Method for producing 4-(hydroxymethylphosphinoyl)-2-oxobutanoic acid

Abstract

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Description

[0001] This application claims the priority of Chinese Patent Application No. 202511757134.2, filed with the China National Intellectual Property Administration on November 26, 2025, and titled “METHOD FOR PRODUCING 4-(HYDROXYMETHYLPHOSPHINOYL)-2-OXOBUTANOIC ACID”, which is incorporated herein by reference in its entirety. FIELD

[0002] The present disclosure relates to the field of biochemical engineering, and in particular to a method for producing 4-(hydroxymethylphosphinoyl)-2-oxobutanoic acid. BACKGROUND

[0003] 4-(hydroxymethylphosphinoyl)-2-oxobutanoic acid, abbreviated as PPO or keto acid, is an important intermediate in the synthesis process of glufosinate. Using this compound as a starting material, glufosinate can be successfully produced through subsequent key steps such as reductive amination. In addition, it can also be efficiently converted into L-glufosinate, which has greater application value, by means of enzymatic catalysis.

[0004] In 1980, FBC Company proposed a production method in patent US4399287A, in which 20 3-(ethoxymethylphosphinoyl)propanoate was subjected to a Claisen condensation reaction to extend the carbon chain, thereby obtaining a 4-(hydroxymethylphosphinoyl)-2-oxobutanoic acid intermediate. However, the isolated yield of the target product was only about 30%, making it difficult to meet the output demands for large-scale industrial production.

[0005] Patent CN105218579A introduces a synthetic route using 25 4-(ethoxymethylphosphinoyl)-2-acetoxybutanenitrile as a raw material. In this route, 4-(hydroxymethylphosphinoyl)-2-hydroxybutanoic acid is first prepared by hydrolysis with hydrochloric acid. The resulting product is then neutralized with sodium hydroxide to form the corresponding salt, which is subsequently oxidized with an aqueous sodium hypochlorite solution in the presence of a transition-metal oxide catalyst to obtain disodium 15 2026237992   22 Sep 2026 4-(hydroxymethylphosphinoyl)-2-oxobutanoate. Finally, hydrogen chloride gas is introduced to remove the salts, thereby obtaining the target product. However, this method has problems in that a large amount of acid and base needs to be used and a large amount of by-product salts are generated, and the use of noble metal catalyst further increases production costs, while treatment of the by-product salts also becomes a difficult problem.

[0006] In summary, although various methods for producing 4-(hydroxymethylphosphinoyl)-2-oxobutanoic acid currently exist, these methods generally have problems such as low yield, high cost, harsh reaction conditions, and severe environmental pollution. It is an object of the present invention to substantially overcome or ameliorate at least one of the disadvantages of the prior art, or to provide a useful alternative. Therefore, developing a method for producing 4-(hydroxymethylphosphinoyl)-2-oxobutanoic acid that may have a high yield, simple purification process, readily available raw materials, and / or environmental friendliness may have important practical significance and / or broad application prospects. SUMMARY

[0007] Provided is a method for producing 4-(hydroxymethylphosphinoyl)-2-oxobutanoic acid, which has a high yield and / or simple operation.

[0008] The present disclosure provides a method for producing 4-(hydroxymethylphosphinoyl)-2-oxobutanoic acid, comprising the steps of: 20

[0009] S1) subjecting a compound of formula I and an oxalate ester of formula II to a Claisen condensation reaction under the action of a basic condensing agent to obtain a metal salt intermediate of formula III;

[0010] S2) exposing the metal salt intermediate of formula III to an aqueous acid to perform neutralization and salt removal, and performing acidolysis to obtain 25 4-(hydroxymethylphosphinoyl)-2-oxobutanoic acid of formula IV; 15 2026237992   22 Sep 2026 OR3

[0011] wherein R1, R2, R3, and R4 are each independently selected from the group consisting of hydrogen and C1 to C5 alkyl, preferably hydrogen and C1 to C4 alkyl, and more preferably hydrogen and C1 to C3 alkyl; and 5

[0012] M+ is an alkali metal cation.

[0013] In some specific embodiments, R1 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, and butyl, preferably methyl or ethyl.

[0014] In some specific embodiments, R2 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, and butyl, preferably methyl or ethyl. 10

[0015] In some specific embodiments, R3 and R4 are independently selected from the group consisting of methyl, ethyl, and propyl, preferably methyl or ethyl.

