Method for preparing esteramide compounds

Abstract

The present invention relates to a method for preparing esteramide compounds.

Description

[Technical Field]

[0001] This application claims priority under European Patent Application No. 23167672.7, filed on 13 April 2023, and the entire contents of this application are incorporated herein by reference for all purposes. [Background technology]

[0002] The present invention relates to a method for preparing esteramide compounds.

[0003] Esteramide compounds are useful solvents / coagulants in a variety of plant protection, cleaning, degreasing, stripping, lubrication, coating, and pigment / ink compositions. Corresponding compositions are described in U.S. Patent No. 8,735,324, which also describes a method for preparing esteramide compounds by reacting diester compounds with amines.

[0004] In currently used industrial processes, the required diesters are obtained, for example, as described in U.S. Patent No. 9,267,015, by reacting a mixture of adiponitrile, 2-methylglutaronitrile, and 2-ethylsuccinonitrile (a by-product of adiponitrile synthesis) with water under acidic conditions to produce a mixture of diacid intermediates, which are then esterified in a second step using methanol to obtain a mixture of dimethyl 2-methylglutarate, dimethyl 2-ethylsuccinate, and dimethyl adipate.

[0005] However, this synthetic approach has the drawback of yielding a mixture of diacitic esters and, consequently, esteramide compounds. As a result, if a pure esteramide compound, such as pure methyl 5-(dimethylamino)-2-methyl-5-oxopentanoate, is desired, a complicated purification process is required. Furthermore, if the mixture is used as is, its recycling becomes more difficult. [Overview of the project]

[0006] Therefore, an object of the present invention is to provide a method for obtaining high-purity esteramide compounds. A further object is to provide a method for preparing esteramide compounds in good yield, preferably starting from readily available starting compounds. Yet another object is to provide a method for preparing esteramide compounds that generates little waste and aqueous effluent and exhibits excellent atomic efficiency.

[0007] This time, it was found that these and other problems can be solved by the method according to the present invention. The present invention relates to an esteramide compound of formula (IV): [ka] (In the formula, R is an alkyl group, R 3 and R 4 R is selected from hydrocarbon groups having an average number of carbon atoms in the range of 1 to 36, which are the same or different, and each is saturated or unsaturated, linear or branched, may be optionally cyclic, optionally aromatic, and optionally substituted, 3 and R 4 (These may optionally come together to form a ring member that may be optionally substituted and / or optionally contain heteroatoms.) A method for preparing, i) Alkyl alkylate of formula (I) [ka] (In the formula, R is as defined above.) Dimerizing it gives the dimer of formula (II) [ka] (In the formula, R is as defined above.) The process of obtaining; ii) Hydrogenate the dimer of formula (II) to obtain the compound of formula (III). [ka] (wherein R is as defined above) a step of obtaining; and iii) reacting a compound of formula (III) with an amine of formula HNR 3 R 4 (wherein R 3 and R 4 are as defined above); relates to a method comprising.

[0008] The present invention is based on the recognition that a diester intermediate in the conventional synthesis of an ester amide compound can be obtained in high purity by an efficient process for producing an alkyl alkyl acid dimer that is easily hydrogenatable. Therefore, the ester amide compound obtained after amidation of such a diester intermediate can be prepared in high purity and good yield from readily available starting compounds, such as alkyl alkyl acids, particularly methyl acrylate.

Mode for Carrying Out the Invention

[0009] According to the present invention, the term "about" means ±10%, preferably ±5%, most preferably ±2% of the specified numerical value.

[0010] The present invention provides an ester amide compound of formula (IV):

Chemical Formula

[0011] In one embodiment, the dimerization step i) is performed using a catalyst of formula (V). [ka] (In the formula, R 1 and R 2 They are either the same or different, an aliphatic group, or together with an N atom to form a heteroaliphatic ring. R a It is a hydrocarbyl group, R b is an aliphatic group or NR 5 R 6 And R 5 and R 6 (This means they are the same or different, are aliphatic groups, or form a heteroaliphatic ring together with an N atom.) It is carried out in the presence of others.

