Preparation method of 2-amino-1-(4-isopropoxy-2-methylphenyl)-2-methylpropane-1-ketone

Abstract

The invention discloses a preparation method of 2-amino-1-(4-isopropoxy-2-methylphenyl)-2-methylpropane-1-ketone, which comprises the following specific implementation processes: taking m-methylphenol as a raw material, and carrying out etherification, bromination, Grignard reaction and acidolysis processes to prepare a target product, namely the 2-amino-1-(4-isopropoxy-2-methylphenyl)-2-methylpropane-1-ketone. The reaction process is as follows: the substituent group R in the # imgabs0 # compound as shown in the formula (V) is methoxy, ethyoxyl, phenoxyl, benzyloxyl or methoxy (methyl) amino. According to the invention, the cost of the reaction raw materials is low, the reaction steps are few, and the 2-amino-1-(4-isopropoxy-2-methylphenyl)-2-methylpropane-1-ketone is efficiently synthesized.

Description

Technical Field

[0001] The invention belongs to the technical field of organic chemical synthesis, and specifically relates to a preparation method of 2-amino-1-(4-isopropoxy-2-methylphenyl)-2-methylpropane-1-one. Background Art

[0002] Isopropylthiocarbamide, chemical name is N-(1-(4-isopropoxy-2-methylphenyl)-2-methyl-1-oxopropan-2-yl)-3-methylthiophene-2-carboxamide, and its structural formula is:

[0003]

[0004] Isoprofen is an emerging high-efficiency organic sulfur fungicide with the characteristics of broad spectrum, high efficiency and safety. It is a type of succinate dehydrogenase inhibitor (SDHI) with a thiophene amide structure. It completely or partially occupies the site of the substrate ubiquinone, inhibits electron transfer, blocks the energy metabolism of pathogens, inhibits growth and causes death. It can effectively prevent and control a variety of diseases, such as tomato early blight, cucumber downy mildew, beet ring spot, etc. Isoprofen has a short residence time on plants and will not pollute the soil or the environment.

[0005] The synthesis method of the isopropylthiocarbamide intermediate 2-amino-1-(4-isopropoxy-2-methylphenyl)-2-methylpropane-1-one reported in the literature mainly includes:

[0006] 1. Ishihara Sangyio Kaisha, Ltd. disclosed isoprenaline in PCT patent applications WO 2003 / 027059 and WO 2006 / 016708. Patents WO 2003 / 027059 and WO 2006 / 016708 describe methods for preparing isoprenaline, including a method for synthesizing 2-amino-1-(4-isopropoxy-2-methylphenyl)-2-methylpropane-1-one, an intermediate of isoprenaline; Patents WO 2003 / 027059 and WO 2006 / 016708 use bromide A as a raw material to prepare keto compound C through substitution and oxidation. In addition, the patents disclose three methods for preparing compound D: direct amination reaction with ammonia gas; azidation followed by reduction; and preparation of ammonium salt followed by cyclization and final ring opening.

[0007]

[0008] 2. Patent CN 118159518A uses 1-bromo-4-isopropoxy-2-toluene as the starting material, and prepares 2-amino-1-(4-isopropoxy-2-methylphenyl)-2-methylpropane-1-one through Grignard reaction, cyano addition, hydrolysis, bromination, nitration, and reduction. The reaction steps are lengthy, and the reaction process involves hazardous raw materials such as nitrite and iron powder.

[0009]

[0010] 3. Patent CN112745260A discloses a method for preparing 2-amino-1-(4-isopropoxy-2-methylphenyl)-2-methylpropane-1-one using 4-isopropoxy-2-methylphenylisobutyl ketone as a raw material through bromination, azidation and reduction. The method involves the risk of explosion of azide in industrial production. Summary of the invention

[0011] In view of the above problems, the object of the present invention is to provide a method for preparing 2-amino-1-(4-isopropoxy-2-methylphenyl)-2-methylpropane-1-one.

