JPH021135B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel aminocarboxylic acid derivative and a method for producing the same. More specifically, the present invention relates to a novel aminocarboxylic acid derivative that is expected to be used as a pharmaceutical such as an anti-ulcer agent, and a method for producing the same. According to the present invention, the following formula [] [In the formula, R ¹ represents an acyl group having 1 to 7 carbon atoms, and X ¹ represents an alkylene group having 3 to 6 carbon atoms, 1,4
-Represents a cyclohexylene group or a 1,4-phenylene group, R ² and R ³ together represent an oxo group, X ² represents an alkylene group having 1 to 6 carbon atoms, and R ⁴ represents -COOR ⁵ In the formula, R ⁵ is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms. ] A novel aminocarboxylic acid derivative or a salt thereof is provided. On the other hand, the literature Journal of American Chemical Society (Journal of
American Chemical Society), vol. 81, 1959,
For 4639 to 4643., the following formula 3-(p-Aminoacetylphenyl)propionic hydrochloride represented by is described as an intermediate of chlorambucil having anticancer activity. Also, in Japanese Patent Application Laid-open No. 51-101134, the following formula [In the formula, Q means a substituted or unsubstituted phenyl group or β-naphthyl group, and the substituted phenyl group includes p-halogenophenyl group, o-alkoxy-p
- Represents a formyl phenyl group, bisphenyl group, p-carboxyvinylphenyl group, p-carboxyphenyl group, p-(β-aminocarboxyethyl) phenyl group or p-(carboxy lower alkyl) phenyl group. ] Amino acid esters having anti-ulcer effects shown in the following are described. However, the aminocarboxylic acid derivative provided by the present invention has a structure different from those of these known compounds, is a new compound that has not been described in any literature, and has a different pharmacological action from these known compounds. It is a compound that is expected to be used as a pharmaceutical agent such as an anti-ulcer agent, and is also expected to be used as a precursor of a pharmaceutical agent such as an anti-ulcer agent. The aminocarboxylic acid derivative of the above formula [] is
Based on the definitions of R ² and R ³ , it can be divided into the following compounds. That is, the following formula [ ] - a [In the formula, R ¹ , X ¹ , X ² and R ⁴ are the same as defined above. ] It is an aminocarboxylic acid derivative or a salt thereof represented by: R ¹ is an acyl group having 1 to 7 carbon atoms. Such acyl groups include, for example, formyl, acetyl,
Examples include propionyl, butyryl, valeryl, caproyl, heptanoyl and the like. Among these, R ¹ is particularly preferably an acetyl group. X ¹ is an alkylene group having 3 to 6 carbon atoms, 1,4-
Represents a cyclohexylene group or a 1,4-phenylene group. As an alkylene group having 3 to 6 carbon atoms,
Examples include trimethylene group, tetramethylene group, pentamethylene group, hexamethylene group, and the like. X ² is an alkylene group having 1 to 6 carbon atoms. Examples of the alkylene group having 1 to 6 carbon atoms include methylene, dimethylene, trimethylene, tetramethylene, and pentamethylene. Examples of the alkyl group having 1 to 6 carbon atoms as a substituent include methyl, ethyl, n-propyl, iso-propyl, n
-butyl, iso-butyl, tert-butyl, N-pentyl, n-hexyl, etc. Among these, X ² is preferably a methylene group or a dimethylene group. R ⁴ is a group represented by -COOR ⁵ , and R ⁵ is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms. That is, when R ⁵ is a hydrogen atom, R ⁴ is a carboxyl group, and when R ⁵ is an alkyl group having 1 to 6 carbon atoms,
R ⁴ is an ester group. Examples of the alkyl group having 1 to 6 carbon atoms are the same as those exemplified above for ^X2 . In the above formula [], when X ¹ is a 1,4-cyclohexylene group, it may be in either a chair-shaped or boat-shaped form, and even if the two bonds are in a cis relationship, a trans There may be a relationship between Preferably, it is in a transformer relationship in the form of a chair. When R ⁴ is a carboxyl group (when R ⁵ is a hydrogen atom), the aminocarboxylic acid derivative of the present invention can be a salt at this carboxyl group. Preferred salts for carboxyl groups include salts with alkali metals, 1/2 equivalent of alkaline earth metals, 1/3 equivalent of aluminum, ammonium, and the like. Among these, salts of lithium, sodium, potassium, 1/2 calcium, 1/2 magnesium, and 1/3 aluminum are particularly preferred. Examples of the compound represented by the above formula [] provided by the present invention include the following compounds. (i) Compound (100) 3-[p-(4-N-acetylaminomethylcyclohexylcarbonyl)phenyl] represented by formula []-a