[0012] In further embodiments, the dimerization step i) is carried out in the presence of compound A, which is a tertiary alcohol or silanol, preferably a tertiary alcohol such as tert-butanol, tert-amyl alcohol, or pinacol, more preferably tert-butanol.

[0013] Preferably, in a method for producing the dimer of formula (II) as defined herein, the molar ratio of [compound A] / [alkyl acrylate of formula (I)] is selected from about 4:1 to about 0.01:1, preferably about 2:1 to about 0.1:1, more preferably about 0.5:1 to about 0.1:1, and particularly about 0.5:1 to about 0.2:1.

[0014] Preferably, in a method for producing the dimer of formula (II) as defined herein, R is C1 to C 18 More preferably, C1-C8 alkyl groups, and even more preferably C1-C4 alkyl groups.

[0015] Preferably, in a method for producing the dimer of formula (II) as defined herein, R is a methyl group, ethyl group, propyl group, isopropyl group, n-butyl group, sec-butyl group, isobutyl group, tert-butyl group, pentyl group, hexyl group, 2-ethylhexyl group, octyl group, decyl group, dodecyl group, t-dodecyl group, tetradecyl group, hexadecyl group, or octadecyl group; more preferably a methyl group, ethyl group, isopropyl group, butyl group, or 2-ethylhexyl group; even more preferably a methyl group, ethyl group, isopropyl group, or butyl group; and most preferably a methyl group.

[0016] Preferably, in a method for producing the dimer of formula (II) as defined herein, R 1 and R 2 This is an identical linear or branched alkyl group containing 1 to 6 carbon atoms, more preferably 1 to 3 carbon atoms, and most preferably ethyl.

[0017] Preferably, in a method for producing the dimer of formula (II) as defined herein, R 1 and R 2 Together with the N atom, it forms a heteroaliphatic ring containing 3 to 5 carbon atoms, preferably 4 carbon atoms.

[0018] Preferably, in a method for producing the dimer of formula (II) as defined herein, R a is either an aromatic group or an aliphatic group, more preferably an aromatic group, and even more preferably selected from phenyl, tolyl, xylyl, mesityl, duryl, pentamethylphenyl, 2,6-diisopropylphenyl, tert-butylphenyl, ditert-butylphenyl, methoxyphenyl, dimethoxyphenyl, methoxytolyl, methylenedioxyphenyl, biphenyl, nitrophenyl, halogen-substituted phenyl, trifluoromethylphenyl, naphthyl, pyridyl, furyl, pyrrolyl, thiophenyl, 2-indolyl, benzofuryl, and all of these positional isomers.

[0019] Preferably, R aPhenyl; ortho-, meta-, or para-tolyl; xylyl including all positional isomers, e.g., 2,3-dimethylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4-dimethylphenyl, and 3,5-dimethylphenyl; 3-methyl-4-methoxyphenyl, 2-methyl-4-methoxyphenyl, 2-methyl-3-methoxyphenyl, 4-methyl-3-methoxyphenyl, 5-methyl-3-methoxyphenyl, 6-methyl-3-methoxyphenyl, 2-methoxy-3-methylphenyl, 2- Methoxy-4-methylphenyl, 2-methoxy-5-methylphenyl, 2-methoxy-6-methylphenyl; Mesityl containing all positional isomers, e.g., 2,3,4-trimethylphenyl, 2,3,5-trimethylphenyl, 2,3,6-trimethylphenyl, 2,4,5-trimethylphenyl, 2,4,6-trimethylphenyl, and 3,4,5-trimethylphenyl; Duryl containing all positional isomers, e.g., 2,3,4,5-tetramethylphenyl, 2,3,4,6-tetramethylphenyl, and 2,3,5,6-tetramethylphenyl; Pentamethylphenyl, 2,6-diisopropylphenyl; ortho-, meta-, or para-tert-butylphenyl; 2,3-di-tert-butylphenyl, 2,4-di-tert-butylphenyl, 2,5-di-tert-butylphenyl, 2,6-di-tert-butylphenyl, 3,4-di-tert-butylphenyl, and 3,5-di-tert-butylphenyl; ortho-, meta-, or para-methoxyphenyl; ortho-, meta-, or para-chlorophenyl; 2,3-dimethoxyphenyl, 2,4-dimethoxyphenyl Nyl, 2,5-dimethoxyphenyl, 2,6-dimethoxyphenyl, 3,4-dimethoxyphenyl, and 3,5-dimethoxyphenyl; 2,3-methylenedioxyphenyl, 3,4-methylenedioxyphenyl; ortho-, meta-, or para-nitrophenyl; ortho-, meta-, or para-biphenyl; ortho-, meta-, or para-trifluoromethylphenyl, ortho-, meta-, or para-fluorophenyl; 1- or 2-naphthyl; 2-pyridyl, 3-pyridyl, or 4-pyridyl; 2-furyl, 3-furyl;Selected from 1-pyrrolyl, 2-pyrrolyl, or 3-pyrrolyl; 2-thiophenyl, 3-thiophenyl; 2-indolyl, 3-indolyl, 2-benzofuryl, and 3-benzofuryl; preferably phenyl; ortho-, meta-, or para-tolyl; or xylyl and its positional isomers.

