JP4189108B2 - Method for producing amino acid ester hydrochloride - Google Patents

Description

何れの実施例においても、反応副成物の生成量は、比較例１の約１／１０であることが分かる。
【００４９】
【発明の効果】
本発明のアミノ酸エステル塩酸塩の製造方法は、反応系となる液相部に直接塩化水素ガスを吹き込む従来の製造方法に比べて、不純物となる副生物の生成量を大幅に低減することができる。したがって、精製工程を簡略化若しくは省略することが可能である。また、本発明の製造方法では、反応速度や塩化水素の利用率の点では上記従来法と遜色がないばかりでなく、反応中に塩化水素ガス供給ラインに反応液が逆流するといったトラブルが発生することも実質的にない。このため、このようなトラブルに対処する為の装置上の負担、および作業量や安全性の面での人的負担を削減することができる。
【００５０】
このように、高純度のアミノ酸エステル塩酸塩を効率よく、しかも安全且つ簡便に製造することが出来るという点で、本発明の製造方法は工業的に優れたアミノ酸エステル塩酸塩の製造方法であるといえる。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a method for producing an amino acid ester hydrochloride useful as a sweetener or a pharmaceutical intermediate with high purity.
[0002]
[Prior art]
Amino acid ester hydrochloride is a very important compound as an intermediate between sweeteners, HIV protease inhibitors and other physiologically active substances.
[0003]
The amino acid ester hydrochloride has heretofore been produced by blowing a stoichiometric amount of hydrogen chloride gas into a suspension of an amino acid suspended in alcohol (Japanese Patent Laid-Open No. 7-101928).
[0004]
[Problems to be solved by the invention]
However, the above-described method has a problem that by-products as impurities are unavoidably generated although the amount is relatively small, 0.1 to 0.3 mol%. That is, depending on the use of the amino acid ester hydrochloride, it is desired that the content of impurities other than the raw material is 0.1 mol% or less, and the amino acid ester hydrochloride obtained by the conventional method is used for such use. For this purpose, purification by a recrystallization method, a reprecipitation method, a column chromatography method or the like had to be performed. Incorporation of such a purification step not only complicates the operation and increases the time required for production, but also causes a problem that the isolation yield of the target product is reduced. There is a desire for a production method with less.
[0005]
Further, in the above method, there is a problem that when the pressure or the blowing speed when hydrogen chloride gas is blown is lowered, the reaction solution flows back in a large amount into the pipe for supplying hydrogen chloride gas. In order to avoid the occurrence of such problems, it has been necessary to carry out the production while paying close attention, for example, by installing a backflow prevention valve, a backflow prevention trap, etc., and constantly monitoring the reaction state.
[0006]
The present invention is a method for producing an amino acid ester hydrochloride, which does not produce a by-product as an impurity, can eliminate a purification step, and has a risk of causing troubles such as reverse flow of hydrogen chloride gas. The aim is to provide no manufacturing method.
[0007]
[Means for Solving the Problems]
In order to solve the above-mentioned problems, the present inventors first studied the identification of impurities and the cause of the generation of the impurities. As a result, the impurity is an N-alkyl amino acid ester hydrochloride substituted with an alkyl group of the alcohol used as a raw material, and the impurity is generated in the region near the tip of the hydrogen chloride gas blowing tube. The reaction temperature is locally high and the hydrogen chloride gas concentration in the region is high, so that hydrogen chloride reacts with alcohol to produce alkyl chloride, which reacts with the starting amino acid. I found out.
[0008]
And then, based on such knowledge, an attempt was made to suppress the occurrence of the above-mentioned local region that becomes a reaction field of side reaction by tightening the stirring conditions, but the desired effect was obtained. There wasn't.
[0009]
Therefore, intensive studies were conducted on other methods that do not cause the local reaction as described above. As a result, hydrogen chloride gas was blown into the gas phase part of the reactor without being bound by general common sense in gas-liquid reactions, and if the liquid phase part was sufficiently stirred, the reaction rate was hardly affected. As a result, it was found that side reactions were suppressed and the present invention was completed.
