quenched, a second mixed solution is obtained;

[0047] Extracting the second mixed liquid with a second extractant, separating the organic phase, and obtaining the compound of formula III;

[0048] Wherein, the second extractant includes at least one of dichloromethane, ethyl acetate and butyl acetate.

[0049] The preparation method of the indanone compound of the present application uses propionate and a compound of formula I as raw materials. The raw materials are easily available and low in cost. The overall route requires only two steps: the α-carbon of the propionate undergoes a nucleophilic substitution reaction with X1 of the compound of formula I to obtain a compound of formula II; the compound of formula II undergoes a Friedel-Crafts cyclization reaction to obtain a compound of formula III, that is, an indanone compound. The preparation method is simple and has a high overall yield, which is conducive to industrial expansion of production and application. DETAILED DESCRIPTION

[0050] The present application will be further described below in conjunction with the embodiments and examples. It should be understood that these examples are only used to illustrate the present application and are not intended to limit the scope of the present application. In addition, it should be understood that after reading the content taught in the present application, those skilled in the art may make various changes or modifications to the present application, and these equivalent forms also fall within the protection scope of the claims attached to the present application.

[0051] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which this application belongs. The terms used herein in the specification of this application are only for the purpose of describing specific embodiments and are not intended to limit this application.

[0052] the term

[0053] Unless otherwise specified or incompatible herewith, the terms and phrases used herein shall have the following meanings:

[0054] The term "and / or" used in this article includes any one of two or more related listed items, and also includes any and all combinations of related listed items, and the arbitrary and all combinations include any two related listed items, any more related listed items, or all related listed items. It should be noted that when at least three items are connected by at least two conjunctions selected from "and / or", "or / and", and "and / or", it should be understood that in this application, the technical solution undoubtedly includes technical solutions that are all connected by "logical and", and undoubtedly includes technical solutions that are all connected by "logical or". For example, "A and / or B" includes three parallel solutions of A, B and A+B.

[0055] Herein, "preferred", "preferable", "better", etc. are only used to describe implementation methods or examples with better effects. It should be understood that they do not constitute limitations on the scope of protection of this application.

[0056] In the present application, "further", "further", "particularly" and the like are used for descriptive purposes to indicate differences in content, but should not be construed as limiting the scope of protection of the present application.

[0057] In this application, the terms "first", "second", "third", "fourth", "fifth", "sixth", "seventh", etc. are used for descriptive purposes only and cannot be understood as indicating or implying relative importance or quantity, nor can they be understood as implicitly indicating the importance or quantity of the indicated technical features. Moreover, "first", "second", "third", "fourth", "fifth", "sixth", "seventh", etc. only serve the purpose of non-exhaustive enumeration and description, and it should be understood that they do not constitute a closed limitation on quantity.

[0058] In the present application, the technical features described in an open manner include closed technical solutions composed of the listed features, and also include open technical solutions containing the listed features.

[0059] In the present application, when it comes to numerical intervals (i.e., numerical ranges), unless otherwise specified, the optional numerical distribution is considered continuous within the above numerical interval, and includes the two numerical endpoints (i.e., the minimum and maximum values) of the numerical range, and each numerical value between the two numerical endpoints. Unless otherwise specified, when the numerical interval only refers to integers within the numerical interval, it includes the two endpoint integers of the numerical range, and each integer between the two endpoints. In addition, when multiple ranges are provided to describe features or characteristics, these ranges can be combined. In other words, unless otherwise specified, the ranges disclosed herein should be understood to include any and all subranges included therein.

[0060] The temperature parameters in this application, unless otherwise specified, are allowed to be either constant temperature treatment or to vary within a certain temperature range. It should be understood that the constant temperature treatment allows the temperature to fluctuate within the accuracy range controlled by the instrument. Fluctuations within the range of ±0.1°C, ±0.2°C, ±0.5°C, ±1°C, and ±2°C are allowed.