[0020] Preferably, in a method for producing the dimer of formula (II) as defined herein, R b is NR 5 R 6 And R 5 and R 6 They are the same or different, are aliphatic groups, or form a heteroaliphatic ring together with the N atom, more preferably R 5 and R 6 This refers to an identical linear or branched alkyl group containing 1 to 6 carbon atoms, more preferably 1 to 3 carbon atoms, and most preferably ethyl.

[0021] Preferably, in a method for producing the dimer of formula (II) as defined herein, R a is phenyl, and R 1 and R 2 is ethyl, and R b is NR 5 R 6 And R 5 and R 6 It is ethyl.

[0022] Preferably, in a method for producing the dimer of formula (II) as defined herein, the catalyst of formula (V) is a compound of formulas (VIII) to (XIV): [ka] It is a compound selected from the group consisting of the following:

[0023] More preferably, in a method for producing the dimer of formula (II) as defined herein, the catalyst of formula (V) is a compound selected from the group consisting of compounds of formulas (IX) and (XI) to (XIV), more preferably selected from compounds of formulas (XI), (XII), and (XIV), even more preferably selected from the group consisting of compounds of formulas (XI) and (XIV), and most preferably the catalyst of formula (V) is a compound of formula (XIV).

[0024] Preferably, in a method for producing the dimer of formula (II) as defined herein, step i) of dimerization is carried out in an organic solvent, more preferably in an aprotic solvent, and even more preferably in an organic solvent selected from tetrahydrofuran (THF), 2-methyltetrahydrofuran (MeTHF), toluene, xylene, anisole, diethyl ether, tert-butyl methyl ether (MTBE), dichloromethane (DCM), chloroform, 1,4-dioxane, pentane, cyclopentane, hexane, cyclohexane, methylcyclohexane, benzene, and acetonitrile, even more preferably from MeTHF, anisole, and toluene, and most preferably from MeTHF and anisole.

[0025] Preferably, in a method for producing the dimer of formula (II) as defined herein, the dimerization step i) is carried out at a temperature in the range of about 20°C to about 120°C, more preferably about 20°C to about 80°C, even more preferably about 25°C to about 60°C, and most preferably about 30°C to about 60°C.

[0026] Preferably, in the method for producing the dimer of formula (II) as defined herein, the catalyst of formula (V) in step i) is used in an amount of 0.20 mol% to 1.00 mol%, more preferably about 0.25 mol% to about 0.90 mol%, even more preferably about 0.30 mol% to about 0.90 mol%, even more preferably about 0.30 mol% to about 0.80 mol%, even more preferably about 0.30 mol% to about 0.70 mol%, even more preferably about 0.30 mol% to about 0.60 mol%, and most preferably about 0.30 mol% to 0.50 mol% relative to the alkyl acrylate of formula (I).

[0027] Preferably, in a method for producing the dimer of formula (II) as defined herein, the dimerization step i) is carried out under anhydrous conditions and in the absence of oxygen.