[0010]
That is, the present invention relates to a method for producing an amino acid ester hydrochloride by reacting an amino acid and an alcohol in the presence of hydrogen chloride in a liquid phase in the reactor, and hydrogen chloride gas is introduced into the gas phase portion in the reactor. A method for producing an amino acid ester hydrochloride, which is introduced and supplied to a reaction system.
[0011]
In general, a gas-liquid heterogeneous reaction is usually performed by blowing a gas (gas) into the liquid phase as in the conventional method in order to increase the absorption efficiency of the gas into the liquid phase. In the reaction system in the production method of the invention, even if gas is blown into the gas phase portion, the target reaction proceeds without a significant decrease in the reaction rate. In addition, since a region where the temperature and hydrogen chloride concentration are locally high is unlikely to be generated, the production of the by-product is also suppressed. Furthermore, since the tip of the hydrogen chloride supply nozzle does not come into contact with the reaction solution, the reaction solution does not flow backward into the pipe. As a result, amino acid ester hydrochloride can be produced with high purity and safety.
[0012]
DETAILED DESCRIPTION OF THE INVENTION
In the production method of the present invention, an amino acid ester hydrochloride is produced by reacting an amino acid with an alcohol in the presence of hydrogen chloride in a liquid phase in the reactor. In this production method, amino acid and hydrogen chloride first react to form amino acid hydrochloride, and then amino acid hydrochloride and alcohol react in the presence of excess hydrogen chloride to form amino acid ester hydrochloride. It is.
[0013]
As the amino acid used in the present invention, a known compound having at least one amino group and a carboxyl group or a group derived from a carboxyl group in the molecule can be used without any limitation. Here, the amino group means a primary or secondary amino group, for example, at least one nitrogen atom such as an alkyl group or a mono-substituted amino group substituted with a hydrocarbon group such as an aralkyl group or a pyrrolidyl group. It means a group to which a hydrogen atom is bonded.
[0014]
In addition, a group derived from a carboxyl group is derived from a carboxyl group (—COOH group) in which a proton is substituted with another cation to form a salt, an esterified alkoxycarbonyl group or the like. Means a group capable of esterification or transesterification.
[0015]
Specific examples of amino acids that can be suitably used in the present invention include glycine, phenylglycine, N-methylglycine, N-ethylglycine, N-benzylglycine, hydroxyphenylglycine, alanine, N-methylalanine, N- Ethylalanine, N-benzylalanine, β-alanine, N-methyl-β-alanine, N-ethyl-β-alanine, N-benzyl-β-alanine, serine, homoserine, isoserine, O-benzylserine, cysteine, S Acetamide cysteine, cystine, homocystin, threonine, O-benzyl threonine, methionine, homomethionine, valine, N-methyl valine, N-ethyl valine, N-benzyl valine, norvaline, N-methyl norvaline, N-ethyl norvaline, N -Benzylnorvaline, Icine, N-methylleucine, N-ethylleucine, N-benzylleucine, norleucine, N-methylnorleucine, N-ethylnorleucine, N-benzylnorleucine, isoleucine, N-methylisoleucine, N-ethylisoleucine, N -Benzylisoleucine, phenylalanine, N-methylphenylalanine, N-ethylphenylalanine, N-benzylphenylalanine, hydroxyphenylalanine, tyrosine, O-benzyltyrosine, tyrosine, O-benzyltyrosine, proline, hydroxyproline, O-benzylhydroxyproline, tryptophan , Aspartic acid, asparagine, glutamic acid, homoglutamic acid, glutamine, arginine, N-tosylarginine, N-benzylarginine, ornithine, human Examples include stidine, α-aminobutyric acid, β-aminobutyric acid, γ-aminobutyric acid, α-aminoisobutyric acid, lysine, and the like.
[0016]
Each of these amino acids may have a substituent and may be protected. Furthermore, it may be an optically active substance, a racemic mixture containing optical isomers, or a mixture of different amino acids.
[0017]
In the present invention, the alcohol used for the reaction with an amino acid is not particularly limited, but an alcohol having 1 to 10 carbon atoms is preferable from the viewpoint of reactivity. Specific examples of alcohols that can be suitably used in the present invention include methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutyl alcohol, t-butyl alcohol, n-amyl alcohol, isoamyl alcohol, Examples thereof include t-amyl alcohol, n-hexyl alcohol, cyclohexyl alcohol, allyl alcohol, and benzyl alcohol.