[0016] M+ is an alkali metal cation, such as Na+, K+, and the like.

[0017] In some specific embodiments, the oxalate ester is selected from the group consisting of dimethyl oxalate, diethyl oxalate, and methyl ethyl oxalate. 15

[0018] Preferably, a molar ratio of the oxalate ester to the compound of formula I is (1.0 to 2.0):1, and more preferably (1.0 to 1.5):1.

[0019] Preferably, the compound of formula I is added to the reaction system by dropwise addition, which facilitates smoother progress of the reaction.

[0020] The basic condensing agent is preferably one or more selected from the group consisting of 20 sodium methoxide, sodium ethoxide, potassium methoxide, potassium ethoxide, potassium hydroxide, sodium hydroxide, a sodium methoxide methanol solution, a sodium ethoxide ethanol solution, a potassium methoxide methanol solution, and a potassium ethoxide ethanol solution.

[0021] Preferably, in the sodium methoxide methanol solution, the sodium ethoxide ethanol solution, the potassium methoxide methanol solution, and the potassium ethoxide ethanol solution, 25 the solute in each solution has a mass content of 10% to 30%, for example, 10%, 20%, or 30%. 2026237992   22 Sep 2026 15

[0022] Preferably, a molar ratio of the basic condensing agent to the compound of formula I is (1.0 to 2.0):1, and more preferably (1.0 to 1.5):1.

[0023] Preferably, the Claisen condensation reaction is performed with one or more solvents selected from the group consisting of benzene, toluene, xylene, chlorobenzene, methanol, and ethanol, and more preferably toluene, benzene, methanol, or ethanol.

[0024] Preferably, the Claisen condensation reaction is performed at a temperature of -40°C to 70°C, more preferably 0°C to 50°C, and further preferably 15°C to 30°C. In some specific embodiments, the Claisen condensation reaction is performed at room temperature.

[0025] Preferably, the Claisen condensation reaction is performed for 5 h to 15 h.

[0026] After the reaction is completed, an aqueous acid is added to the reaction system, so that salts generated in the system are precipitated and removed by filtration.

[0027] The salts are generated by reaction between cations of the basic condensing agent and anions of the aqueous acid. In some specific embodiments, the generated salt is sodium chloride.

[0028] In the present disclosure, an aqueous acid is used for salt removal, so that the particle size of the generated salt is controlled to approximately D90:150, making it easy to be removed by filtration, thereby solving engineering problems such as small particle size of the generated salt and difficulty in filtration in a salt removal process using anhydrous acid, process problems such as side reactions caused by carbonization of organic matter, and defects such as high use cost and high storage and use hazards. 20

[0029] Using an aqueous acid for salt removal can also effectively inhibit side reactions, improving product yield and quality, and achieving a relatively high removal rate of metal salt ion.

[0030] The aqueous acid is preferably an aqueous solution of one or more acids selected from the group consisting of hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid, oxalic acid, acetic acid, and formic acid. 25

[0031] Preferably, in the aqueous acid, water has a mass content of 1% to 80%, more preferably 10% to 70%, and further preferably 10% to 50%. In some specific embodiments, the mass content of water in the aqueous acid is 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, or 80%, or a range value using any of the above values as an upper limit or a lower limit.

[0032] In the present disclosure, the particle size of the salt can be well controlled by controlling 2026237992   22 Sep 2026 the concentration of the acid.

[0033] Preferably, a molar ratio of an acidic compound in the aqueous acid to the compound of formula I is (0.5 to 7.0):1, and more preferably (1.0 to 1.5):1.

[0034] In the present disclosure, the method for removing salts by filtration is not particularly limited, and filtration methods generally applicable in the art may be used, including but not limited to gravity filtration, vacuum filtration, pressure filtration, centrifugal filtration, membrane filtration, and the like.

[0035] The maximum pore size of filter paper is controlled within the range of 3 pm to 300 pm, the mesh count of filter cloth is selected to be 50 to 5000 mesh, and the pore size of a filter membrane is within the range of 3 pm to 300 pm, so as to meet requirements for separation precision and filtration flux of different salts.

[0036] After the salts are removed by filtration, acidolysis is performed on the product to remove the hydroxyl protecting group.