[0028] Preferably, the method for producing the dimer of formula (II) as defined herein is a compound of formula (IV). [ka] (In the formula, X is a chloride, bromide, or iodide, preferably a chloride. R a It is a hydrocarbyl group, R c X(R b The NR defined above 5 R 6 (In the case of a catalyst of formula (V)) or R b (R b (In the case of a catalyst of formula (V) where is an aliphatic group) of, - R 1 R 2 NH (in the formula, R 1 and R 2 R c R b The case is as defined above) an amine, or - Formula R 1 R 2 Amines of NH and formula R 5 R 6 Both NH amines (wherein R in the formula) 5 and R 6 R c (As defined herein for the case where X is...) The process further includes a first step 0) of preparing the catalyst of formula (V) by reacting with .

[0029] Preferably, in a method for producing the dimer of formula (II) as defined herein, steps 0) and i) are consecutive steps carried out after step 0) without isolating the catalyst.

[0030] Preferably, in a method for producing the dimer of formula (II) as defined herein, R c X is X.

[0031] Preferably, in a method for producing the dimer of formula (II) as defined herein, step 0) is carried out in an organic solvent, more preferably in an aprotic solvent, and even more preferably in an organic solvent selected from tetrahydrofuran (THF), 2-methyltetrahydrofuran (MeTHF), toluene, xylene, anisole, diethyl ether, tert-butyl methyl ether (MTBE), dichloromethane (DCM), chloroform, 1,4-dioxane, pentane, cyclopentane, hexane, cyclohexane, methylcyclohexane, benzene, and acetonitrile, even more preferably from MeTHF, anisole, and toluene, and most preferably from MeTHF and anisole.

[0032] Preferably, in a method for producing the dimer of formula (II) as defined herein, step 0) is carried out at a temperature in the range of about 20°C to about 100°C, preferably about 20°C to 80°C, more preferably about 25°C to 60°C, and most preferably about 40°C.

[0033] Preferably, in a method for producing the dimer of formula (II) as defined herein, step 0) is a process of providing amine R in an aprotic solvent. 1 R 2 The reaction is carried out by slowly adding the reactant of formula (IV) to a solution of NH, where the amine is R in formula (VI). c R b And R b If is an aliphatic group, it is used in an amount of 2 equivalents or more relative to the reactant of formula (VI). Step (0) is to dissolve amine R in an aprotic solvent. 1 R 2 NH and R 5 R 6 This can also be carried out by slowly adding the reactants of formula (VI) to a solution containing both NH, where the total amount of amine is R in (VI). cIf X is true, then the amount is 4 equivalents or more relative to the reactants in equation (VI).

[0034] Preferably, in a method for producing the dimer of formula (II) as defined herein, step 0) is carried out under anhydrous conditions and in the absence of oxygen.

[0035] Preferably, in a method for producing the dimer of formula (II) as defined herein, step 0) includes a filtration step to remove a by-product which is an ammonium halide formed before carrying out step i).

[0036] Furthermore, the present invention provides a method for producing a dimer of formula (II) as defined herein, and a subsequent method for hydrogenating the dimer of formula (II) obtained in the dimerization step, preferably using H2 and a hydrogenation catalyst, to produce a compound of formula (III). [ka] (In the formula, R is as defined above.) The process includes step ii) obtaining and step iii) producing a compound of formula (III), wherein the hydrogenation catalyst is, for example, a Pd-based catalyst, e.g., Pd / C, Pd / Al2O3, Pd / SiO2, a Ru-based catalyst, e.g., Ru / C, a Pt-based catalyst, e.g., Pt / C, a Ni-based catalyst, e.g., supported nickel or Raney nickel catalyst, a Co-based catalyst, e.g., supported cobalt or Raney cobalt, a Rh-based catalyst, e.g., Rh / C, an Ir-based catalyst, e.g., Ir / C, preferably Pd / C or Raney nickel, preferably Pd / C.