Propionic acid, (102) 3-[p-(4-N-propionylaminomethylcyclohexylcarbonyl)phenyl]propionic acid, (104) 3-[p-(4-N-caproylaminomethylcyclohexylcarbonyl)phenyl]propion Acid, (108) 2-[p-(4-N-acetylaminomethylcyclohexylcarbonyl)phenyl]
Acetic acid, (110) 4-[p-(4-N-acetylaminomethylcyclohexylcarbonyl)phenyl]
Butyric acid, (112) 3-[p-(4-N-acetylaminomethylcyclohexylcarbonyl)phenyl]
Methyl propionate, (114) 3-[p-(4-N-propionylaminomethylcyclohexylcarbonyl)phenyl]ethyl propionate, (116) 3-[p-(4-N-caproylaminomethylcyclohexylcarbonyl)phenyl ]Butyl propionate, (118) 2-[p-(4-N-acetylaminomethylcyclohexylcarbonyl)phenyl]
Methyl acetate, (120) 4-[p-(4-N-acetylaminomethylcyclohexylcarbonyl)phenyl]
Methyl butyrate, (134) 3-[p-(4-N-acetylaminomethylbenzoyl)phenyl]propionic acid, (136) 3-[p-(4-N-acetylaminomethylbenzoyl)phenyl]methyl propionate, (138) 3-[p-4-N-acetylaminomethylbenzoyl)phenyl)butyl propionate, (140) 2-[p-(4-N-acetylaminomethylbenzoyl)phenyl]acetic acid, (142) 2- [p-(4-N-acetylaminomethylbenzoyl)phenyl]methyl acetate, (144) 4-[p-(4-N-acetylaminomethylbenzoyl)phenyl]butyric acid, (146) 4-[p-(4 -N-caproylaminomethylbenzoyl)phenyl]methyl butyrate, (156) 3-[p-(δ-N-acetylaminovaleryl)phenyl]propionic acid, (158) 3-[p-(ε-N- acetylaminocaproyl)phenyl]propionic acid, (159) 3-[p-(ω-N-acetylaminooctanoyl)phenyl]propionic acid, (160) 3-[p-(ω-N-acetylaminoheptanoyl) ) phenyl]propionic acid, (161) 3-[p-(ε-N-acetylaminocaproyl)phenyl]methyl propionate, (162) 3-[p-(δ-N-acetylaminovaleryl)phenyl] Methyl propionate, (164) 3-[p-(ε-N-acetylaminocaproyl)phenyl]butyl propionate, (165) 3-[p-(ω-N-acetylaminooctanoyl)phenyl]propionic acid Methyl, (166) 2-[p-(ε-N-acetylaminocaproyl)phenyl]acetic acid, (168) 4-[p-(ε-N-acetylaminocaproyl)phenyl]butyric acid, and these compounds Similarly, the following compounds are also exemplified. Compounds (100) to (104), (108) to (110),
(134), (140), (144), (156) ~ (160), (166
)
Sodium, potassium, calcium, and aluminum salts of ~(168). Also compounds (100)
~(120) is trans isomer regarding the cyclohexane ring,
It can be in the form of cis form or a mixture thereof. The compound represented by the above formula [] provided by the present invention can be produced as follows. Manufacturing method a According to the present invention, the following formula []-a [In the formula, R ¹ , X ¹ , ² and the same definitions as above. ] The aminocarboxylic acid derivative or its salt represented by the following formula [], R ¹ NHCH ₂ —X ¹ —CO—Hal … [] [wherein R ¹ and X ¹ are the same as defined above,
Hal represents a halogen atom. ] Aminocarboxylic acid halide represented by and the following formula [] [In the formula, X ² is the same as the above definition, and R ⁴¹ is -
COOR ⁵¹ is represented and R ⁵¹ is an alkyl group having 1 to 6 carbon atoms. ] The compound represented by the following is produced by subjecting it to an acylation reaction in the presence of a Lewis acid, and then subjecting it to hydrolysis and/or salt-forming reaction as required. In the above formula [], the definitions of R ¹ and X ¹ are the same as in the above formula [], and Hal represents a halogen atom, preferably a chlorine atom or a bromine atom. The aminocarboxylic acid halide represented by the above formula [] can be produced by a known method of reacting the corresponding aminocarboxylic acid with a halogenating agent such as thionyl chloride, phosphorus trichloride, or phosphorus pentachloride. In the above formula [] which is the other raw material, X ²
is the same as in the above formula [], and R ⁴¹ is -
