KR830000995B1 - Method for preparing arylacetic acid ester - Google Patents

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Description

Method for preparing arylacetic acid ester

The present invention relates to a process for preparing esters of arylacetic acid using alpha-halo-alkylarylketones as starting materials. In particular, the present invention relates to a process for preparing esters of lower alcohols of arylacetic acid, even if substituted on a methylene group, by rearranging alpha-halo-alkylarylketones as at least one Ag compound in a lower alcohol and acid medium. It is about.

From the alkyl esters thus prepared, it is desired to obtain the free acid of each alkyl ester by conventional means, such as shifting of the alkali salts prepared by hydrolysis or reaction with alkali, if desired. It is possible.

The products obtained as described above have a considerable number of applications in various industries. In fact, these products can generally be used, for example, as intermediate compounds of industrial products in the field of organic chemistry and in particular in the manufacture of so-called fine chemicals, which are used in the manufacture of perfumes, phytopharmaceutical products (phenyl acetic acid) It has a wide range of applications in pharmaceutical products, which is due to the presence in the "alpha" position of the aryl group for the carboxyester or carboxyl group, which is of most interest to obtain the compounds according to the invention. Increase the likelihood of a reaction.

In particular, according to the invention, it is possible to obtain 2- (6'-methoxy-2'-naphthyl) -alphamethyl acetic acid as alkyl esters and their accompanying free acids, which are intended to be described simply and accurately. This will be referred to hereinafter as 2- (6'-methoxy-2'-naphthyl) -propionic acid, which is in the form of (+) the most in the pharmaceutical field such as anti-inflammatory, analgesic and anti-inflammatory anti-itch agents. It is well applied. These applications are not only described extensively in the literature, but information on the manufacture of related pharmaceutical products such as solutions, suspensions, tablets, capsules, etc., is hereby incorporated by reference (see eg, British Patents 1,211,134).

Thus, the present invention starts with 1- (6'-methoxy-2'-naphthyl) -2-chloro-1-propanone, which is itself a new intermediate compound, as 2- (6'-methoxy) as the final pharmaceutical product. It is an object of the present invention to provide an improved and economical method for preparing -2'-naphthyl) -propionic acid (+), which extends the object of the present invention.

The ester of arylacetic acid obtainable according to the present invention is shown as a compound of the following general structural formula (I).

Wherein Ar is an aryl group or substituted aryl group having 6-30 carbon atoms and R is hydrogen or an alkyl group or substituted alkyl group having 10 carbon atoms and R 'is a monovalent- having up to 10 carbon atoms Or polyvalent alkyl or cycloalkyl alcohol groups.

In conclusion, several methods of preparing arylacetic acid have been proposed. For example, it can be prepared from benzyl halides by substitution by alkaline cyanation and continuous hydrolysis of cyano groups. In fact, 2- (4'-isobutylphenyl) -propionic acid as a pharmaceutical product known as "Ibuprofen" can be prepared by reacting NaCN with the corresponding benzylchloride and subsequently methylation and hydrolysis (US Pat. No. 3,385,886). ).

In any case, the problem with the manufacturing process is that these methods are unlikely to be applied on an actual industrial scale, because of the many and complex production steps required, and that the starting materials used are precise and practically always yielding interesting yields. Because it is not.

On the other hand, various reactions have been described, and it is known that arylacetic acid is obtained by a rearrangement mechanism.

For example, the Willgerodt reaction is known and is the reaction in which an alkylarylketone is converted to the amide or ammonium of the corresponding omega-allyl-alkanoic acid by reaction with ammonium polysulfide. In fact, the rearrangement of aryl groups always occurs on the carbon atom farthest from the carbonyl group and does not occur on the carbon atom in the alpha position relative to the carbonyl group as in the process of the present invention. Furthermore, the yield is not sufficient and the starting compound is alkylarylketone instead of the halotone of the present invention.

Another rearrangement starting with acyl halides results in arylacetic acid by reaction with diazomethane and subsequent hydrolysis in the presence of Ag ₂ O.

The reaction therefore consists of the use of diazo-methane and the formation of diazo-kenone, which are explosive compounds that are not suitable for practical industrial processes. Moreover, this reaction is irregular and results in inconsistent yield.