[0012] The specific technical solutions are as follows:

[0013] A method for preparing 2-amino-1-(4-isopropoxy-2-methylphenyl)-2-methylpropane-1-one comprises the following steps:

[0014] 1) Etherification reaction: dissolving the compound represented by formula (I) and 2-bromopropane in an organic solvent A under stirring, and carrying out a heat-insulating reaction under the catalysis of a base. After the etherification reaction is completed by TLC monitoring, the reaction solution is post-treated to obtain a compound represented by formula (II);

[0015] 2) Bromination reaction: the compound represented by formula (II) reacts with N-bromosuccinimide in an organic solvent B. After the reaction is completed by TLC monitoring, the reaction solution is post-treated to obtain the compound represented by formula (III);

[0016] 3) Grignard reaction: the compound represented by formula (III) reacts with magnesium in an organic solvent C at 50° C. for 3-6 hours to obtain a compound represented by formula (IV); under stirring, the compound represented by formula (V) is dissolved in an organic solvent C, and the compound represented by formula (IV) is added. After the reaction is completed by TLC monitoring, the reaction solution is treated to obtain a compound represented by formula (VI);

[0017] 4) Acid hydrolysis reaction: dissolving the compound represented by formula (VI) in dichloromethane under stirring, adding an acidic species dropwise at 0-25° C., and after the reaction is completed by TLC monitoring, the reaction solution is treated to obtain the compound represented by formula (VII);

[0018] The reaction process is as follows:

[0019]

[0020] Wherein the substituent R in the compound represented by formula (V) is methoxy, ethoxy, phenoxy, benzyloxy or methoxy(methyl)amino.

[0021] Furthermore, the organic solvent A in step 1) is N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide or 1,4-dioxane, preferably N-methylpyrrolidone.

[0022] Furthermore, the reaction temperature of the heat preservation reaction in step 1) is 80-120°C.

[0023] Furthermore, the organic solvent B in step 2) is acetonitrile, dichloromethane or carbon tetrachloride, preferably acetonitrile.

[0024] Furthermore, the reaction temperature in step 2) is 10-30°C.

[0025] Furthermore, the organic solvent C in step 3) is a mixture of one or more of tetrahydrofuran, diethyl ether, and toluene, preferably tetrahydrofuran.

[0026] Furthermore, in step 3), the compound represented by formula (V) is dissolved in an organic solvent C, and the reaction temperature is -78 to -50°C when the compound represented by formula (IV) is added.

[0027] Furthermore, in step 3), the molar ratio of the compound represented by formula (V) to the compound represented by formula (IV) is 1:1.0 to 1:3.0.

[0028] Furthermore, the acidic species in step 4) is trifluoroacetic acid, acetic acid or hydrochloric acid, preferably trifluoroacetic acid.

[0029] The beneficial effects of the present invention are:

[0030] 1) The present invention has low cost of reaction raw materials and few reaction steps, and uses Grignard reaction to efficiently synthesize 2-amino-1-(4-isopropoxy-2-methylphenyl)-2-methylpropane-1-one;

[0031] 2) The present invention has simple operation and high yield of target product;

[0032] 3) The process of the present invention is simple, safe, efficient, economical and suitable for large-scale production. DETAILED DESCRIPTION

[0033] The present invention is further described below in conjunction with specific embodiments, but the protection scope of the present invention is not limited thereto.

[0034] Example 1

[0035] Preparation of Compound II

[0036] Add 100.0g of m-cresol, 125.1g of 2-bromopropane, and 1500mL of N,N-dimethylformamide to a 3.0L three-necked flask, add 153.0g of anhydrous potassium carbonate in batches under vigorous stirring, and heat the reaction to 120°C. During the reaction, the solution gradually turns gray. TLC monitors the reaction. When the raw materials react completely, cool the reaction system to room temperature, filter to remove the solid, wash the filtrate with water, and extract with ethyl acetate. The organic phase is dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 131.0g of colorless clear liquid 1-isopropoxy-3-toluene, with a purity of 99.0% and a yield of 95.0%.