[0018]
Among these alcohols, it is preferable to use methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, n-hexyl alcohol, cyclohexyl alcohol, benzyl alcohol or the like that can be easily converted into an ester. These alcohols may be used in combination of two or more.
[0019]
The amount of alcohol used in the present invention is not limited as long as it is 1 equivalent or more with respect to the carboxyl group of the amino acid because the esterification reaction or transesterification reaction is an equivalent reaction of amino acid and alcohol. In order to have the role of, too much is used. However, if the amount is too large, the yield per batch is lowered and it is not economical, so the concentration of amino acids in the alcohol is usually 0.1 to 90% by weight, preferably 1 to 80% by weight. Is preferred.
[0020]
In the production method of the present invention, it is preferable to use a solvent because the reaction is carried out in the liquid phase. As the solvent, excess alcohol may be used as a solvent as described above, but other solvents may be mixed and used. As the other solvent, it is preferable to use an organic solvent that does not react with the reaction raw material amino acid or alcohol.
[0021]
Specific examples of the organic solvent that can be suitably used in the present invention include halogenated aliphatic hydrocarbons such as dichloromethane, chloroform, 1,2-dichloroethane, carbon tetrachloride, and trichloroethylene, ethyl acetate, n-propyl acetate, acetic acid. Esters such as isopropyl, n-butyl acetate, isobutyl acetate, t-butyl acetate, ethyl formate, n-propyl formate, isobutyl formate, ethyl propionate, n-butyl propionate, t-butyl propionate, benzene, toluene, Aromatic hydrocarbons such as o-xylene, m-xylene and p-xylene, halogenated aromatic hydrocarbons such as chlorobenzene, o-dichlorobenzene, m-dichlorobenzene and p-dichlorobenzene, diethyl ether, tetrahydrofuran, 1, 4-dioxane, butyl ethyl ether, di Ethers such as sopropyl ether, ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone, carbonates such as dimethyl carbonate, nitriles such as acetonitrile and propionitrile, n-pentane, n-hexane, n-heptane and trimethyl Examples thereof include aliphatic hydrocarbons such as pentane, cyclic aliphatic hydrocarbons such as cyclohexane, amides such as dimethylformamide and dimethylacetamide, dimethyl sulfoxide, and the like. Among them, halogenated aliphatic hydrocarbons such as dichloromethane, chloroform, 1,2-dichloroethane, ethyl acetate, n-propyl acetate, isopropyl acetate, n-butyl acetate, ethyl formate, n-propyl formate, isobutyl formate, propionic acid Esters such as ethyl, aromatic hydrocarbons such as benzene, toluene and m-xylene, halogenated aromatic hydrocarbons such as chlorobenzene and o-dichlorobenzene, ethers such as diethyl ether, tetrahydrofuran and 1,4-dioxane, Ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone, carbonates such as dimethyl carbonate, nitriles such as acetonitrile, aliphatic hydrocarbons such as n-pentane, n-hexane and n-heptane, and cycloaliphatics such as cyclohexane Hydrocarbons, di Chill formamide, amides such as dimethylacetamide, dimethyl sulfoxide and the like. Two or more of these organic solvents may be used in combination.
[0022]
The amount of these organic solvents used varies depending on the amount of alcohol used and the type of organic solvent, and cannot be generally stated. However, the concentration of amino acids is usually 0.1 to 90% by weight, preferably 1 to 80% by weight. In general, the total amount of alcohol and organic solvent is determined so as to be%.
[0023]
Since the esterification reaction of amino acids is greatly inhibited by water, the content of water in the alcohol and organic solvent used in this reaction is 1% by weight or less, preferably 0.5% by weight or less based on amino acids. It is preferable to dehydrate it. Alcohol and organic solvent dehydration methods vary widely depending on the type of compound, so they cannot be generally stated. In general, azeotropic dehydration methods, calcium chloride, calcium oxide, calcium sulfate, magnesium sulfate, calcium hydride, sodium, etc. A method using a dehydrating agent such as hydride, sodium or diphosphorus pentoxide is employed.