[0061] In the present application, the end point of the operation is that the system stops releasing heat, that is, when the temperature of the system no longer changes with the progress of the operation, the temperature is allowed to fluctuate within the range of ±0.1°C, ±0.2°C, and ±0.5°C. For example, in the step of quenching treatment, a quenching agent (such as water) is added to the system. During the addition process, the system will inevitably release heat. As the quenching proceeds, the heat release gradually slows down until the heat release stops, which means that the end point of the quenching is reached. It can be understood that heat release is usually a relatively obvious temperature fluctuation such as ±2°C, ±5°C, etc. When the temperature fluctuation of the system is such as ±0.1°C, ±0.2°C, and ±0.5°C, it can be considered that heat release has stopped and the end point of quenching has been reached, allowing temperature changes to be monitored over a period of time. In some embodiments, the rate of change of temperature within 5min to 10min is ±0.1°C, ±0.2°C, and ±0.5°C, which can be considered to stop releasing heat.

[0062] In the present application, weight may be μg, mg, g, kg or other mass units known in the chemical industry.

[0063] At present, the raw materials used in the preparation methods of indanone compounds do not conform to the current green chemistry concept, and raw materials from non-renewable chemical energy resources and food sources are required. In addition, the total yield of indanone compounds needs to be improved, and the route needs to be further simplified.

[0064] The present application provides a method for preparing an indanone compound, which shortens the reaction route to two steps and further improves the overall yield. The preparation method also uses cheaper and more readily available raw materials, which is conducive to industrial expansion of production and application.

[0065] The preparation method of the indanone compound of the embodiment of the present application comprises the following steps:

[0066] The α-carbon of the propionate undergoes a nucleophilic substitution reaction with X1 of the compound of formula I to obtain a compound of formula II;

[0067] The compound of formula II is subjected to Friedel-Crafts cyclization reaction to obtain an indanone compound of formula III;

[0068]

[0069] Wherein, X1 and X2 are independently selected from halogen.

[0070] In some embodiments, the propionate salt includes at least one of sodium propionate and potassium propionate.

[0071] In some embodiments, X1 and X2 are Br.

[0072] In some embodiments, the α-carbon of the propionate salt undergoes a nucleophilic substitution reaction with X1 of the compound of formula I to obtain the compound of formula II, comprising:

[0073] After dissolving the propionate in the first solvent, adding an organic base at a first temperature, mixing, stirring for a first time, and then stirring for a second time at a second temperature to obtain a first solution;

[0074] At a third temperature, adding the compound of formula I to the first solution, mixing, stirring for a third time, and then stirring for a fourth time at a fourth temperature to obtain a second solution;

[0075] The second solution is post-treated to obtain a compound of formula II;

[0076] The first solvent includes at least one of a non-protonic polar solvent, an ether solvent and a hydrocarbon solvent, the first temperature is -5°C to 5°C, the organic base includes at least one of an organic lithium base, an alkali metal hydride and an amine base, the first time is 0.5h to 1.5h, the second temperature is 20°C to 40°C, and the second time is 10h to 20h;

[0077] The third temperature is -5°C to 5°C, the third time is 20min to 40min, the fourth temperature is 20°C to 40°C, and the fourth time is 10h to 20h.

[0078] In this embodiment, after the propionate is dissolved in the first solvent, an organic base is added and mixed at a first temperature, stirred for a first time, and then stirred for a second time at a second temperature, so that the organic base can selectively capture the proton at the ortho position of the carboxyl group of the propionate and fully activate the corresponding carbon to form a carbon anion, which is beneficial to the nucleophilic substitution reaction.

[0079] In this embodiment, the compound of formula I is added to the first solution at the third temperature, the mixture is stirred for a third time, and then stirred for a fourth time at the fourth temperature, so that the nucleophilic substitution reaction is fully carried out and selectively reacts with the benzyl halogen atom X1 to avoid the formation of by-products.

[0080] In some embodiments, the first solvent is preferably an ether solvent, which can form a more stable solvation structure with the carbon anion, so that the carbon anion can effectively undergo a nucleophilic reaction with the halogen.

[0081] In this embodiment, tetrahydrofuran is further preferred because of its low toxicity, high operational safety, and greater favorability for nucleophilic reactions.