[0037] Example 2

[0038] Preparation of Compound II

[0039] Add 100.0g of m-cresol, 125.1g of 2-bromopropane, and 1500mL of N,N-dimethylacetamide to a 3.0L three-necked flask, add 153.0g of anhydrous potassium carbonate in batches under vigorous stirring, and heat the reaction to 100°C. During the reaction, the solution gradually turns gray. TLC monitors the reaction. When the raw materials react completely, cool the reaction system to room temperature, filter to remove the solid, wash the filtrate with water, and extract with ethyl acetate. The organic phase is dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 127.6g of colorless clear liquid 1-isopropoxy-3-toluene, with a purity of 99.0% and a yield of 91.0%.

[0040] Example 3

[0041] Preparation of Compound II

[0042] 100.0g of m-cresol, 125.1g of 2-bromopropane and 1500mL of N-methylpyrrolidone were added to a 3.0L three-necked flask, and 153.0g of anhydrous potassium carbonate was added in batches under vigorous stirring. The reaction temperature was raised to 90°C. During the reaction, the solution gradually turned gray. The reaction was monitored by TLC. When the raw materials reacted completely, the reaction system was cooled to room temperature, the solid was removed by suction filtration, the filtrate was washed with water, and the liquid was separated by ethyl acetate extraction. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 120.6g of colorless clear liquid 1-isopropoxy-3-toluene with a purity of 99.0% and a yield of 87.0%.

[0043] Example 4

[0044] Preparation of Compound II

[0045] Add 100.0g of m-cresol, 125.1g of 2-bromopropane, and 1500mL of dimethyl sulfoxide to a 3.0L three-necked flask, add 153.0g of anhydrous potassium carbonate in batches under vigorous stirring, and heat the reaction to 80°C. During the reaction, the solution gradually turns gray, and TLC monitors the reaction. When the raw materials react completely, the reaction system is cooled to room temperature, the solid is removed by suction filtration, the filtrate is washed with water, and the liquid is separated by ethyl acetate extraction. The organic phase is dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 123.4g of colorless clear liquid 1-isopropoxy-3-toluene, with a purity of 99.0% and a yield of 89.0%.

[0046] Example 5

[0047] Preparation of Compound III

[0048] 150.0 g of 1-isopropoxy-3-toluene and 2000 mL of acetonitrile were added to a 3.0 L three-necked flask, and 196.0 g of N-bromosuccinimide was added in batches under vigorous stirring, and the reaction temperature was maintained at 20° C. During the reaction, the solution gradually turned yellow, and the reaction was monitored by TLC. When the raw materials reacted completely, the reaction system was cooled to room temperature, the reaction solution was concentrated under reduced pressure, washed with water, extracted with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 221.2 g of colorless clear liquid 1-bromo-4-isopropoxy-2-toluene, with a purity of 99.0% and a yield of 97.0%.

[0049] Example 6

[0050] Preparation of Compound III

[0051] To a 3.0L three-necked flask, 150.0g of 1-isopropoxy-3-toluene and 2000mL of dichloromethane were added, and 196.0g of N-bromosuccinimide was added in batches under vigorous stirring. The reaction temperature was maintained at 10°C. During the reaction, the solution gradually turned yellow. The reaction was monitored by TLC. When the raw materials were completely reacted, the reaction system was cooled to room temperature. The reaction solution was concentrated under reduced pressure, washed with water, and separated by extraction with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 214.3g of colorless clear liquid 1-bromo-4-isopropoxy-2-toluene with a purity of 99.0% and a yield of 94.0%.

[0052] Example 7

[0053] Preparation of Compound III

[0054] To a 3.0L three-necked flask, 150.0g of 1-isopropoxy-3-toluene and 2000mL of carbon tetrachloride were added, and 196.0g of N-bromosuccinimide was added in batches under vigorous stirring. The reaction temperature was maintained at 25°C. During the reaction, the solution gradually turned yellow. The reaction was monitored by TLC. When the raw materials were completely reacted, the reaction system was cooled to room temperature, the reaction solution was concentrated under reduced pressure, washed with water, and separated by extraction with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 225.7g of colorless clear liquid 1-bromo-4-isopropoxy-2-toluene with a purity of 99.0% and a yield of 99.0%.