Represents COO ⁵¹ . Here, R ⁵¹ is an alkyl group having 1 to 6 carbon atoms. Examples of such alkyl groups can be the same as those exemplified in the above formula []. Examples of the aminocarboxylic acid halide represented by the above formula [] include the following. 4-N-acetylaminomethylcyclohexanecarboxylic acid chloride, 4-N-acetylaminomethylcyclohexanecarboxylic acid bromide, 4-N-acetylaminomethylbenzoic acid chloride, ε-N-acetylaminocaproic acid chloride, represented by the above formula [] The following compounds may be mentioned. Methyl 3-phenylpropionate, Ethyl 3-phenylpropionate, Methyl 4-phenylbutyrate, Ethyl 4-phenylbutyrate The above acylation reaction of the present invention is performed by combining an aminocarboxylic acid halide of the above formula [] with an aminocarboxylic acid halide of the above formula []. ] in the presence of a Lewis acid. Examples of Lewis acids include aluminum halide compounds such as aluminum chloride and aluminum bromide; zinc halide compounds such as zinc chloride; iron halide compounds such as ferric chloride; tin halide compounds such as stannic chloride; Alternatively, halogenated titanium compounds such as titanium chloride can be cited as preferred. Among these, aluminum halide compounds and zinc halide compounds are particularly preferably used. The reaction is stoichiometrically a condensation reaction between 1 mole of the aminocarboxylic acid halide of the general formula [] and 1 mole of the compound of the general formula [], but if either one is used in a larger amount than the stoichiometric amount, There is nothing wrong with using it. Generally, one can be used in an acceptable quantitative ratio of 0.1 to 10 times the other. Since the reaction proceeds without heat generation, the Lewis acid is preferably used in an amount of about 1 to about 20 mol, more preferably about 1.5 mol, per mol of one of the raw materials used, which has a smaller quantitative proportion. It is used in a proportion of from about 10 mol to about 10 mol, particularly preferably from about 2 to about 5 mol. If the compound of general formula [] exhibits a liquid state under the reaction conditions, the presence of a reaction medium is not essential for the reaction to proceed, but the reaction is preferably carried out in the presence of a reaction medium. The reaction medium is preferably an aprotic inert organic solvent, such as chloroform, carbon tetrachloride, dichloromethane, dichloroethane, tetrachloroethane, dibromoethane,
Halogenated hydrocarbons such as bromobenzene and chlorobenzene; hydrocarbons such as hexane, heptane, cyclohexane, and ligroin; or nitrobenzene, carbon disulfide, and the like are used. The reaction is preferably carried out at a temperature usually between about 0°C and the reflux temperature of the reaction system. Particular preference is given to carrying out at temperatures between room temperature and 80°C. In carrying out the reaction, the mixture of aminocarboxylic acid halide and Lewis acid in the reaction medium is
The compound of the above formula [] is added, or the Lewis acid is added in small portions to the mixture of the aminocarboxylic acid halide and the compound of the above formula [] in the reaction medium, or the compound of the above formula [] and the Lewis acid are added. Adding the aminocarboxylic acid halide to the mixture in the reaction medium is preferably employed. Among these, the first operation is particularly preferably adopted. The reaction usually completes in about 5 minutes to about 24 hours. After the above acylation reaction, the target product is isolated and purified as follows. That is, water or sodium hydroxide, potassium hydroxide, sodium carbonate,
First, the Lewis acid is decomposed by adding an aqueous solution of a basic compound such as potassium carbonate. Thereafter, when the reaction solvent becomes an extraction solvent, the product may be separated as a solution of the reaction solvent. When the reaction solvent is an extraction solvent and cannot be used as a solvent, the reaction solvent is removed and extracted with a water-immiscible organic solvent such as ether, chloroform, carbon tetrachloride, dichloroethane, benzene, toluene, xylene, etc., or the reaction is A water-immiscible organic solvent and water may be added to the residue obtained by removing the solvent and water for extraction. The extracted and separated organic layer is then washed with water, dried and concentrated to give the desired product. The target product is obtained as a compound of formula []-a in which R ¹ corresponds to a protecting group such as an acyl group, and R ⁴ is R ⁴¹ . (i) The compound thus obtained is further subjected to a hydrolysis reaction of the ester group (-COOR ⁵¹ ), if necessary. Such hydrolysis is carried out by a method known per se using an acid or an alkali as a catalyst. When an acid is used as a catalyst, the formula [] -