[0082] In some embodiments, the organic base is preferably an organic lithium base, which has strong alkalinity, can efficiently capture the proton of the ortho position of the carboxylic acid to form a carbon anion, and has good solubility and reactivity in the first solvent.

[0083] In this embodiment, lithium diisopropylamide is further preferred. Lithium diisopropylamide has greater steric hindrance and better selectivity. It can preferentially capture the more active protons at the ortho position of the carboxylic acid, while having less effect on protons at other positions.

[0084] In some embodiments, the weight-to-volume ratio of the propionate to the first solvent is 9-11 g:100 mL, within which the propionate can be completely dissolved to ensure smooth reaction.

[0085] In some embodiments, the molar ratio of propionate to organic base is 1:(0.5-1.05), within which the protons adjacent to the carboxylic acid of propionate can be ensured to form carbon anions without affecting other minor active protons and selectivity.

[0086] Optionally, the molar ratio of propionate to organic base can be 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1:1.0, 1:1.05, etc.

[0087] In some embodiments, the molar ratio of propionate to the compound of formula I is 1:(0.9-1.1), which can ensure that the raw materials react fully and avoid the generation of side reactions.

[0088] Alternatively, the molar ratio of propionate to the compound of formula I can be 1:0.9, 1:1, 1:1.1, etc.

[0089] In some embodiments, the step of adding the compound of formula I to the first solution and mixing comprises:

[0090] dissolving the compound of formula I in a second solvent to obtain a solution of the compound of formula I;

[0091] Add the solution of the compound of formula I to the first solution in a stirring state and mix;

[0092] The second solvent includes at least one of aprotic polar solvents, ether solvents and hydrocarbon solvents.

[0093] In some embodiments, the second solvent is preferably an ether solvent, and further preferably tetrahydrofuran, for the same reasons as the first solvent above.

[0094] In some embodiments, the second solution is post-treated to obtain a compound of formula II, comprising:

[0095] After the second solution is quenched, it is neutralized to obtain a first mixed solution with a pH value of 2 to 3;

[0096] Extracting the first mixed liquid with a first extractant, separating the organic phase, and obtaining a compound of formula II;

[0097] Wherein, the first extractant includes at least one of dichloromethane, ethyl acetate and butyl acetate.

[0098] In some embodiments, the step of quenching the second solution comprises:

[0099] At the fifth temperature, water is added to the second solution in batches and mixed until there is no temperature change in the system;

[0100] Among them, the fifth temperature is 5°C to 15°C.

[0101] In some embodiments, the step of obtaining the compound of formula III by subjecting the compound of formula II to Friedel-Crafts cyclization reaction comprises:

[0102] dissolving a Lewis acid in a third solvent in a first protective gas to obtain a third solution;

[0103] At a sixth temperature, adding the compound of formula II to the third solution and mixing, and after the addition is complete, stirring at a seventh temperature for a fifth time to obtain a fourth solution;

[0104] The fourth solution is post-treated to obtain the compound of formula III;

[0105] The first protective gas includes at least one of nitrogen, argon and helium, the Lewis acid includes at least one of aluminum trichloride, ferric trichloride, titanium tetrachloride and boron trifluoride, and the third solvent includes at least one of a halogenated hydrocarbon solvent, a nitro compound solvent, an ether solvent and an aromatic hydrocarbon solvent;

[0106] The sixth temperature is 5°C to 15°C, the seventh temperature is 20°C to 40°C, and the fifth time is 4h to 6h.

[0107] In this embodiment, the Lewis acid is dissolved in the third solvent in the first protective gas to avoid the highly active Lewis acid from reacting with water and oxygen in the air to cause deterioration, which is beneficial to maintaining the purity of the reaction system and improving the yield of the reaction.

[0108] In this embodiment, at the sixth temperature, the compound of formula II is added to the third solution and mixed. After the addition is completed, the mixture is stirred at the seventh temperature for the fifth time, which is beneficial to reduce the exothermic reaction and improve the selectivity of the reaction, so that the propionic acid group of the compound of formula II is connected to the corresponding site to form the compound of formula III, while ensuring that the reaction can proceed at a faster rate.