[0055] Example 8

[0056] Preparation of Compound VI

[0057] In a nitrogen atmosphere, add 114.0g 1-bromo-4-isopropoxy-2-toluene, 12.5g magnesium, and 600mL tetrahydrofuran to a 1.0L reaction bottle, and heat to 50°C. During the reaction, the solution gradually becomes turbid, and the reaction is kept warm for 6h to obtain 600mL of tetrahydrofuran solution containing 126g of compound IV (4-isopropoxy-2-methylphenyl) magnesium bromide. Add 108.6g 2-((tert-butyloxycarbonyl)amino)-2-methylpropionic acid methyl ester and 400mL tetrahydrofuran to a 2.0L reaction bottle, keep the temperature at -60°C, and slowly add the tetrahydrofuran solution of the above compound IV. The reaction was monitored by TLC. When the raw materials reacted completely, the reaction solution was warmed to room temperature, washed with saturated aqueous ammonium chloride solution, extracted with ethyl acetate and separated. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 284.9 g of colorless clear liquid (1-(4-isopropoxy-2-methylphenyl)-2-methyl-1-oxopropan-2-yl)carbamic acid tert-butyl ester with a purity of 99.2% and a yield of 85%.

[0058] Example 9

[0059] Preparation of Compound VI

[0060] In a nitrogen atmosphere, add 114.0g 1-bromo-4-isopropoxy-2-toluene, 12.5g magnesium, and 600mL tetrahydrofuran to a 1.0L reaction bottle, and heat to 50°C. During the reaction, the solution gradually becomes turbid, and the reaction is kept warm for 5h to obtain 600mL of tetrahydrofuran solution containing 126g (4-isopropoxy-2-methylphenyl) magnesium bromide. Add 57.8g ethyl 2-((tert-butoxycarbonyl)amino)-2-methylpropanoate and 600mL ether to a 2.0L reaction bottle, keep the temperature at -78°C, and slowly add the above tetrahydrofuran solution of (4-isopropoxy-2-methylphenyl) magnesium bromide. The reaction was monitored by TLC. When the raw materials reacted completely, the reaction solution was warmed to room temperature, washed with saturated aqueous ammonium chloride solution, extracted with ethyl acetate and separated. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 62.0 g of colorless clear liquid (1-(4-isopropoxy-2-methylphenyl)-2-methyl-1-oxopropan-2-yl)carbamic acid tert-butyl ester with a purity of 99.0% and a yield of 74%.

[0061] Example 10

[0062] Preparation of Compound VI

[0063] In a nitrogen atmosphere, add 228.0g 1-bromo-4-isopropoxy-2-toluene, 25.0g magnesium, and 1000mL tetrahydrofuran to a 2.0L reaction bottle, and heat to 50°C. During the reaction, the solution gradually becomes turbid, and the reaction is kept warm for 4h to obtain 1000mL of tetrahydrofuran solution containing 252g (4-isopropoxy-2-methylphenyl) magnesium bromide. Add 93.0g 2-((tert-butyloxycarbonyl)amino)-2-methylpropionic acid phenyl ester and 800mL toluene to a 3.0L reaction bottle, keep the temperature at -50°C, and slowly add the above-mentioned tetrahydrofuran solution of (4-isopropoxy-2-methylphenyl) magnesium bromide. The reaction was monitored by TLC. When the raw materials reacted completely, the reaction solution was warmed to room temperature, washed with saturated aqueous ammonium chloride solution, extracted with ethyl acetate and separated. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 38.5 g of colorless clear liquid (1-(4-isopropoxy-2-methylphenyl)-2-methyl-1-oxopropan-2-yl)carbamic acid tert-butyl ester with a purity of 99.7% and a yield of 69%.