[0037] The acidic compound used for the acidolysis is preferably one or more selected from the group consisting of hydrochloric acid, sulfuric acid, and phosphoric acid, in a form of an aqueous solution.

[0038] Preferably, in the aqueous solution, the acidic compound has a mass content of 10% to 36%, and more preferably 20% to 30%.

[0039] A molar ratio of the acidic compound to the compound of formula I is (0 to 6.0):1, more 20 preferably (1 to 3):1, and further preferably (2 to 3):1.

[0040] Preferably, the acidolysis is performed at a temperature of 80°C to 110°C, and more preferably 85°C to 95°C.

[0041] Preferably, the acidolysis is performed for 1 h to 5 h, and more preferably 2 h to 4 h.

[0042] After acidolysis, the solvent is removed by distillation to obtain 25 4-(hydroxymethylphosphinoyl)-2-oxobutanoic acid. Test    results    show that the 4-(hydroxymethylphosphinoyl)-2-oxobutanoic acid produced by the method of the present disclosure has a purity higher than 95%, a yield higher than 90%, and a metal salt ion removal rate higher than 99%. 15 2026237992   22 Sep 2026

[0043] Compared with the prior art, the present disclosure provides a method for producing 4-(hydroxymethylphosphinoyl)-2-oxobutanoic acid, comprising the steps of: S1) subjecting a compound of formula I and an oxalate ester of formula II to a Claisen condensation reaction under the action of a basic condensing agent to obtain a metal salt intermediate; S2) exposing the metal salt intermediate to an aqueous acid to perform neutralization and salt removal, and performing acidolysis to obtain 4-(hydroxymethylphosphinoyl)-2-oxobutanoic acid of formula IV. In the present disclosure, through an aqueous-acid pre-desalting process, after the Claisen condensation reaction is completed, the cation in the basic condensing agent, for example, a sodium ion, is displaced by adding an aqueous acid, thereby generating a corresponding metal salt. The metal salt is rapidly precipitated in the solvent system, and the particle size of the generated salt is effectively controlled, so that the salt is easy to remove by filtration, and the mother liquor is then subjected to acidic hydrolysis to obtain the product 4-(hydroxymethylphosphinoyl)-2-oxobutanoic acid, which has characteristics such as simple operation and low energy consumption. BRIEF DESCRIPTION OF DRAWINGS

[0044] FIG. 1 is an overlay chromatogram of 4-(hydroxymethylphosphinoyl)-2-oxobutanoic acid and an oxalic acid reference standard. DETAILED DESCRIPTION 20

[0045] The technical solutions of the present disclosure are clearly and completely described below with reference to the examples of the present disclosure. The described examples are merely some, but not all, of the embodiments of the present disclosure. All other embodiments obtained by a person of ordinary skill in the art based on the examples of the present disclosure without creative effort shall fall within the protection scope of the present disclosure. 25

[0046] There is no particular limitation on the sources of all raw materials of the present disclosure, and raw materials purchased on the market or prepared according to conventional methods well known to those skilled in the art may be used. 15 Example 1 2026237992   22 Sep 2026

[0047] 48.2 g of diethyl oxalate (0.33 mol), 150 g of toluene, and 24.5 g of sodium ethoxide (0.36 mol) were sequentially added to a 1000 mL reaction flask. 62.5 g of ethyl 3-(ethoxymethylphosphinoyl)propanoate (0.30 mol) was added dropwise at room temperature over 1 hour, and the reaction was continued at room temperature for 10 hours. Then, 39.5 g of 36% 5 concentrated hydrochloric acid (0.39 mol, water content 64%) was added, and sodium chloride solid precipitated. Vacuum filtration was performed using filter paper having a pore size of 7 pm to 8 pm, and the filter cake was dried (particle size D90:167). 147.9 g of 20% hydrochloric acid was added to the mother liquor, the mixture was heated to 90°C for hydrolysis for 3 hours, and low-boiling components were removed by distillation under reduced pressure to obtain 54.5 g of 0 4-(hydroxymethylphosphinoyl)-2-oxobutanoic acid (purity 95.0%). The calculated yield was 95.8%, and the sodium ion removal rate was 99.6%. Meanwhile, identification showed that the impurity was mainly oxalic acid produced by hydrolysis of excess diethyl oxalate.