[0109] In some embodiments, the third solvent is preferably a halogenated hydrocarbon solvent. The halogenated alkane solvent has good solubility, including being able to fully dissolve the reactants and Lewis acid, so that the reaction system is fully mixed, which is beneficial to the reaction.

[0110] In this embodiment, dichloromethane is further preferred because it has a low boiling point and can be easily removed by distillation or the like after the reaction. For products that do not require excessive purification, the post-treatment steps can be simplified.

[0111] In some embodiments, the weight volume ratio of the Lewis acid to the third solvent is 10-15 g:100 mL.

[0112] In some embodiments, the molar ratio of the compound of formula II to the Lewis acid is 1:(1.2-1.4).

[0113] In some embodiments, the fourth solution is post-treated to obtain a compound of formula III, comprising:

[0114] After the fourth solution is quenched, a second mixed solution is obtained;

[0115] Extracting the second mixed liquid with a second extractant, separating the organic phase, and obtaining the compound of formula III;

[0116] Wherein, the second extractant includes at least one of dichloromethane, ethyl acetate and butyl acetate.

[0117] The following are some specific embodiments.

[0118] For experimental parameters not specified in the following specific embodiments, reference is made to the instructions given in the present application document, and reference may also be made to experimental manuals in the art or other experimental methods known in the art, or to experimental conditions recommended by manufacturers.

[0119] The raw materials and reagents involved in the following specific examples can be obtained from commercial sources, or can be prepared by those skilled in the art according to known methods.

[0120] Example 1

[0121] This embodiment provides a method for preparing the indanone compound of the present application, and the steps are as follows:

[0122] (1) Take a 1L multi-necked bottle, add 19.2g of sodium propionate and 200mL of tetrahydrofuran, stir until dissolved, cool to 0°C, add 100mL of lithium diisopropylamide (molar concentration is 2.0M) dropwise, and mix. During this process, the internal temperature is controlled at -5°C to 5°C. After the addition is completed, continue stirring at -5°C to 5°C for 1h, then return to room temperature of 20°C and continue stirring for 12h to obtain the first solution.

[0123] After the first solution was cooled to 0°C, 100 mL of a tetrahydrofuran solution of o-bromobenzyl bromide (molar concentration of 0.18 M) was added dropwise, stirred at 0°C for 30 min, and then returned to room temperature of 20°C and stirred overnight (10 h to 20 h) to obtain a second solution.

[0124] Add water to the second solution in batches at 5°C to 15°C for quenching until there is no temperature change in the system, then dropwise add 25 mL of concentrated hydrochloric acid for neutralization to obtain a first mixed solution with a pH value of 2 to 3;

[0125] The first mixed solution was appropriately concentrated and extracted with dichloromethane for 3 times, separated, the organic phases were combined, washed with water, and concentrated to about 50 mL to obtain a dichloromethane solution of 3-(2-bromophenyl)-2-methylpropionic acid. 1 H NMR (400 MHz, CDCl3) δ8.49 (s, 1H), 7.53 (dd, J = 17.5, 7.8 Hz, 1H), 7.36–7.17 (m, 2H), 7.09 (ddd, J = 13.0, 6.6, 3.9 Hz, 1H), 3.29–3.11 (m, 1H), 3.03–2.68 (m, 2H), 1.32–1.15 (m, 3H). The yield of 3-(2-bromophenyl)-2-methylpropanoic acid was 95% by non-separation means.

[0126] (2) Take a 1L multi-necked bottle, add nitrogen protection, add 230mL of dichloromethane and 29.4g of aluminum chloride, stir until dissolved or uniformly dispersed, and obtain a third solution. The internal temperature of the process is controlled at 5°C to 15°C.

[0127] The 3-(2-bromophenyl)-2-methylpropionic acid dichloromethane solution obtained in step (1) was added dropwise to the third solution at 5°C to 15°C. After the addition was complete, the mixture was returned to room temperature (20°C) and stirred for 5 hours to obtain a fourth solution.