In a, R ¹ is an acyl group, and R ⁴ -
An aminocarboxylic acid derivative which is COOH is obtained. Acid catalysts include hydrochloric acid, hydrobromic acid, sulfuric acid,
Examples include inorganic acids such as phosphoric acid; organic carboxylic acids such as acetic acid, propionic acid, and maleic acid; and organic sulfonic acids such as methanesulfonic acid and benzenesulfonic acid. After acid-catalyzed hydrolysis, to obtain the product, the reaction mixture is usually evaporated to dryness, water is added to the resulting residue, extracted with an organic solvent, and the resulting organic layer is extracted with the usual The target product is separated by a method, or the residue is directly recrystallized, or the residue is subjected to chromatography. When an alkali is used as a catalyst, a compound is produced in which R ¹ is an acyl group or , and R ⁴ is a carboxyl group in the form of a salt in the formula []-a. As an alkali catalyst, sodium hydroxide,
Examples include sodium carbonate, sodium hydrogen carbonate, potassium hydroxide, potassium carbonate, and the like. When using an alkali catalyst, to obtain the desired product, an acid is usually added to the reaction mixture to neutralize the carboxyl group in the salt form and convert the carboxylate group to -COOH, and then the acid catalyst is added. The same operation as the above conditions for separating the target product from the reaction mixture used may be performed. (ii) The compound thus obtained is further subjected to a salt-forming reaction, if necessary. That is, to obtain a compound in the form of a salt in which R ⁴ is -COOH, a compound of formula []-a in which R ⁴ is -COOH is subjected to a neutralization reaction with a basic compound such as that used in the above-mentioned alkali catalyst. Then, the reaction mixture is evaporated to dryness, and the residue may be subjected to reconsolidation or chromatography as appropriate. The aminocarboxylic acid derivative of the present invention thus produced is a useful compound expected to be used in pharmaceuticals such as anti-ulcer agents. Hereinafter, the present invention will be explained in more detail with reference to Examples. Example 1 Synthesis of methyl 3-[p-(trans-4-N-acetylaminomethylcyclohexylcarbonyl)phenyl]propionate (trans(112)) 3 g of trans-4-N-acetylaminomethylcyclohexanecarboxylic acid chloride was carbon sulfide
The suspension was suspended in 50 ml of water, and 5.5 g of aluminum chloride was added under ice-cooling with vigorous stirring, followed by a solution of 23 g of methyl phenylpropionate and 30 ml of carbon disulfide, and the mixture was stirred under reflux for 25 hours. After the reaction was completed, the solvent was distilled off, water was added to the residue, and the mixture was extracted with chloroform. Wash the chloroform layer with water,
After drying over anhydrous sodium sulfate, the chloroform was distilled off under reduced pressure to obtain a pale yellow amorphous substance. This product was purified by column chromatography using silica gel as a carrier (elution solvent: mixed solvent of chloroform and ethyl acetate) to obtain 3.0 g of the desired trans(112) (yield: 63%).
I got it. This material has the following physical properties and supports the structure. NMR (CDCl ₃ ), δ (ppm): 7.85 (2H, d, J = 8.5Hz, benzene ring Hs), 7.25 (2H, d, J = 8.5Hz, benzene ring Hs), 5.85 (1H, m, [ [Formula]), 3.65 (3H, s, -COOC H ₃ ), 2.3-3.4, 1.0-2.2 (16H, m, -C H ₂ - and cyclohexane ring Hs), 2.0 (3H, s, [Formula]), Example 2 Synthesis of 3-[p-(trans-4-N-acetylaminomethylcyclohexylcarbonyl)phenyl]propionic acid (trans(100)) 1 g of trans(112) obtained in Example 1 was added to 2N
The suspension was suspended in 30 ml of hydrochloric acid and a hydrolysis reaction was carried out at room temperature for 48 hours. After the reaction is complete, hydrochloric acid is distilled off under reduced pressure, and the resulting residue is isolated and purified using Preparalive thin layer chromatography to obtain the desired trans(100).