[0024]
In the production method of the present invention, when the amino acid and alcohol are reacted in the liquid phase in the reactor in the presence of hydrogen chloride, hydrogen chloride gas is introduced into the gas phase portion in the reactor, and the hydrogen chloride is reacted. Hydrogen gas is supplied to the reaction system by contacting the gas with at least one of the components constituting the liquid phase (hereinafter, this contact is also simply referred to as gas-liquid contact).
[0025]
When hydrogen chloride gas is blown directly into the liquid phase portion, it is inevitable that N-alkylamino acid ester hydrochloride, which is a by-product as described above, is produced in an amount of 0.1 mol% or more, and the reaction solution is further chlorinated. There is a risk of backflow through the hydrogen gas inlet pipe.
[0026]
The method of introducing hydrogen chloride gas into the gas phase part in the reactor is not particularly limited, for example, through a gas introduction pipe set at a position where the tip does not touch the liquid layer part in the reactor. It can carry out suitably by introducing from a hydrogen chloride gas cylinder. As the hydrogen chloride gas, any industrially available gas can be used without particular limitation.
[0027]
The method of bringing the hydrogen chloride gas introduced into the gas phase portion in the reactor into gas-liquid contact is not particularly limited, but by stirring the liquid phase portion to be contacted from the viewpoint of good efficiency and required equipment and ease of operation. It is preferable to carry out the process so that the gas phase is involved in the liquid phase part. In this case, the method of stirring the liquid phase portion is not particularly limited, and mechanical stirring using a stirring blade, magnetic stirring using a stirring bar, mill stirring using various shaped mills, vibration due to vibration. A known stirring method such as stirring and liquid feeding stirring by circulation of the reaction solution can be employed without any limitation. The agitation conditions are not particularly limited, but mechanical agitation is most preferable from the viewpoint of the reaction speed and reaction efficiency. The agitation blade is also a paddle type, a receding blade paddle type (Faudler type), a flat plate type (full zone type), Max Blend. A mold, an inclined blade type, a propeller type, a sawtooth type, a turbine type, a curved blade turbine type, a curved turbine type, a single-sided disk turbine type, a blue margin type, a saddle type, a helical ribbon type, or the like may be used. Two or more types of these stirring blades may be used in combination.
[0028]
The number of rotations in the stirring depends on the shape of the stirring blades, and thus cannot be generally defined, but is usually selected appropriately in the range of 2 to 10,000 rpm.
[0029]
The liquid phase part to be brought into gas-liquid contact may be at least one liquid component constituting the liquid phase as a reaction system, and may be a suspension containing an amino acid and an alcohol or a solution used as necessary. It may be an alcohol, a solvent, or a mixture thereof (none of them contains an amino acid). In the former case, hydrogen chloride is supplied to the reaction system simultaneously with the gas-liquid contact. In the latter case, hydrogen chloride is supplied to the reaction system by bringing the liquid phase portion after gas-liquid contact into contact with an amino acid and alcohol (when the solvent is in gas-liquid contact). Here, the reaction system means a system in which amino acids, alcohols, and hydrogen chloride coexist.
[0030]
In the present invention, from the viewpoint that the operation is simple, the structure of the apparatus to be used is simple, and hydrogen chloride gas can be continuously supplied, from a suspension or solution containing an amino acid and an alcohol. It is preferable to make gas-liquid contact with the liquid phase part.
[0031]
The total amount of hydrogen chloride gas introduced is preferably equimolar or more with respect to amino acids from the viewpoint of reaction efficiency. Hydrogen chloride gas may be introduced at a time before the start of the reaction, or intermittently or continuously during the reaction. From the viewpoint of ease of operation, it is preferable to introduce a predetermined amount of hydrogen chloride gas at a time before the reaction.
[0032]
In the case of continuous introduction, the introduction rate may be appropriately determined according to the amino acid to be used, the alcohol, the amount of the solvent to be used if necessary, the reaction temperature, and the reaction pressure. From the viewpoint of effective utilization, it is preferably 0.001 to 1000 mol / (mol amino acid · min) in terms of moles of hydrogen chloride supplied per minute per amino acid.
[0033]
In addition, the hydrogen chloride gas partial pressure at the time of introducing hydrogen chloride gas can be selected from a wide range of pressurization, for example, 0.001 kgf / cm ^{2 to} 100 kgf / cm ^2. From 0.01 kgf / cm ^{2 to} 90 kgf / cm ² , particularly preferably from 0.1 kgf / cm ^{2 to} 80 kgf / cm ² .