[0048] FIG. 1 is an overlay chromatogram of 4-(hydroxymethylphosphinoyl)-2-oxobutanoic acid and an oxalic acid reference standard. The retention time of peak No. 10 closely matches with that 15 of oxalic acid (retention time 14.67 min), indicating that the sample contains an oxalic acid impurity. Examples 2 to 19

[0049] The raw materials and their amounts are shown in Table 1. 4-(hydroxymethylphosphinoyl)-2-oxobutanoic acid was prepared by the same preparation method as 20 that in Example 1.

[0050] Table 1 lists the yields of different examples with different adducts, oxalate esters, bases, and solvents.

[0051] As shown in Table 1, the Claisen condensation reaction was conducted on scales of 0.4 mol and 0.3 mol, respectively, and relevant parameters such as the molar ratios among related 25 materials and reaction duration remained unchanged. Table 1 Example Adduct Oxalate ester Base Solvent Yield / % 2 R1 is ethyl; R2 is ethyl diethyl oxalate sodium methoxide toluene 94.2% 2026237992   22 Sep 2026 3 R1 is ethyl; R2 is ethyl dimethyl oxalate sodium ethoxide toluene 95.1% 4 R1 is ethyl; R2 is ethyl dimethyl oxalate sodium methoxide toluene 95.2% 5 R1 is ethyl; R2 is methyl diethyl oxalate sodium ethoxide toluene 95.4% 6 R1 is ethyl; R2 is methyl diethyl oxalate sodium methoxide toluene 96.3% 7 R1 is ethyl; R2 is methyl dimethyl oxalate sodium ethoxide toluene 95.2% 8 R1 is ethyl; R2 is methyl dimethyl oxalate sodium methoxide toluene 95.5% 9 R1 is ethyl; R2 is ethyl methyl ethyl oxalate sodium ethoxide toluene 95.5% 10 R1 is methyl; R2 is ethyl diethyl oxalate sodium ethoxide toluene 96.1% 11 R1 is ethyl; R2 is ethyl diethyl oxalate potassium methoxide toluene 94.2% 12 R1 is ethyl; R2 is ethyl diethyl oxalate potassium ethoxide toluene 96.1% 13 R1 is ethyl; R2 is ethyl diethyl oxalate potassium hydroxide toluene 95.3% 14 R1 is ethyl; R2 is ethyl diethyl oxalate 30% sodium methoxide methanol solution toluene 95.3% 15 R1 is ethyl; R2 is methyl diethyl oxalate potassium methoxide toluene 93.0% 16 R1 is ethyl; R2 is methyl dimethyl oxalate potassium methoxide toluene 95.0% 17 R1 is ethyl; R2 is ethyl diethyl oxalate sodium ethoxide benzene 94.2% 18 R1 is ethyl; R2 is ethyl diethyl oxalate sodium ethoxide methanol 90.2% 19 R1 is ethyl; R2 is ethyl diethyl oxalate sodium ethoxide ethanol 91.2% 2026237992   22 Sep 2026 Examples 20 to 33

[0052] The raw materials and their amounts are shown in Table 2. 4-(hydroxymethylphosphinoyl)-2-oxobutanoic acid was prepared by the same preparation method as that in Example 1. 5

[0053] Table 2 lists the yields, salt particle sizes, and sodium ion removal rates of different examples using different aqueous acids. The Claisen condensation reaction was conducted on a scale of 0.3 mol, and, except that the respective molar ratios of sulfuric acid and oxalic acid were reduced by half, other relevant parameters such as the molar ratios among related materials and reaction duration remained unchanged. Table 2 Example Acid Water content Yield Particle size D90 Sodium ion removal rate 20 hydrochloric acid 70% 96.3% 170 99.5% 21 hydrochloric acid 80% 95.3% 161 99.2% 22 hydrochloric acid 90% 95.0% 165 76.2% 23 sulfuric acid 20% 95.1% 156 99.6% 24 sulfuric acid 50% 95.4% 160 99.6% 25 sulfuric acid 70% 94.1% 155 99.5% 26 sulfuric acid 90% 94.2% 149 54.5% 27 phosphoric acid 20% 95.6% 169 99.7% 28 phosphoric acid 50% 95.1% 170 99.5% 29 phosphoric acid 90% 95.2% 156 20.5% 30 nitric acid 30% 95.9% 156 99.5% 31 oxalic acid 10% 93.5% 174 99.6% 32 acetic acid 10% 93.9% 173 99.6% 33 formic acid 15% 93.9% 164 99.6%