[0037] Furthermore, the method of the present invention involves using the compound of formula (III) with formula HNR 3 R 4 The process includes step iii) reacting with an amine, in which, R 3 and R 4 R is selected from hydrocarbon groups having an average number of carbon atoms in the range of 1 to 36, which are the same or different, and each is saturated or unsaturated, linear or branched, may be optionally cyclic, optionally aromatic, and optionally substituted,3 and R 4 may optionally together form ring members which may optionally be substituted and / or may optionally contain heteroatoms.

[0038] R 3 groups and R 4 groups may be the same or different and in particular may be groups selected from C1 - C 12 alkyl groups, aryl groups, alkaryl groups, arylalkyl groups, or phenyl groups. The R 3 group and the R 4 group may in particular be optionally substituted by a hydroxyl group.

[0039] R 3 and R 4 groups may be the same or different and in particular may be especially selected from methyl, ethyl, propyl (n - propyl), isopropyl, n - butyl, isobutyl, n - pentyl, amyl, isoamyl, hexyl, cyclohexyl, or 2 - hydroxyethyl groups. The R 3 group and the R 4 group may be such that they together with a nitrogen atom form a morpholine group, a piperazine group, a pyrrolidine group, or a piperidine group. According to certain embodiments, R 3 = R 4 = methyl, or R 3 = R 4 = ethyl, or R 3 = R 4 = 2 - hydroxyethyl. When R 3 = R 4 = methyl, favorable results may be obtained.

[0040] During step iii), preferably 0.7 - 1.5 moles, for example 0.8 - 1.2 moles, preferably 0.9 - 1.1 moles, preferably about 1 mole of amine per mole of the hydrogenated dimer of formula (III) is used. It is advantageous to operate with a slightly excess amount of amine, such as at least 1.05 moles of excess per mole of dimer, for example 1.05 - 1.1 moles of amine per mole of dimer.

[0041] Step iii) can be carried out in solution, for example, in a solvent such as toluene or alcohol. However, it is preferable to avoid the presence of water and to operate in a non-aqueous solution. During this step, it is possible to gradually remove, for example, the alcohol produced simultaneously, in order to promote the reaction. This removal may involve removing the solvent, for example, using an azeotropic mixture. After the separation of the alcohol, the removed solvent can be reintroduced into the process.

[0042] Step iii) is preferably carried out in the presence of a catalyst, particularly a base-type catalyst. For example, a methylate such as MeONa, a carbonate such as K2CO3 or Na2CO3, or a titanate such as titanium tetraethoxide can be used.

[0043] The esteramide compounds obtained by the method according to the present invention can be used, for example, as solvents, particularly as solvents for preparing agricultural chemical formulations.

[0044] If any disclosure of a patent, patent application, or publication incorporated herein by reference conflicts with the description of this application to such an extent that it obscures certain terms, the description herein shall prevail. [Examples]

[0045] Example 1: Dimerization of methyl acrylate Analytically pure dimethyl 2-methyleneglutarate was obtained using the basic protocol described in point A below and the specific conditions described in point B below. All the obtained products were finally mixed to prepare a single lot.

[0046] A. Basic Protocol: All reactions were carried out under an inert argon atmosphere in carefully dried vessels. Prior to each reaction, methyl acrylate and tert-butanol were dried using 4A molecular sieves, and tert-butanol was distilled under argon.

[0047] A1. Preparation of catalyst Bis(diethylamino)phenylphosphine was synthesized by gradually adding a solution of dichlorophenylphosphine (1 equivalent) in 2-methyltetrahydrofuran (Me-THF) to a solution of diethylamine (4 equivalents) in Me-THF over 1 hour while stirring (1400 rpm), during which time the temperature of the reaction medium was maintained below 40°C (exothermic reaction). Upon addition of dichlorophenylphosphine, a white precipitate corresponding to the by-product (in this case, diethylammonium chloride), which is an ammonium chloride salt, was formed. After the addition was complete, the mixture was stirred at ambient temperature, and the progress of the reaction was tracked by NMR.

[0048] After the formation of bis(diethylamino)phenylphosphine was complete (which required stirring at room temperature for 1 hour after the addition of dichlorophenylphosphine), the mixture was filtered.