[0128] After the fourth solution was quenched with water, it was extracted with dichloromethane three times, separated, the organic phases were combined, appropriately concentrated and filtered to remove impurities, and the filtrate was then spin-dried and distilled under reduced pressure to obtain 4-bromo-2-methylindanone, weighing 34 g, and the total yield of the two steps was calculated to be 85%. 1 H NMR (400MHz, CDCl3) δ7.75(dd,J=20.3,7.6Hz,2H),7.44–7.21(m,1H),3.38(dd,J=17.6,7.9Hz,1H),2.86–2.54(m,2H),1.36(d,J=7.4Hz,3H).

[0129] Example 2

[0130] This example provides a method for preparing the indanone compound of the present application, and the steps are basically the same as those of Example 1, except that 2-methyltetrahydrofuran is used in place of tetrahydrofuran in step (1). The yield of 3-(2-bromophenyl)-2-methylpropionic acid is calculated to be 93%, and the total yield is 84%.

[0131] Example 3

[0132] This example provides a method for preparing the indanone compound of the present application, the steps are basically the same as those of Example 1, except that sodium ethoxide is used in place of lithium diisopropylamide in step (1). The yield of 3-(2-bromophenyl)-2-methylpropionic acid is calculated to be 11%, and the total yield is 10%.

[0133] Example 4

[0134] This example provides a method for preparing the indanone compound of the present application, the steps are basically the same as those of Example 1, except that nitromethane is used instead of dichloromethane in step (2). The yield of 3-(2-bromophenyl)-2-methylpropionic acid is calculated to be 95%, and the total yield is 90%.

[0135] Example 5

[0136] This embodiment provides a method for preparing the indanone compound of the present application, and the steps are basically the same as those of Example 1, except that the molar ratio of the propionate to the organic base in step (1) is 1:1.5. The yield of 3-(2-bromophenyl)-2-methylpropionic acid is calculated to be 33%, and the total yield is 30%.

[0137] Example 6

[0138] This embodiment provides a method for preparing the indanone compound of the present application, and the steps are basically the same as those of Example 1, except that the molar ratio of propionate to the compound of formula I in step (1) is 1:1.5. The yield of 3-(2-bromophenyl)-2-methylpropionic acid is calculated to be 55.5%, and the total yield is 50%.

[0139] All documents mentioned in this application are cited as references in this application, just as each document is cited as reference separately. Unless they conflict with the application purpose and / or technical solution of this application, the cited documents involved in this application are cited with all contents and all purposes. When the cited documents are involved in this application, the definitions of relevant technical features, terms, nouns, phrases, etc. in the cited documents are also cited. When the cited documents are involved in this application, the examples and preferred methods of the cited relevant technical features can also be incorporated into this application as references, but are limited to the implementation of this application. It should be understood that when the cited content conflicts with the description in this application, the present application shall prevail or be modified adaptively according to the description of this application.

[0140] The technical features of the above-mentioned implementation modes and examples can be combined in any appropriate manner. To make the description concise, not all possible combinations of the technical features in the above-mentioned implementation modes and examples are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0141] The above-described embodiments only express several implementation methods of the present application, but they cannot be understood as limiting the scope of the patent application. It should be pointed out that, for those of ordinary skill in the art, without departing from the concept of the present application, several variations and improvements can also be made, which all belong to the protection scope of the present application. In addition, it should be understood that after reading the above-mentioned teaching content of the present application, those skilled in the art can make various changes or modifications to the present application, and the equivalent forms obtained also fall within the protection scope of the present application. It should also be understood that the technical solutions obtained by those skilled in the art on the basis of the technical solutions provided in the present application through logical analysis, reasoning or limited experiments are all within the protection scope of the claims attached to the present application. Therefore, the protection scope of the patent of the present application shall be based on the attached claims, and the description can be used to interpret the content of the claims.

Claims

1. A method for preparing an indanone compound, characterized in that: The steps include: The α-carbon of the propionate undergoes a nucleophilic substitution reaction with X1 of the compound of formula I to obtain a compound of formula II; The compound of formula II is subjected to Friedel-Crafts cyclization reaction to obtain an indanone compound of formula III; Wherein, X1 and X2 are independently selected from halogen.

2. The preparation method according to claim 1, characterized in that: The propionate comprises at least one of sodium propionate and potassium propionate; and / or X1 and X2 are Br.