Finally, rearrangement of alkylaryl ketones to methyl esters of arylacetic acid by thallium salts has been described, but the method is also difficult to apply in this case because of the high toxicity of the thallium salts used.

In general, the above text does not apply to those skilled in the art in a well-defined process of suitable industrial properties suitable for preparing arylacetic acid esters.

Finally, the mechanism of the dehalogenation of 1-benzoyl-1-bromo-cyclohexane with AgSbF ₆ in alcohol is described, what leads to ethylene ketone and some of the transition ester 1-phenyl-1-carboxyalkyl-cyclo The addition to hexane is described. It is a study on the dehalogenation of certain tertiary aryl alpha-halo-ketones, whereas extensively in the literature indicates that no rearrangement reactions occur by silver ion catalysts in alcohols in the presence of primary or secondary alpha-haloketones. This reaction is specifically directed by the process of the present invention.

It has been described to obtain 2-methyl-2-phenylpropionic acid by rearrangement of alpha-bromoisobutyro phenone with AgClO ₄ with or without perchloric acid. Research on this focuses on the mechanism of the process, where rearrangements do not occur with the primary and secondary alpha-halo-ketones, regardless of the presence of perchlorate, but only with the tested tertiary alpha-halo-ketones. It is clearly explained.

With respect to the general prior art, the present invention surprisingly overcomes the bias present in such a technique. Indeed, according to the prior art, arylesters or acids cannot be prepared in the presence of R group of formula (I) other than hydrogen, and it is not possible to start with primary and secondary halo-ketones, but according to the process of the present invention the unexpected The opposite reaction occurs.

It is therefore an object of the present invention, in one step, to provide a simple and economical preparation of the arylacetic ester of formula (I) by rearrangement of the alpha-halo-ketone of formula (II) as defined below, without the drawbacks of the prior art. To provide a way.

In particular, the present invention relates to the preparation of 2 '-(6'-methoxy-2'-naphthyl) -propionic acid as a useful pharmaceutical product.

These objects are achieved by a process for preparing an arylacetic ester having structure (I) according to the present invention, which process comprises a compound of formula wherein the alpha-halo-alkyl arylketone of formula (II) is Has a well-known meaning, and is characterized in that it reacts with a substantially stoichiometric amount of at least one Ag compound in an alcohol medium having the structural formula (I), and the reaction temperature ranges from 0 ° C. to the boiling point of the reaction mixture. The reaction takes place at substantially atmospheric pressure.

Where Ar and R are as described above and X is chlorine, bromine, iodine. Corresponding acids from esters can be prepared by simple conventional techniques such as basic hydrolysis and the like. The process can be represented by the following structural formula.

Where Y is the anion of silver salt and acid will be better defined later, while other symbols have already defined meanings.

More clearly the process is the reaction of Ag salts with aryl alpha-halo-ketone (II) in alcohol media R'OH in the presence of acid at room temperature.

In this way, for example, it is possible to obtain the following products, which are of particular interest in the pharmaceutical art.

The acidity of the reaction medium used from the beginning of reaction (1) is sufficient for the selective formation of most reactive alpha-halo-ketones (II) to arylacetic ester (I). Nevertheless, in the presence of particular aryl alpha-halo-ketone (II) or alcohol R'OH, it is generally preferred to add an acid to the reaction medium in order to improve the yield.

In this way the formation of by-products such as alpha-keroether is reduced to a negligible extent.

In fact, reaction (1) is carried out according to the parameters described below, starting with the aryl alpha-halo-ketone of formula (II) and the alpha position relative to the carbonyl group of alkyl aryl alpha-halo-ketone (II). Rearrangement of the aryl groups on the primary or secondary carbon atoms of gives selectively and unexpectedly the arylacetic esters of formula (I), which are described and disclosed by the prior art as long as they are arranged independently of the presence of other possible free positions. The opposite is true.

Aryl alpha-halo-ketone of formula (II) is a compound per se known and commercially available and can also be prepared by well-known conventional techniques.