845 mg (yield 88%) was obtained. This material has the following physical properties and supports the structure. NMR (MeOH-d ₄ ), δ (ppm): 7.8 (2H, d, J = 8.5Hz, benzene ring Hs), 7.25 (2H, d, J = 8.5Hz, benzene ring Hs), 2.0 (3H, s , [Formula]), 1.0 to 3.4 (16H, m, cyclohexane ring and -C
H ₂ -), Example 3 3-Synthesis of methyl [p-(ε-N-acetylaminocaproyl)phenyl]propionate (161) ε-N-acetylaminocaproic acid was reacted with thionyl chloride in benzene. Manufactured ε-N-
Suspend 800 mg of acetylaminocaproic acid chloride in 20 ml of carbon disulfate, add 1.3 g of aluminum chloride under ice cooling with vigorous stirring, then add a solution of 550 mg of phenylpropionate methyl ester and 5 ml of carbon disulfide, and reflux. The mixture was stirred for 4 hours. After the reaction is complete, the carbon disulfide layer is separated by decantation, and a small amount of ice water is carefully added to the residue to decompose excess aluminum chloride. Furthermore, an aqueous sodium hydroxide solution was added to the obtained aqueous solution to dissolve the resulting aluminum hydroxide, and then extracted three times with chloroform. After washing the chloroform layer with water and drying over anhydrous sodium sulfate, the chloroform was distilled off under reduced pressure to obtain 900 mg of a white oily substance. This material has the following physical properties, 3-[p-(ε
It was identified as methyl -N-acetylaminocaproyl)phenyl]propionate (161). NMR (CDCl ₃ ): δ (ppm): 7.85 (2H, d, J = 8.5Hz, benzene ring Hs), 7.25 (2H, d, J = 8.5Hz, benzene ring Hs), 3.6 (3H, s, [ [Formula]), 2.2-3.5 (8H, m, C H ₂ -), 1.95 (3H, s, [Formula]) 1.3-1.8 (6H, m, -C H ₂ -), Example 4 3- [p -(ω-N-acetylaminooctanoyl)phenyl]methyl propionate (165)
Synthesis of ω-N-acetylaminocapric acid chloride
Suspend 500 mg in 20 ml of carbon disulfide, add 1 g of aluminum chloride under ice cooling with vigorous stirring, and then add phenylpropionate methyl ester 374.
Add a solution of 10 mg and 10 ml of carbon disulfide and reflux.
The reaction was allowed to proceed for 3.5 hours. After the reaction was completed, the solvent was distilled off, water was added to the residue, and the mixture was extracted with chloroform. The chloroform layer is treated according to a conventional method, and the resulting residue is purified by column chromatography (elution solvent: chloroform) and used for the purpose (165)
545 mg (yield: 69%) was obtained. This material has the following physical properties and supports the structure. NMR (CDCl ₃ ), δ (ppm) 7.85 (2H, d, J = 8.5Hz, benzene ring Hs), 7.25 (2H, d, J = 8.5Hz, benzene ring Hs), 3.6 (3H, s, [Formula ]), 1.3-3.5 (18H, m, methylene), 2.0 (3H, s, [formula]), Example 5 3-[p-(ω-N-acetylaminooctanoyl)phenyl]propionic acid (159) Synthesis of 300 mg of methyl 3-[p-(ω-N-acetylaminooctanoyl)phenyl]propionate (165) obtained in Example 4 was treated in the same manner as in Example 2 and purified to obtain the desired product (159). ) 227 mg (yield: 79
%) was obtained. This material has the following physical properties and supports the structure. NMR (MeOH-d ₄ ), δ (ppm): 7.95 (2H, d, J = 8.5Hz, benzene ring Hs), 7.32 (2H, d, J = 8.5Hz, benzene ring Hs), 1.0-3.2 (18H , m, methylene), 2.0 (3H, s, [formula]), Example 6 Synthesis of 3-[p-(δ-N-acetylaminovaleryl)phenyl]methyl propionate (162) δ-N-acetyl Aminovaleryl chloride
400 mg was suspended in carbon disulfide, 1 g of aluminum chloride was added under ice-cooling with vigorous stirring, and then a solution of 369 mg of methyl phenylpropionate and 5 ml of carbon disulfide was added and reacted under reflux for 2 hours. . Thereafter, the same treatment as in Example 4 was carried out to obtain 657 mg (yield: 52%) of the desired (162). This material has the following physical properties and supports the structure. NMR (CDCL ₃ ), δ (ppm): 7.85 (2H, d, J = 8.5Hz, benzene ring Hs), 7.25 (2H, d, J = 8.5Hs, benzene ring Hs), 3.65 (3H, s, [ 1.0-3.3 (12H, m, methylene), 2.0 (3H, s, [formula]), Example 7 3-[p-(4-N-acetylaminomethylbenzoyl)phenyl]methyl propionate ( Synthesis of 136) 1.0 g of 4-N-acetylaminomethylbenzoic acid chloride produced by reacting 4-N-acetylaminomethylbenzoic acid with thionyl chloride was suspended in 30 ml of carbon disulfide, and cooled on ice while stirring vigorously. After adding 1.9 g of aluminum chloride to the bottom, a solution of 776 mg of methyl phenylpropionate and 10 ml of carbon disulfide was added and stirred under reflux for 4 hours.