[0054] When the water content of the aqueous acid was higher than 90%, the sodium ion removal rate was greatly reduced; when the water content was lower than 70%, the salt removal effect was relatively ideal and was not less than 95%. 2026237992   22 Sep 2026 15 Example 34

[0055] With reference to Example 1, the Claisen condensation reaction was conducted on a scale of 0.3 mol. During the salt removal process, 146 g of a 30% aqueous hydrochloric acid solution was directly added, the salt was removed by filtration, and then the mixture was heated for hydrolysis. Other processes and relevant parameters such as the molar ratios among related materials and reaction duration remained unchanged. 53.6 g of 4-(hydroxymethylphosphinoyl)-2-oxobutanoic acid (purity 96.5%) was obtained. The calculated yield was 95.8%, and the sodium ion removal rate was 99.5%. Example 35

[0056] With reference to Example 1, the Claisen condensation reaction was conducted on a scale of 0.3 mol. After salt removal with concentrated hydrochloric acid, 150 g of 2% dilute sulfuric acid was added to the mother liquor for hydrolysis. Other processes and relevant parameters such as the molar ratios among related materials and reaction duration remained unchanged. 60.1 g of 4-(hydroxymethylphosphinoyl)-2-oxobutanoic acid (purity 85.1%) was obtained. The calculated yield was 94.6%, and the sodium ion removal rate was 99.5%. Example 36 20

[0057] With reference to Example 1, the Claisen condensation reaction was conducted on a scale of 0.3 mol. After salt removal using sulfuric acid having a water content of 30%, 150 g of water was directly added to the mother liquor, and then the mixture was heated for hydrolysis. Other processes and relevant parameters such as the molar ratios among related materials and reaction duration remained unchanged. 61.2 g of 4-(hydroxymethylphosphinoyl)-2-oxobutanoic acid (purity 84.1%) 25 was obtained. The calculated yield was 95.3%, and the sodium ion removal rate was 99.6%. Example 37

[0058] With reference to Example 1, the Claisen condensation reaction was conducted on a scale 2026237992   22 Sep 2026 15 of 0.3 mol, and salt removal was performed with concentrated hydrochloric acid. After 20% hydrochloric acid was added to the mother liquor, phase separation was performed, and the aqueous phase was heated for hydrolysis. Other processes and relevant parameters such as the molar ratios among related materials and reaction duration remained unchanged. 53.3 g of 4-(hydroxymethylphosphinoyl)-2-oxobutanoic acid (purity 96.1%) was obtained. The calculated yield was 94.8%, and the sodium ion removal rate was 99.6%. Example 38

[0059] With reference to Example 1, the Claisen condensation reaction was conducted on a scale of 0.3 mol. After salt removal with concentrated hydrochloric acid, 2000-mesh filter cloth was used for vacuum filtration, acid was added to the mother liquor for hydrolysis, and the solvent was removed. 54.4 g of 4-(hydroxymethylphosphinoyl)-2-oxobutanoic acid (purity 94.9%) was obtained. The calculated yield was 95.5%, and the sodium ion removal rate was 99.6%. Example 39

[0060] With reference to Example 1, the Claisen condensation reaction was conducted on a scale of 0.3 mol. After salt removal with concentrated hydrochloric acid, a filter membrane having a pore size of 7 pm to 8 pm was used for vacuum filtration, acid was added to the mother liquor for hydrolysis, and the solvent was removed. 54.8 g of 4-(hydroxymethylphosphinoyl)-2-oxobutanoic 20 acid (purity 94.0%) was obtained. The calculated yield was 95.3%, and the sodium ion removal rate was 99.6%. Comparative Example 1