Ketones, for example, are prepared by reacting aryl with the desired acyl chloride in nitrobenzene and are also substituted in the presence of an acid catalyst in the form of Lewis acids (AlCl ₃ , SnCl _4, etc.). From this alkyl allyl ketone the alpha-halo = derivatives of formula (II) are obtained by conventional halogenation in solvent (CCl ₄ ).

The preparation of 2-16'-methoxy-2'-naphthyl) -propionic acid (+) represents a typical synthesis starting from 2-methoxy-naphthalene according to the process of the present invention and is described hereinafter.

In reactions (2) and (3), X has the meaning described above.

In Scheme (1), 1- (6'-methoxy-2'-naphthyl) -propane is reacted with 2-methine according to the conventional method by reaction with nitrobenzene or methylene chloride and propionyl chloride in the presence of AlCl _3. It is prepared from methoxy naphthalene.

1- (6'-methoxy-2'-naphthyl) -2-halo-1-propanone in Scheme (2) is obtained from the compound formed in Scheme (1) by conventional halogenation. For example when X = Br, the halogenation reaction is carried out with bromine or other bromine donors in organic solvents such as tetrahydrofuran, methanol.

The halogenation reaction when X = Cl is carried out with a mixture of LiCl / Cu / Cl ₂ in an organic solvent (dimethylformamide, ethyl acetate) in the temperature range of about 50 ° -90 ° C.

The chlorine derivative of the following structural formula (III),

1- (6'-methoxy-2'-naphthyl) -2-chloro-1-propanone is already a new compound by itself and its preparation is mentioned in Example 17 for the purpose of the present invention.

Scheme (3) represents the reaction carried out according to the invention.

Schemes (4) and (5) are respectively prepared by racemic hydrolysis (NaOH) to produce racemic acid (Scheme 4) and dissolving it with cicononidine (Scheme 5) to the desired 2- (6'-methoxy-2 ' -Naphthyl) -propionic acid (+) is prepared and the reaction method is conventional.

4'-methoxy-2-bromoacetophenone, alpha-bromoacetokenone, 1- (2'-naphthyl) -2-bromoethanone, 1- (2'-naphthyl) -2-bromo Tanone, 1- (1'-methoxy-2-naphthyl) -2-bromo-1-propane, 1- (6'-methoxy-2'-naphthyl) -2-chloro-1-prop Panone, 1- (4'-methoxyphenyl) -2-bromo-1-butanone, 1- (4'-phenylphenyl) -2-bromo-1-butanone, 1-('3-meth Methoxyphenyl) -2-bromo-1-propanone, and the like have proven to be efficient alpha-halo-ketones.

The reaction proceeds in alcohol medium.

The alcohol is selected from alkyl or cycloalkyl alcohols or their precursors having up to 10 carbon atoms.

The term "precursor" refers to a compound which, whenever used herein, produces a desired alcohol R'OH under reaction conditions and without interfering with such reactions.

Methyl and ethyl alcohol have proven to be efficient R'OH alcohols. Efficient precursors include alkyl orthoformate acetone dimethylacetal, BF ₃ · 2CH ₃ OH complex salts, and the last compound also has the function of an acid.

BF ₃ · 2CH ₃ OH is a readily available compound and can be obtained from BF ₃ and methanol in any case. Ag salts of organic or inorganic anions and / or mixtures thereof and Ag oxides are colored.

Valid results were obtained by using at least one Ag salt selected from Silver Acetate, AgSbF ₆ (Silver Hexafluoroantimonate), Silver Nitrate, AgBF ₄ (Silver Tetrafluorobocarbonate), AgClO ₄ (Silver Peroxate), AgCF ₃ SO ₃ (Silver Trifluoromethanesulfonate) , Silver carbonate, silver sulfate or oxide.

The acid to be adopted is generally preferably selected from Lewis acids, BF ₃ (boron trifluoride), CF ₃ SO ₃ H (triflu oromethanesulfonic acid), HBF ₄ (fluoroboronic acid), CH ₃ SO ₃ H ( Methanesulfonic acid), H ₂ SO ₄ , complex salt BF ₃ · Et ₂ O (ethylboroethertrifluoride), complex salt BF ₃ · 2CH ₃ COOH, HBF ₄ · Et ₂ O (etherified fluorobotanic acid) and free Below are complex salts BF ₃ .2CH ₃ OH, which act as an acid under reaction conditions and as a source of alcohol CH ₃ OH.