After the reaction is complete, the carbon disulfide layer is separated by decantation, and a small amount of ice water is carefully added to the residue to decompose excess aluminum chloride. It was then extracted three times with ethyl acetate. The ethyl acetate layer was washed with a 1N aqueous sodium hydroxide solution, then water, and dried over anhydrous sodium sulfate. Ethyl acetate was distilled off under reduced pressure to obtain 1122 mg of a yellow oil. This product had the following physical properties and was identified as (136). NMR (CDCl ₃ ), δ (ppm): 7.2-7.8 (8H, m, benzene ring Hs), 4.4 (2H, d, J = 6Hz, -NH- CH ₂ -), 3.6 (3H, s, [ [Formula]), 2.4-3.2 (4H, m, -C H ₂ -), 2.0 (3H, s, [Formula]), Example 8 2-[p-(4-N-acetylaminomethylbenzoyl)phenyl] Synthesis of methyl acetate (142) 1.0 g of 4-N-acetylaminomethylbenzoic acid chloride was suspended in 35 ml of carbon disulfide, and 20 g of aluminum chloride was added under ice-cooling with vigorous stirring, followed by 709 mg of phenylacetic acid mether ester. A solution of 15 ml of carbon disulfide was added and stirred under reflux for 4 hours. Thereafter, the same procedure as in Example 7 was carried out to obtain 753 mg (yield: 49%) of the desired (142) having the following physical properties. NMR (CDCl ₃ ), δ (ppm): 7.1-7.9 (8H, m, benzene ring Hs), 4.4 (2H, d, J = 6Hz, -NH- CH ₂ -), 3.6 (3H, s, [ [Formula]), 3.55 (2H, s, -CH ₂ -), 2.0 (3H, s, [Formula]),

Claims (1)

[Claims] 1. The following formula [] [In the formula, R ¹ represents an acyl group having 1 to 7 carbon atoms, and X ¹ represents an alkylene group having 3 to 6 carbon atoms, 1,4
-Represents a cyclohexylene group or a 1,4-phenylene group, R ² and R ³ together represent an oxo group, X ² represents an alkylene group having 1 to 6 carbon atoms, and R ⁴ represents -COOR ⁵ In the formula, R ⁵ is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms. ] An aminocarboxylic acid derivative or a salt thereof. 2. The aminocarboxylic acid derivative or salt thereof according to claim 1, wherein R ¹ in the above formula [] is an acetyl group. 3. The aminocarboxylic acid derivative or salt thereof according to claim 1 or 2, wherein in the above formula [], X ² is a methylene group or a dimethylene group. 4 The following formula [] R ¹ NHCH ₂ -X ¹ -CO-Hal... [] [In the formula, R ¹ represents an acyl group having 1 to 7 carbon atoms, X ¹ represents an alkylene group having 3 to 6 carbon atoms, 1 ,4
-Represents a cyclohexylene group or a 1,4-phenylene group, and Hal represents a halogen atom. ] Aminocarboxylic acid halide represented by and the following formula [] [In the formula, X ² represents an alkylene group having 1 to 6 carbon atoms, R ⁴¹ represents -COOR ⁵¹ , and R ⁵¹ represents an alkylene group having 1 to 6 carbon atoms.
~6 alkyl group. ] The following formula [ ] characterized by causing an acylation reaction with a compound represented by in the presence of a Lewis acid.
-a [In the formula, R ¹ , X ¹ , X ² and R ⁴¹ are the same as defined above. ] A method for producing an aminocarboxylic acid derivative or a salt thereof.