[0064] Embodiment 11

[0065] Preparation of Compound VI

[0066] In a nitrogen atmosphere, add 171.0g 1-bromo-4-isopropoxy-2-toluene, 18.8g magnesium, and 800mL tetrahydrofuran to a 2.0L reaction bottle, and heat to 50°C. During the reaction, the solution gradually becomes turbid, and the reaction is kept warm for 3h to obtain 800mL of tetrahydrofuran solution containing 189g (4-isopropoxy-2-methylphenyl) magnesium bromide. Add 109.9g 2-((tert-butyloxycarbonyl)amino)-2-methylpropionic acid benzyl ester, 300mL tetrahydrofuran, and 300mL ether to a 3.0L reaction bottle, keep the temperature at -60°C, and slowly add the above-mentioned tetrahydrofuran solution of (4-isopropoxy-2-methylphenyl) magnesium bromide. The reaction was monitored by TLC. When the raw materials reacted completely, the reaction solution was warmed to room temperature, washed with saturated aqueous ammonium chloride solution, extracted with ethyl acetate and separated. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 98.0 g of colorless clear liquid (1-(4-isopropoxy-2-methylphenyl)-2-methyl-1-oxopropan-2-yl)carbamic acid tert-butyl ester with a purity of 99.2% and a yield of 78%.

[0067] Example 12

[0068] Preparation of Compound VI

[0069] In a nitrogen atmosphere, add 171.0g 1-bromo-4-isopropoxy-2-toluene, 18.8g magnesium, 800mL tetrahydrofuran to a 2.0L reaction bottle, and heat to 50°C. During the reaction, the solution gradually becomes turbid, and the reaction is kept warm for 3h to obtain 800mL of tetrahydrofuran solution containing 189g (4-isopropoxy-2-methylphenyl) magnesium bromide. Add 41.0g (1-(methoxy(methyl)amino)-2-methyl-1-oxopropyl-2-yl) tert-butyl carbamate, 300mL tetrahydrofuran, and 300mL ether to a 3.0L reaction bottle, keep the temperature at -50°C, and slowly add the above-mentioned tetrahydrofuran solution of (4-isopropoxy-2-methylphenyl) magnesium bromide. The reaction was monitored by TLC. When the raw materials reacted completely, the reaction solution was warmed to room temperature, washed with saturated aqueous ammonium chloride solution, extracted with ethyl acetate and separated. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 53.1 g of colorless clear liquid (1-(4-isopropoxy-2-methylphenyl)-2-methyl-1-oxopropan-2-yl)carbamic acid tert-butyl ester with a purity of 99.2% and a yield of 95%.

[0070] Embodiment 13

[0071] Preparation of Compound VII

[0072] Add 100.0g (1-(4-isopropoxy-2-methylphenyl)-2-methyl-1-oxopropyl-2-yl) tert-butyl carbamate and 1.0L dichloromethane to a 2.0L three-necked flask, stir and dissolve at 0°C, slowly add 150.4g trifluoroacetic acid to the reaction flask, and keep the reaction temperature at 0°C. During the reaction, the solution gradually turns yellow, and the reaction is monitored by TLC. When the raw materials react completely, the reaction solution is raised to room temperature, concentrated under reduced pressure to precipitate solids, and washed with dichloromethane to obtain 80.6g of 2-amino-1-(4-isopropoxy-2-methylphenyl)-2-methylpropane-1-one as a white powder with a purity of 98.7% and a yield of 99%.

[0073] Embodiment 14

[0074] Preparation of Compound VII

[0075] Add 100.0g (1-(4-isopropoxy-2-methylphenyl)-2-methyl-1-oxopropyl-2-yl) tert-butyl carbamate and 1.0L dichloromethane to a 2.0L three-necked flask, stir and dissolve at 0°C, slowly add 79.2g acetic acid to the reaction flask, and keep the reaction temperature at 0°C. During the reaction, the solution gradually turns yellow, and the reaction is monitored by TLC. When the raw materials react completely, the reaction solution is warmed to room temperature, concentrated under reduced pressure to precipitate solids, and washed with dichloromethane to obtain 79.8g of 2-amino-1-(4-isopropoxy-2-methylphenyl)-2-methylpropane-1-one as a white powder with a purity of 99.1% and a yield of 98%.