It is generally possible to employ acids in which the warm salt of the acid is dissolved at least in part in the reaction medium.

The reaction is carried out in the presence of excess alcohol R'OH or precursors thereof, indicating that the reaction medium acts as a reactant.

However, if desired in the process, it is also possible to use a substantially inert solvent such as, for example, CH ₂ Cl ₂ , dichlorobenzene, acetonitrile and the like.

The reaction is carried out in a conventional inert gas such as N ₂ argon and preferably free of light. In such cases the concentration can vary over a wide range, which is not critical to the reaction.

The quantitative ratio between the starting aryl alpha-halo-ketone (II) and Ag salts is substantially maintained according to the coefficient of reaction and the effective value is between about 0.2-2 moles for one mole of alpha-halo-ketone (II). It consists of salts. The reacted silver at the end of the reaction is recovered as AgX halide and recycled and recycled according to conventional methods, while the portion of unreacted Ag salt is recovered by acidification (HCL) reaction.

Alcohol R'OH and its initiator are employed in a molar ratio in the range of about 1-200 moles per mole of alpha-halo-ketone (II).

Finally, acid is used as the molar ratio of alpha-halo-ketone (II) in the range of about 0.05-200 moles to 1 mole halo-ketone.

The temperature ranges from 0 ° C. to the boiling point of the mixture, preferably at room temperature.

The reaction time is from 5 minutes to 24 hours, which is usually enough time to complete the reaction depending on the parameters selected.

The process proceeds in the following way.

Alcohol, Ag salts and acids are introduced into a temperature controlled reactor equipped with a stirrer and reactant filling system. Aryl alpha-halo-ketone (II) is then added to the mixture in the desired ratio. The reaction proceeds substantially at room temperature until completion.

After filtration the mixture is diluted with H ₂ O and extracted as water and this extract is washed and dried. The acid is obtained by basic hydrolysis (NaOH) of the ester.

In particular, according to the present invention, 2- (6'-methoxy-2'-naphthyl) -propionic acid (+) is seen as a conventional separation method by the same method as the treatment with synconidine and dihydrocinconidine. Obtained from racemic acid prepared according to the invention.

The process was found to be particularly advantageous due to the mild reaction conditions and the high selectivity of the product obtained. Other advantages will be apparent to those skilled in the art by describing the following examples, which are presented for purposes of illustration only.

Examples 2 and 19 are comparative tests conducted without using an acid. As is clear, the acid yield is much lower, more ether side products are produced and the reaction time is longer.

Example 1

Silver trifluoromethane-sulfonate (3 g, 11.6 m, equivalent to mole) and trifluoromethane-sulfonic acid (6 g, 40 m, equivalent to mole) were added to 10 mM methanol in nitrogen gas. 4'-methoxy-2-bromoacetophenone (2.3 g, 10 m, corresponding to mole) was added to the obtained suspension. The mixture was blocked by light and magnetically stirred at 15 ° C. for 2 hours in the presence of nitrogen gas.

The reaction mixture was then filtered and diluted with water. It was extracted with ethyl ether and the ether extract was washed with water, dried over anhydrous sodium sulfate and then evaporated.

By basic hydrolysis with 50% aqueous sodium in methanol, 4'-methoxy-phenylacetic acid (1.2 g) was obtained from the reaction product in a yield of 75% calculated for the starting ketone.

Example 2 (Comparative Test)

The reaction was carried out as in Example 1 and the reaction was carried out without using an acid. By basic hydrolysis of the reaction product it was possible to obtain 4'-methoxy-phenylacetic acid (0.45 g) with a 27% yield calculated as in Example 1.

Example 3

Of 4-fluoro-2-bromoacetophenone (230 mg, 1 m, equivalent to mde) in trifluoromethane-sulfonate (308 mg, 1.2 m, equivalent to mole) dissolved in trimethyl-orthoformate (2 mι) Added to solution. The mixture was shielded from light and stirred magnetically at 15 ° C. under nitrogen gas for 4 hours. The reaction mixture was treated as described in Example 1. Gas chromatograph analysis of the reaction product revealed that 37% of the charged product was converted to methyl 4'-methoxy-phenylacetic acid salt.