3. The preparation method according to claim 1 or 2, characterized in that: The step of obtaining the compound of formula II by reacting the α-carbon of the propionate with X1 of the compound of formula I through a nucleophilic substitution reaction comprises: After dissolving the propionate in a first solvent, adding an organic base at a first temperature, mixing, stirring for a first time, and then stirring for a second time at a second temperature to obtain a first solution; At a third temperature, adding the compound of formula I to the first solution, mixing, stirring for a third time, and then stirring for a fourth time at a fourth temperature to obtain a second solution; The second solution is post-treated to obtain the compound of formula II; Wherein, the first solvent includes at least one of aprotic polar solvents, ether solvents and hydrocarbon solvents, the first temperature is -5°C to 5°C, the organic base includes at least one of organic lithium bases, alkali metal hydrides and amine bases, the first time is 0.5h to 1.5h, the second temperature is 20°C to 40°C, and the second time is 10h to 20h; The third temperature is -5°C to 5°C, the third time is 20min to 40min, the fourth temperature is 20°C to 40°C, and the fourth time is 10h to 20h.

4. The preparation method according to claim 3, characterized in that: At least one of the following conditions is met: (1) The weight volume ratio of the propionate and the first solvent is 9-11 g:100 mL; (2) The molar ratio of the propionate to the organic base is 1:(0.5-1.05); (3) The molar ratio of the propionate to the compound of formula I is 1:(0.9-1.1).

5. The preparation method according to claim 3, characterized in that: The step of adding the compound of formula I to the first solution and mixing comprises: Dissolving the compound of formula I in a second solvent to obtain a solution of the compound of formula I; Adding the solution of the compound of formula I to the first solution in a stirring state and mixing; Wherein, the second solvent includes at least one of aprotic polar solvents, ether solvents and hydrocarbon solvents.

6. The preparation method according to claim 3, characterized in that: The step of post-treating the second solution to obtain the compound of formula II comprises: After the second solution is quenched, it is neutralized to obtain a first mixed solution with a pH value of 2 to 3; Extracting the first mixed liquid with a first extractant, separating the organic phase, and obtaining the compound of formula II; Wherein, the first extractant includes at least one of dichloromethane, ethyl acetate and butyl acetate.

7. The preparation method according to claim 6, characterized in that: The step of quenching the second solution comprises: At the fifth temperature, water is added to the second solution in batches and mixed until there is no temperature change in the system; Wherein, the fifth temperature is 5°C to 15°C.

8. The preparation method according to claim 1 or 2, characterized in that: The step of obtaining the compound of formula III by subjecting the compound of formula II to Friedel-Crafts cyclization reaction comprises: dissolving a Lewis acid in a third solvent in a first protective gas to obtain a third solution; At a sixth temperature, adding the compound of formula II to the third solution and mixing, and after the addition is complete, stirring at a seventh temperature for a fifth time to obtain a fourth solution; The fourth solution is post-treated to obtain the compound of formula III; Wherein, the first protective gas includes at least one of nitrogen, argon and helium, the Lewis acid includes at least one of aluminum trichloride, ferric trichloride, titanium tetrachloride and boron trifluoride, and the third solvent includes at least one of a halogenated hydrocarbon solvent, a nitro compound solvent, an ether solvent and an aromatic hydrocarbon solvent; The sixth temperature is 5°C to 15°C, the seventh temperature is 20°C to 40°C, and the fifth time is 4h to 6h.

9. The preparation method according to claim 8, characterized in that: The weight volume ratio of the Lewis acid to the third solvent is 10-15 g:100 mL; and / or The molar ratio of the compound of formula II to the Lewis acid is 1:(1.2-1.4).

10. The preparation method according to claim 8, characterized in that: The step of post-treating the fourth solution to obtain the compound of formula III comprises: After the fourth solution is quenched, a second mixed solution is obtained; Extracting the second mixed liquid with a second extractant, separating the organic phase, and obtaining the compound of formula III; Wherein, the second extractant includes at least one of dichloromethane, ethyl acetate and butyl acetate.

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