[0076] Embodiment 15

[0077] Preparation of Compound VII

[0078] Add 100.0g (1-(4-isopropoxy-2-methylphenyl)-2-methyl-1-oxopropyl-2-yl) tert-butyl carbamate and 1.0L dichloromethane to a 2.0L three-necked flask, stir and dissolve at 0°C, slowly add 130.1g concentrated hydrochloric acid to the reaction flask, and keep the reaction temperature at 0°C. During the reaction, the solution gradually turns yellow, and the reaction is monitored by TLC. When the raw materials react completely, the reaction solution is warmed to room temperature, concentrated under reduced pressure to precipitate solids, and washed with dichloromethane to obtain 80.6g of 2-amino-1-(4-isopropoxy-2-methylphenyl)-2-methylpropane-1-one as a white powder with a purity of 98.7% and a yield of 99%.

Claims

1. A method for preparing 2-amino-1-(4-isopropoxy-2-methylphenyl)-2-methylpropane-1-one, characterized in that: The steps include: 1) Etherification reaction: dissolving the compound represented by formula (I) and 2-bromopropane in an organic solvent A under stirring, and carrying out a heat-insulating reaction under the catalysis of a base. After the etherification reaction is completed by TLC monitoring, the reaction solution is post-treated to obtain a compound represented by formula (II); 2) Bromination reaction: the compound represented by formula (II) reacts with N-bromosuccinimide in an organic solvent B. After the reaction is completed by TLC monitoring, the reaction solution is post-treated to obtain the compound represented by formula (III); 3) Grignard reaction: the compound represented by formula (III) reacts with magnesium in an organic solvent C at 50° C. for 3-6 hours to obtain a compound represented by formula (IV); under stirring, the compound represented by formula (V) is dissolved in an organic solvent C, and the compound represented by formula (IV) is added. After the reaction is completed by TLC monitoring, the reaction solution is treated to obtain a compound represented by formula (VI); 4) Acid hydrolysis reaction: dissolving the compound represented by formula (VI) in dichloromethane under stirring, adding an acidic species dropwise at 0-25° C., and after the reaction is completed by TLC monitoring, the reaction solution is treated to obtain the compound represented by formula (VII); The reaction process is as follows: Wherein the substituent R in the compound represented by formula (V) is methoxy, ethoxy, phenoxy, benzyloxy or methoxy(methyl)amino.

2. The method for preparing 2-amino-1-(4-isopropoxy-2-methylphenyl)-2-methylpropane-1-one according to claim 1, characterized in that: The organic solvent A in step 1) is N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide or 1,4-dioxane, preferably N-methylpyrrolidone.

3. The method for preparing 2-amino-1-(4-isopropoxy-2-methylphenyl)-2-methylpropane-1-one according to claim 1, characterized in that: The reaction temperature of the heat preservation reaction in step 1) is 80-120°C.

4. The method for preparing 2-amino-1-(4-isopropoxy-2-methylphenyl)-2-methylpropane-1-one according to claim 1, characterized in that: The organic solvent B in step 2) is acetonitrile, dichloromethane or carbon tetrachloride, preferably acetonitrile.

5. The method for preparing 2-amino-1-(4-isopropoxy-2-methylphenyl)-2-methylpropane-1-one according to claim 1, characterized in that: The reaction temperature in step 2) is 10-30°C.

6. The method for preparing 2-amino-1-(4-isopropoxy-2-methylphenyl)-2-methylpropane-1-one according to claim 1, characterized in that: The organic solvent C in step 3) is a mixture of one or more of tetrahydrofuran, ether, and toluene, preferably tetrahydrofuran.

7. A method for preparing 2-amino-1-(4-isopropoxy-2-methylphenyl)-2-methylpropane-1-one as claimed in claim 6, characterized in that: In step 3), the compound represented by formula (V) is dissolved in an organic solvent C, and the reaction temperature is -78 to -50°C when the compound represented by formula (IV) is added.

8. The method for preparing 2-amino-1-(4-isopropoxy-2-methylphenyl)-2-methylpropane-1-one according to claim 7, characterized in that: In step 3), the molar ratio of the compound represented by formula (V) to the compound represented by formula (IV) is 1:1.0 to 1:3.

0.

9. The method for preparing 2-amino-1-(4-isopropoxy-2-methylphenyl)-2-methylpropane-1-one according to claim 1, characterized in that: The acidic species in step 4) is trifluoroacetic acid, acetic acid or hydrochloric acid, preferably trifluoroacetic acid.

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