[0049] A solution of (diisopropylamino)pyrrolidinophenylphosphine in 2-methyltetrahydrofuran (Me-THF) - Diisopropylamine (3 equivalents) was used instead of diethylamine. - The final reaction mixture was further stirred at room temperature, 1 equivalent of pyrrolidine was added to the reaction mixture, and the mixture was stirred for a further 1 hour at room temperature to complete the formation of bis(amino)phosphine. Except for one element, it was synthesized using the same method.

[0050] A2. Dimerization It is equipped with a temperature probe, a condenser, a mechanical stirrer (a propeller with four inclined plows), and a baffle, and • Distilled tert-butanol Methyl acrylate A solution of bis(diethylamino)phenylphosphine or (diisopropylamino)pyrrolidinophenylphosphine in 2-methyltetrahydrofuran (Me-THF) was added to a 500 mL double-jacketed reactor containing [the specified substance].

[0051] The reaction was tracked using 1H NMR. The conversion rate of methyl acrylate was estimated from the 1H NMR by integrating the methylene protons of the product with those of the starting material, methyl acrylate.

[0052] At the end of the reaction, volatile substances (t-BuOH, Me-THF, and unconverted methyl acrylate) were removed under vacuum. The target product (dimethyl 2-methyleneglutarate) was then subjected to vacuum distillation (160°C, 15 mbar) to obtain an analytically pure product. A high-boiling by-product (methyl acrylate oligomer) remained in the distillation vessel.

[0053] B. Specific conditions a) Dimerization of methyl acrylate in tert-butanol catalyzed by bis(diethylamino)phenylphosphine (initial amount of dichlorophenylphosphine precursor: 0.7 mol% relative to methyl acrylate) (1:4 v / v t-BuOH:methyl acrylate = 0.24 mol(t-BuOH) / mol(methyl acrylate)), at 45°C. (Similar at 30°C) b) Dimerization of methyl acrylate in tert-butanol catalyzed by bis(diethylamino)phenylphosphine (0.7 mol% dichlorophenylphosphine precursor relative to methyl acrylate) (1:8 v / v t-BuOH:methyl acrylate = 0.12 mol(t-BuOH) / mol(methyl acrylate)), 45°C. (Similar results at 30°C and 60°C). c) Dimerization of methyl acrylate in tert-butanol catalyzed by bis(diethylamino)phenylphosphine (0.9 mol% dichlorophenylphosphine precursor relative to methyl acrylate) (1:4 v / v t-BuOH:methyl acrylate = 0.24 mol(t-BuOH) / mol(methyl acrylate)), 30°C. d) Dimerization of methyl acrylate in tert-butanol catalyzed by (diisopropylamino)pyrrolidinophenylphosphine (0.4 mol% dichlorophenylphosphine precursor relative to methyl acrylate) (1:8 v / v t-BuOH:methyl acrylate = 0.12 mol(t-BuOH) / mol(methyl acrylate)), 60°C.

[0054] Example 2: Catalytic hydrogenation of dimethyl 2-methyleneglutarate to dimethyl 2-methylglutarate The substrate, dimethyl 2-methyleneglutarate, prepared in Example 1, was first placed in a 100 mL autoclave reactor equipped with a mechanical stirrer (Rushton turbine), followed by the addition of a Pd / C (3%) catalyst (powder, 51% water content, equivalent to 1 g wet and 0.49 g dry, 1.73% by weight relative to the substrate). The reactor was then sealed and purged three times with 20 bar nitrogen, followed by three times with 5 bar hydrogen. The reaction mixture was stirred at 1400 rpm, and the temperature of the reaction mixture was then set to 25°C. Subsequently, the reaction medium was stirred at 25°C and a hydrogen pressure of 3-6 bar (1400 rpm) for 3 hours, and hydrogen consumption was tracked over time.

[0055] Upon confirmation of the end of the reaction by the absence of hydrogen consumption, the reaction mixture was cooled to room temperature, stirring was stopped, and the autoclave was depressurized. The reactor was purged with nitrogen, the crude product was removed from the reactor, the catalyst was filtered, and this was reused in a second hydrogenation batch carried out at 80°C (H2 pressure of 3-6 bar) for 8 hours.