Example 4

Alpha-bromoacetophenone (1 g, 5 m, equivalent to mole) was dissolved in 10 mM trimethyl formate under nitrogen gas. Trifluoromethane-sulfonic acid (0.85 g, 5 m, corresponding to mole) and trifluoromethane-sulfonic acid salt (1.5 g, 5.8 m, corresponding to mole) were added to the solution. The mixture was then shielded from light and magnetically stirred for 24 hours at 15 ° C. under nitrogen gas. The reaction mixture was treated as described in Example 1. In a yield of 20% calculated as in Example 1, phenylacetic acid (0.14 g) was obtained by basic hydrolysis of the reaction product.

Example 5

Alpha-bromoacetophenone (1 g, 5 m, corresponding to mole) was dissolved in 10 mM trimethylortho formate under nitrogen gas. Silver tetrafluoroborate (1.2 g, 5.8 m, corresponds to mole) and BF ₃ .2CH ₃ OH (0.66 g, 5 m, corresponds to mole) were added to the solution. The mixture was shielded from light and stirred magnetically at 50 ° C. for 1 hour 30 minutes under nitrogen gas. The reaction mixture was treated as described in Example 1. By basic hydrolysis of the reaction product phenylacetic acid (0.28 g) was obtained with a yield of 42% calculated as in Example 1.

Example 6

1- (2'-naphthyl) -2-bromoethanone (1.25 g, 5 m, corresponding to mole) was dissolved in 10 mM trimethylorthoformate under nitrogen gas. Silver tetrafluoroborate (1.2 g, 5.8 m, corresponds to mole) and BF ₃ · 2CH ₃ OH (0.66 g, 5 m, corresponds to mole) were added to the solution. The mixture was then shielded from light and magnetically stirred for 1 hour and 15 minutes at 50 ° C. under nitrogen gas. The reaction mixture was treated as described in Example 1. Half-basic hydrolysis of the product gave 2-naphthyl-acetic acid (0.26 g) as a yield of 28% calculated as in Example 1.

Example 7

1- (6'-methoxy-2'-naphthyl) -2-bromo-1-propanone (1.47 g, 5 m, corresponding to mole) was dissolved in 10 mM trimethylorthoformate under nitrogen gas. Silver tetrafluoroborate (2.2 g, 5.8 m, corresponds to mole) and BF ₃ .2CH ₃ OH (0.66 g, 5 m, corresponds to mole) were added to the solution. The mixture was blocked by light and magnetically stirred at 30 ° C. for 3 hours under nitrogen gas.

The reaction mixture was then treated as in Example 1. Basic hydrolysis of the reaction product gave 2- (6'-methoxy-2'-naphthyl) -preionic acid (0.52 g) in a yield of 45% as calculated in Example 1.

Example 8

1- (6'-methoxy-2'-naphthyl) -2-bromo-1-propanone (1.47 g, 5 m, corresponds to mole) and silver tetrafluorobotate (1.2 g, 5.8 m, on mole Is added to 10 mM BF ₃ .2CH ₃ OH under nitrogen gas.

The resulting mixture was shielded under nitrogen pressure at 15 ° C. for 1 hour and stirred magnetically. The reaction mixture was treated as in Example 1. 2- (6'-methoxy-2'-naphthyl) -preionic acid (0.75 g) was obtained in 70% yield as calculated in Example 1 by basic hydrolysis of the reaction product.

Example 9

Silver carbonate (0.83 g, 3 m, equivalent to mole) was dissolved in 10 mι of BF ₃ .2CH ₃ OH and added to 1- (6'-methoxy-2'-naphthyl) -2-bromo- under nitrogen gas. 1-propanone (1.47 g, 5 m, corresponding to mole) was added to the solution.