[0061] 48.2 g of diethyl oxalate (0.33 mol), 150 g of toluene, and 24.5 g of sodium ethoxide (0.36 25 mol) were sequentially added to a 1000 mL reaction flask. 62.5 g of ethyl 3-(ethoxymethylphosphinoyl)propanoate (0.30 mol) was added dropwise at room temperature over 1 hour, and the reaction was continued at room temperature for 10 hours. Then, 14.2 g of hydrogen chloride gas (0.39 mol) was introduced, and sodium chloride solid precipitated. Vacuum filtration was performed using filter paper having a pore size of 7 pm to 8 pm, and the filter cake was dried 2026237992   22 Sep 2026 (particle size D90:33). The filtration was difficult and the filtration duration was significantly prolonged. 147.9 g of 20% hydrochloric acid was added to the mother liquor, the mixture was heated to 90°C for hydrolysis for 3 hours, and low-boiling components were removed by distillation under reduced pressure. 52.5 g of 4-(hydroxymethylphosphinoyl)-2-oxobutanoic acid (purity 94.6%) was 5 obtained. The calculated yield was 91.9%, and the sodium ion removal rate was 99.5%.

[0062] The above examples are merely provided to facilitate understanding of the method and core concept of the present disclosure. It should be noted that, for a person of ordinary skill in the art, several improvements and modifications may be made to the present disclosure without departing from the principles of the present disclosure, and these improvements and modifications also fall within the protection scope of the claims of the present disclosure.

Claims

1. A method for producing 4-(hydroxymethylphosphinoyl)-2-oxobutanoic acid, comprising the steps of:S1) subjecting a compound of formula I and an oxalate ester of formula II to a Claisen condensation reaction under the action of a basic condensing agent to obtain a metal salt intermediate of formula III;S2) exposing the metal salt intermediate of formula III to an aqueous acid to performneutralization and salt removal, and performing acidolysis to obtain4-(hydroxymethylphosphinoyl)-2-oxobutanoic acid of formula IV;wherein R1, R2, R3, and R4 are each independently selected from the group consisting ofhydrogen and C1 to C5 alkyl; andM+ is an alkali metal cation.

152. The method according to claim 1, wherein R1 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, and butyl;R2 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, and butyl; andR3 and R4 are each independently selected from the group consisting of methyl, ethyl, and 20 propyl.

3. The method according to claim 1 or claim 2, wherein the basic condensing agent is one or more selected from the group consisting of sodium methoxide, sodium ethoxide, potassium methoxide, potassium ethoxide, potassium hydroxide, sodium hydroxide, a sodium methoxide 25 methanol solution, a sodium ethoxide ethanol solution, a potassium methoxide methanol solution,2026237992   22 Sep 2026and a potassium ethoxide ethanol solution; andin the sodium methoxide methanol solution, the sodium ethoxide ethanol solution, the potassium methoxide methanol solution, and the potassium ethoxide ethanol solution, the solute in each solution has a mass content of 10% to 30%.

4. The method according to any one of claims 1 to 3, wherein a molar ratio of the basic condensing agent to the compound of formula I is (1.0 to 2.0):1.

5. The method according to any one of claims 1 to 4, wherein the Claisen condensation reaction is performed with one or more solvents selected from the group consisting of benzene, toluene, xylene, chlorobenzene, methanol, and ethanol; andthe Claisen condensation reaction is performed at a temperature of -40°C to 70°C.

6. The method according to any one of claims 1 to 5, wherein a molar ratio of the oxalate ester to the compound of formula I is (1.0 to 2.0):1.

7. The method according to any one of claims 1 to 6, wherein the aqueous acid is an aqueous solution of one or more acids selected from the group consisting of hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid, oxalic acid, acetic acid, and formic acid; and20 in the aqueous acid, water has a mass content of 1% to 80%.

8. The method according to any one of claims 1 to 7, wherein a molar ratio of an acidic compound in the aqueous acid to the compound of formula I is (0.5 to 7.0):1.25        9. The method according to any one of claims 1 to 8, wherein an acidic compound is used forthe acidolysis, and the acidic compound is one or more selected from the group consisting of hydrochloric acid, sulfuric acid, and phosphoric acid, in a form of an aqueous solution;in the aqueous solution, the acidic compound has a mass content of 10% to 36%; and152026237992   22 Sep 2026a molar ratio of the acidic compound to the compound of formula I is (0 to 6.0):1.

10. The method according to any one of claims 1 to 9, wherein the acidolysis is performed at a temperature of 80°C to 110°C.

511. The 4-(hydroxymethylphosphinoyl)-2-oxobutanoic acid obtained by the method of any one of claims 1 to 10.

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