[0034]
The reaction conditions of the reaction performed after supplying hydrogen chloride to the reaction system (esterification reaction or transesterification reaction with amino acid and alcohol, and formation of salt with purified ester and hydrochloric acid) are particularly different from conventional reactions. Absent.
[0035]
The reaction pressure ^{is, 0.01kgf / cm 2 ~90kgf / cm} 2, in particular being set in the range of 0.1kgf / cm ² ~80kgf / cm ² is usually. The reaction can be carried out with the atmosphere open, but in that case, since the progress of the reaction may be hindered by moisture in the atmosphere, the reaction may be released to the atmosphere through a desiccant such as calcium chloride. Is preferred. However, from the viewpoint of safety, it is preferable to carry out the reaction in an atmosphere of an inert gas such as nitrogen, argon or helium, or in a sealed condition.
[0036]
In addition, the reaction temperature is not particularly limited as long as it is within the range of the freezing point of the system to the boiling point under the pressure at the time of reaction. If the amount is too high, the esterification reaction rate is significantly reduced.
[0037]
The reaction time varies depending on the reaction temperature and the type of alcohol and amino acid used, but is usually in the range of 1 to 120 hours. The reaction can be carried out either batchwise or continuously.
[0038]
By carrying out the reaction by such a method, the target amino acid ester hydrochloride can be obtained efficiently. The obtained amino acid ester hydrochloride can be separated and used by distilling off the solvent from the reaction solution, or neutralized with an amine or an inorganic base without isolation to obtain an amino acid ester, It can also be used as a raw material for amino group protection reaction, carbon increase reaction, or ester site reduction reaction.
[0039]
The method for separating the amino acid ester hydrochloride from the reaction solution is not particularly limited, and a known separation method can be employed. For example, when the target substance is a liquid or oily substance, it can be isolated as it is or by adding an organic solvent to dissolve it and separating it as a solution of the organic solvent, and then removing the solvent. In addition, when the target product is a crystal, it is crystallized from such a solution by a known method such as recrystallization or reprecipitation, and a filtration method such as natural filtration, pressure filtration or vacuum filtration, decantation, or centrifugation. It can be isolated by solid-liquid separation by a method such as
[0040]
【Example】
EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated, this invention is not restrict | limited to these Examples.
[0041]
Example 1
After replacing the inside of the container with nitrogen in a 2 L glass autoclave equipped with a gas supply pipe, a stirrer, and a thermometer, 165.19 g (1.00 mol) of L-phenylalanine and 248 g (7.74 mol) of methanol were added. Cooled below ℃. Next, 72.92 g (2.00 mol) of hydrogen chloride was supplied through a gas supply pipe so that the secondary pressure of the hydrogen chloride gas cylinder was 1.0 kgf / cm ² and the pressure of the reaction vessel was 0.5 kgf / cm ² . . At this time, the tip (gas outlet) of the gas supply pipe was adjusted to a position where it did not come into contact with the liquid layer when the liquid layer was stirred, and introduced into the gas phase part. At this time, mechanical stirring was used for stirring, a two-blade paddle type stirring blade was used, and the rotation speed was maintained at 200 rpm. After completion of the gas-liquid contact, the liquid temperature was raised to 35 ° C., and the reaction was performed by stirring for 6 hours while maintaining the temperature.
[0042]
After completion of the reaction, the reaction solution was quantified by high performance liquid chromatography (hereinafter abbreviated as HPLC), and the composition thereof was 99.47 mol% of L-phenylalanine methyl ester hydrochloride as a target product, L as a reaction intermediate. It was 0.50 mol% of phenylalanine hydrochloride and 0.03 mol% of N-methyl-L-phenylalanine methyl ester hydrochloride which is a reaction byproduct. Further, no back flow of the reaction solution occurred.