The mixture thus obtained was blocked with light and stirred magnetically at 15 ° C. for 1 hour 30 minutes under nitrogen gas. The reaction product was treated as described in Example 1. Basic hydrolysis of the reaction product gave 2- (6'-methoxy-2'-naphthyl) -preionic acid (0.82 g) as 75% yield as calculated in Example 1. The racemic 2- (6'-methoxy-2'-naphthyl) -preionic acid obtained therefrom was dissolved in a mixture of 15 mM methanol and 3.5 mmol acetone.

Cinconidine (1.07 g) was dissolved in 11 mmol of methanol and 7 mmol of acetone. These two hot solutions were mixed with each other and cooled to room temperature.

The precipitated salt was filtered off and recrystallized from a mixture of methanol and acetone, which was then stirred in a mixture of dilute HCl and benzene to give a free acid. By evaporating the organic layer, 0..2 g (yield = 49% of theory) 2- (6'-methoxy-2'-naphthyl) -preionic acid (+) was obtained as [a] = + 66 °.

Example 10

Silver acetate (0.97 g, 5.8 m, equivalent to mole) was dissolved in 10 m BF ₃ .2CH ₃ OH. 1- (6'-methoxy-2'-naphthyl) -2-bromo-1-propanone (1.47 g, 5 m, corresponding to mole) was added to the solution under nitrogen gas. The resulting mixture was blocked by light and magnetically stirred for 1 hour and 30 minutes at 150 ° C. under nitrogen gas.

The reaction mixture was then treated as described in Example 1. Basic hydrolysis of the reaction product yielded 2- (6'-methoxy-2'-naphthyl) -preionic acid (0.7 g) as a yield of 65% calculated as in Example 1.

Example 11

Silver oxide (0.7 g, 3 m, equivalent to mole) was dissolved in 10 mM BF ₃ .2CH ₃ OH. 1- (6'-methoxy-2'-naphthyl) -bromo-1-propanone (1.47 g, 5 m, corresponding to mole) was added to the solution under nitrogen gas. The mixture thus obtained was blocked with light and magnetically stirred for 15 hours at 15 ° C. under nitrogen gas. The reaction mixture was then treated as calculated in Example 1. Basic hydrolysis of the reaction product gave 2- (6'-methoxy-2'-naphthyl) -preionic acid (0.7 g) as a yield of 65% calculated as in Example 1.

Example 12

The reaction was carried out as described in Example 9 but with a smaller amount of BF ₃ .2CH ₃ OH (3.3mι). Basic hydrolysis of the reaction product gave 2- (6'-methoxy-2'-naphthyl) -preionic acid (0.7 g) as a yield of 65% calculated as in Example 1.

Example 13

Silver carbonate (0.83 g, 3 m, equivalent to mole) was dissolved in 3.3 mι of BF ₃ .2CH ₃ OH, where 1- (6'-methoxy-2'-naphthyl) -2-chloro-1- Propanone (1.245 g, 5 m, corresponding to mole) was added to the solution under nitrogen gas. The mixture thus obtained was blocked with light and magnetically stirred for 8 hours at 40 ° C. under nitrogen gas. The reaction mixture was treated as described in Example 1. Basic hydrolysis of the reaction product yielded 2- (5'-methoxy-2'-naphthyl) -priionic acid (0.61 g) as a yield of 55% calculated as in Example 1.

Example 14

The reaction was carried out as in Example 1, but the reaction was carried out in ethanol (10mι) instead of methanone. Basic hydrolysis of the reaction product gave 4'-methoxy-phenylacetic acid (0.69 g) as 42% yield calculated as in Example 1.

Example 15

Silver carbonate (0.83 g, 3 m, equivalent to mole) was dissolved in 10 mι of BF ₃ .2CH ₃ OH where 1- (4'-methoxyphenyl) -2-bromo-1-butanone (1.29 g , 5 m, corresponding to mole) was added to the solution under nitrogen gas. The resulting mixture was blocked by light and magnetically stirred for 1 hour and 30 minutes at 15 ° C. under nitrogen gas. The mixture was then treated as described in Example 1. By basic hydrolysis of the reaction product, 2- (4'-methoxyphenyl) -butanoic acid (0.5 g) was obtained with a yield of 52% calculated as in Example 1.