[0056] After filtering the catalyst, the product, dimethyl 2-methylglutarate, was obtained as a clear liquid. This was used as is.

[0057] Example 3: Conversion of dimethyl 2-methylglutarate to methyl 5-(dimethylamino)-2-methyl-5-oxopentanoate The reaction was carried out in a double-jacketed reactor equipped with a condenser, a mechanical stirrer, and a temperature probe. Before starting the synthesis, the reactor was first washed with deionized water (to remove acid), and then trace amounts of water were removed by refluxing dry methanol.

[0058] The following steps were then applied: 1) 298.39 g (1.71 mol, 1 equivalent) of dimethyl 2-methylglutarate from Example 2 was placed in a reactor at room temperature and stirring was started. 2) Subsequently, the reaction mixture was cooled to 6-9°C, and at the same time, the temperature inside the condenser was set to the same temperature. 3) Subsequently, 85.28 g (1.89 mol, 1.1 equivalents) of dimethylamine gas (DMA) was condensed in the reactor by blowing it in liquid phase. Since the absorption of DMA into dimethyl 2-methylglutarate is exothermic, it was necessary to maintain the temperature of the reaction mixture below 15°C by adjusting the temperature of the double jacket and the flow rate of the DMA gas. 4) After adding the specified amount of DMA to the reactor, the inlet line was flushed with nitrogen. 5) 13.2 g of a 28 wt% methanol solution of sodium methoxide (3.70 g of NaOMe, 0.068 moles, equivalent to 4 mol% relative to dimethyl 2-methylglutarate) was added to the reactor over approximately 10 minutes. To avoid boiling of the DMA, the temperature of the reaction mixture was controlled as much as possible (maintained below 10°C). 6) Next, the filling line was flushed with 20.08 g of dry methanol. This was added over a period of 30 minutes. 7) Next, the reaction mixture was stirred at 50°C, and the progress of the reaction was tracked over time by GC analysis. 8) After stirring at 50°C for 2 hours and 30 minutes, the concentration of the starting bis-ester in the reaction mixture was 1.14% by weight, and the concentration of methyl 5-(dimethylamino)-2-methyl-5-oxopentanoate was 91.54% by weight. 9) The reaction mixture was then allowed to cool to room temperature and removed from the reactor. 10) Subsequently, the base catalyst was neutralized by adding 4.075 g of H3PO4 (85 wt% aqueous solution), and the precipitated phosphate was separated by filtration. 11) The solid was washed several times with methanol. 12) At this stage, some sediment formed in the filtrate, but it was filtered again without methanol washing. Subsequently, the solvent (water and methanol) was distilled by vacuum distillation (80°C, 10 mbar) to finally recover 273.8 g of crude methyl 5-(dimethylamino)-2-methyl-5-oxopentanoate. This was filtered again to remove solid matter, yielding 268.49 g of clear liquid.

Claims

1. Esteramide compounds of formula (IV): 【Chemistry 1】 (In the formula, R is an alkyl group, R ３ and R ４ R is selected from hydrocarbon groups having an average number of carbon atoms in the range of 1 to 36, which are the same or different, and each is saturated or unsaturated, linear or branched, may be optionally cyclic, optionally aromatic, and optionally substituted, ３ and R ４ (These may optionally form together ring members that are optionally substituted and / or optionally contain heteroatoms.) A method for preparing, i) Alkyl acrylate of formula (I) 【Chemistry 2】 (In the formula, R is as defined above.) Dimerizing it gives the dimer of formula (II) 【Transformation 3】 (In the formula, R is as defined above.) The process of obtaining; ii) Hydrogenate the dimer of formula (II) to obtain the compound of formula (III). 【Chemistry 4】 (In the formula, R is as defined above.) The process of obtaining; and iii) Compound of formula (III), formula HNR ３ R ４ (In the formula, R ３ and R ４ The process of reacting with an amine (as defined above) A method that includes this.