[0043]
Example 2
After replacing the inside of the container with argon in the same 2 L glass autoclave used in Example 1, 165.19 g (1.00 mol) of L-phenylalanine and 248 g (7.74 mol) of methanol were added and cooled to 10 ° C. or lower. did. Next, 72.92 g (2.00 mol) of hydrogen chloride was supplied to the gas phase part so that the secondary pressure of the hydrogen chloride gas cylinder was 1.5 kgf / cm ² and the pressure of the reaction vessel was 1.0 kgf / cm ² . At this time, mechanical stirring was used for stirring, a two-blade paddle type stirring blade was used, and the rotation speed was maintained at 300 rpm.
[0044]
Thereafter, gas-liquid contact and reaction were carried out in the same manner as in Example 1. After completion of the reaction, the reaction solution was quantified by HPLC. As a result, 99.58 mol% of the target L-phenylalanine methyl ester hydrochloride was obtained as a reaction intermediate. It was 0.40 mol% of certain L-phenylalanine hydrochloride and 0.02 mol% of N-methyl-L-phenylalanine methyl ester hydrochloride which is a reaction byproduct. Moreover, the backflow of the reaction liquid was not confirmed.
[0045]
Comparative Example 1
After replacing the inside of the container with nitrogen in a 2 L glass autoclave equipped with a gas introduction tube, a stirrer, and a thermometer, 165.19 g (1.00 mol) of L-phenylalanine and 248 g (7.74 mol) of methanol were added. Cooled below ℃. Next, 72.92 g (2.00 mol) of hydrogen chloride is liquidated through the gas supply pipe so that the secondary pressure of the hydrogen chloride gas cylinder is 1.0 kgf / cm ² and the pressure of the reaction vessel is 0.5 kgf / cm ^2. Feeded to the phase section. The supply of hydrogen chloride gas to the liquid layer was adjusted so that the tip (gas outlet) of the gas supply pipe was near the bottom of the reaction vessel. At this time, mechanical stirring was used for stirring, a two-blade paddle type stirring blade was used, and the rotation speed was maintained at 200 rpm. After completion of the gas-liquid contact, the liquid temperature was raised to 35 ° C., and the reaction was performed by stirring for 6 hours while maintaining the temperature.
[0046]
After completion of the reaction, the reaction solution was quantified by high performance liquid chromatography (hereinafter abbreviated as HPLC), and its composition was 99.23 mol% of L-phenylalanine methyl ester hydrochloride as the target product, L as the reaction intermediate. It was 0.50 mol% of phenylalanine hydrochloride and 0.27 mol% of N-methyl-L-phenylalanine methyl ester hydrochloride which is a reaction byproduct. In addition, a back flow of the reaction solution was observed.
[0047]
Examples 3-12
Similar to Example 1 except that the secondary pressure of the amino acid, alcohol, hydrogen chloride cylinder, the pressure in the reaction vessel, the temperature of the reaction liquid at the time of gas-liquid contact, the reaction temperature, and the reaction time were changed to the conditions shown in Table 1. The composition of the resulting reaction solution was analyzed by HPLC. The results are shown in Table 1. In any case, no back flow of the reaction solution was confirmed.
[0048]
[Table 1]

In any of the examples, it can be seen that the production amount of the reaction by-product is about 1/10 of that of Comparative Example 1.
[0049]
【The invention's effect】
The production method of the amino acid ester hydrochloride of the present invention can greatly reduce the amount of by-products that become impurities, compared to the conventional production method in which hydrogen chloride gas is directly blown into the liquid phase portion that becomes the reaction system. . Therefore, the purification process can be simplified or omitted. In addition, the production method of the present invention is not only inferior to the above conventional method in terms of reaction rate and hydrogen chloride utilization rate, but also causes a problem that the reaction solution flows back to the hydrogen chloride gas supply line during the reaction. There is virtually nothing. For this reason, it is possible to reduce the burden on the apparatus for dealing with such a trouble and the human burden in terms of work amount and safety.
[0050]
As described above, the production method of the present invention is an industrially superior method for producing amino acid ester hydrochlorides in that it can efficiently produce amino acid ester hydrochlorides of high purity efficiently and safely. I can say that.

Claims (1)

In a method for producing an amino acid ester hydrochloride by reacting an amino acid and an alcohol in the presence of hydrogen chloride in a liquid phase in the reactor, hydrogen chloride gas is introduced into the gas phase portion in the reactor and introduced into the reaction system. A process for producing an amino acid ester hydrochloride, characterized in that it is supplied.