Example 16

1- (1'-naphthyl) -2-bromoacetone (1.25 g, 5 m, corresponding to mole) was dissolved in 10 mM trimethyl-orthoformate under nitrogen gas. Silver tetrafluoroborate (1.2 g, 5.8 m, corresponds to mole) and BF ₃ .2CH ₃ OH (0.66 g, 5 m, corresponds to mole) were added to the solution. The mixture was then blocked by light and magnetically stirred for 1 hour and 30 minutes at 50 ° C. under nitrogen gas. The reaction mixture was then treated as described in Example 1.

Basic hydrolysis of the reaction product gave 1-naphthylacetic acid (0.23 g) in a yield of 25% calculated as in Example 1.

Example 17

Silver carbonate (0.83 g, 3 m, equivalent to mole) was dissolved in 10 mι of BF ₃ · 2CH ₃ OH, where 1- (3'-phenoxyphenyl) -2-bromo-1-propanone (1.53 g , 5 m, corresponding to mole) was added to the solution under nitrogen gas. The mixture thus obtained was blocked with light and magnetically stirred at 15 ° C. for 2 hours under nitrogen gas. It was possible to obtain 2- (3'-phenoxyphenyl) -propionic acid by basic hydrolysis of the reaction product. The product was confirmed by comparison with known samples.

Example 18

Silver carbonate (0.5 g, 18 m, equivalent to mole) was dissolved in ₃₀ mι of BF ₃ · 2CH ₃ OH where 1- (4'-phenylphenyl) -2-bromo-1-butanone (9.1 g, 30 m , mole) was added to the solution under nitrogen gas. The mixture was blocked by light and magnetically stirred at 15 ° C. for 20 hours under nitrogen gas. The reaction mixture was then treated as described in Example 1. By basic hydrolysis of the reaction product 2- (4'-phenylphenyl) -butanoic acid (2.9 g) was obtained with a yield of 41% calculated as in Example 1.

Example 19 (Comparative Test)

1- (6'-methoxy-2'-naphthyl) -2-bromo-1-propanone (1.47 g, 5 m, equivalent to mole) and silver tetrafluoro borate (1.2 g, 5.8 m, in mole Was added to 10 mM methanol under nitrogen gas. The mixture thus obtained was blocked with light and magnetically stirred at 15 ° C. for 24 hours under nitrogen gas. The reaction mixture was then treated as described in Example 1. The reaction product was 1- (6'-methoxy-2'-naphthyl) -2-methoxy-1-propanone (0.66 g, calculated as in Example 1 = 55%, melting point = 58 °- 60 ° C.) and 2- (6′-methoxy-2′-naphthyl) -pripionic acid (0.195 g, calculated yield as in Example 1 = 17%).

Example 20

Synthesis of 1- (6'-methoxy-2'-naphthyl) -2-chloro-1-propanone (III) Dihydrated racemic chloride (12.28 g, 0.072 m, equivalent to mole) and lithium chloride (1.53 g, 0.036m, mole) and a 20-neck N, N-dimethylformamide 50mι three-necked flask was installed magnetic stirrer, thermometer and bubble cooler. After the mixture was heated to 80 ° C., 1- (6′-methoxy-2′-naphthyl) -1-propanone (6.45 g, 0.03 m, corresponds to mole) was added.

Stirring was performed at 80 ° -90 ° C. for 2 hours. The reaction mixture was then placed on ice and acidified with hydrochloric acid to dissolve copper chloride, which precipitated. Extracted with ether, then ether extract was washed with water, dried over anhydrous sodium sulfate and evaporated. 6.63 g of product (III) (yield = 89%) was obtained by crystallization in ethanol (melting point = 77 ° -80 ° C). Elemental analysis, NMR, IR, and mass spectrometry confirm the structure of (III).

Claims (1)

The alpha-halo-alkylarylketone of the formula A process for preparing the aryl acetate ester of the following formula (I) characterized by reacting with at least one Ag compound under:

Wherein Ar is an aryl group or substituted aryl group having 6-30 carbon atoms and R is a hydrogen atom or an alkyl group or substituted alkyl group having 1-10 carbon atoms and R 'has up to 10 carbon atoms Residues of mono- or polyhydric alkyl or cyclo alkyl alcohols.