2. The dimerization step i) is performed by a catalyst of formula (V). 【Transformation 5】 (In the formula, R １ and R ２ are the same or different and are aliphatic groups or together with the N atom form a heteroaliphatic ring, R ａ It is a hydrocarbyl group, R ｂ is an aliphatic group or NR ５ R ６ It is either R ５ and R ６ (They are the same or different, and are either aliphatic groups or, together with the N atom, form a heteroaliphatic ring.) The method according to claim 1, carried out in the presence of [something].

3. The method according to claim 1 or 2, wherein the dimerization step i) is carried out in the presence of compound A, which is a tertiary alcohol or silanol, preferably a tertiary alcohol such as tert-butanol, tert-amyl alcohol, or pinacol, more preferably tert-butanol.

4. The method according to claim 3, wherein the molar ratio [compound A] / [alkyl acrylate of formula (I)] is selected from about 4:1 to about 0.01:1, preferably about 2:1 to about 0.1:1, and more preferably about 0.5:1 to about 0.1:

1.

5. R is C １ ~C １８ Preferably C １ ~C ８ Alkyl, more preferably C １ ~C ４ The method according to any one of claims 1 to 4, wherein the alkyl, most preferably methyl.

6. R １ and R ２ The method according to any one of claims 2 to 5, wherein the alkyl group is the same linear or branched alkyl group having 1 to 6 carbon atoms, preferably 1 to 3 carbon atoms, and more preferably ethyl.

7. R １ and R ２ The method according to any one of claims 2 to 5, wherein the N atom forms a heteroaliphatic ring containing 3 to 5 carbon atoms, preferably 4 carbon atoms.

8. R ａ The method according to any one of claims 2 to 7, wherein the group is either an aromatic group or an aliphatic group, preferably an aromatic group, and more preferably selected from phenyl, tolyl, xylyl, mesityl, duryl, pentamethylphenyl, 2,6-diisopropylphenyl, tert-butylphenyl, ditert-butylphenyl, methoxyphenyl, dimethoxyphenyl, methoxytolyl, methylenedioxyphenyl, biphenyl, nitrophenyl, halogen-substituted phenyl, trifluoromethylphenyl, naphthyl, pyridyl, furyl, pyrrolyl, thiophenyl, 2-indolyl, benzofuryl, and all positional isomers thereof.

9. R ｂ However, NR ５ R ６ And R ５ and R ６ However, they are either the same or different, and are either an aliphatic group or form a heteroaliphatic ring with the N atom, preferably R ５ and R ６ The method according to any one of claims 2 to 8, wherein the alkyl group is the same linear or branched alkyl group having 1 to 6 carbon atoms, more preferably 1 to 3 carbon atoms, and most preferably ethyl.

10. R ａ is phenyl, and R １ and R ２ is ethyl, and R ｂ NR ５ R ６ And R ５ and R ６ The method according to any one of claims 2 to 9, wherein is ethyl.

11. The method according to any one of claims 1 to 10, wherein the dimerization in step i) is carried out in an organic solvent, preferably an aprotic solvent, more preferably in an organic solvent selected from tetrahydrofuran (THF), 2-methyltetrahydrofuran (MeTHF), toluene, xylene, anisole, diethyl ether, tert-butyl methyl ether (MTBE), dichloromethane (DCM), chloroform, dioxane, pentane, cyclopentane, hexane, cyclohexane, methylcyclohexane, benzene, and acetonitrile, and even more preferably from MeTHF and toluene.

12. The method according to any one of claims 1 to 11, wherein the dimerization step i) is carried out at a temperature in the range of about 20°C to about 120°C, preferably about 20°C to about 80°C, more preferably about 25°C to about 60°C.

13. R ３ and R ４ However, they may be the same or different, C １ ~C １２ The method according to any one of claims 2 to 12, wherein the alkyl, aryl, alkaryl, and arylalkyl groups are selected, and each of these may be optionally substituted with one or more hydroxyl groups.

14. The method according to any one of claims 1 to 13, wherein step iii) is carried out in an aqueous solution or a non-aqueous solution, preferably a non-aqueous solution.

15. The method according to any one of claims 1 to 14, wherein step iii) is carried out in the presence of a catalyst, preferably a base-type catalyst, more preferably a methylate, carbonate, or titanate.

Images