Method for preparing glufosinate

Abstract

A method for preparing glufosinate ammonium or a salt thereof, or a mixture of enantiomers thereof, in any ratio, comprising reacting a compound of formula (II) or a salt thereof, or an enantiomer thereof, or a mixture of enantiomers thereof, in any ratio, with one or more compounds of formula (III) or a mixture thereof. TIFF2022551341000032.tif24149

Description

Detailed Description of the Invention

[0001] [Technical field] The present invention relates to a method for preparing glufosinate.

[0002] [Prior Art] Glufosinate is an important herbicide.

[0003] [Contents of the invention] The present invention relates to a process for preparing glufosinate of formula (I) or a salt thereof, its enantiomer or a mixture of its enantiomers in all ratios, the process comprising: [ka] a) a compound of formula (II) or a salt thereof, an enantiomer thereof or a mixture of enantiomers in all ratios, [ka] with one or more compounds or mixtures of formula (III), the mixture is a mixture comprising one or more compounds of formula (IV) and one or more compounds of formula (V); or a mixture comprising one or more compounds of formula (IV) and one or more compounds of formula (III); or a mixture comprising one or more compounds of formula (V) and one or more compounds of formula (III); or a mixture comprising one or more compounds of formula (III), one or more compounds of formula (IV) and one or more compounds of formula (V); [ka] b) reacting the intermediate, whether isolated or not, in the presence of water and an acid or a base to obtain glufosinate (I) or a salt thereof, an enantiomer or a mixture of enantiomers thereof in all ratios; When PG is an amino protecting group, the method can further include removing the amino protecting group; Here, Hal1 and Hal 2 are each independently halogen; PG is hydrogen or an amino protecting group; R1, R2, R3 and R4 are each independently alkyl, phenyl or substituted phenyl, and when the mixture comprises a mixture of one or more compounds of formula (IV) and one or more compounds of formula (III), or when the mixture comprises a mixture of one or more compounds of formula (III), one or more compounds of formula (IV) and one or more compounds of formula (V), R2 is either R3 or R4; and the chiral carbon atom is labeled with *.

[0004] The present invention further relates to a process for preparing enantiomerically pure glufosinate of formula (I) or a salt thereof, the process comprising: [ka] a1) an enantiomerically pure compound of formula (II) or a salt thereof, [ka] A compound of formula (III), [ka] or one or more compounds or mixtures of formula (III), the mixture is a mixture comprising one or more compounds of formula (IV) and one or more compounds of formula (V); or a mixture comprising one or more compounds of formula (IV) and one or more compounds of formula (III); or a mixture comprising one or more compounds of formula (V) and one or more compounds of formula (III); or a mixture comprising one or more compounds of formula (III), one or more compounds of formula (IV) and one or more compounds of formula (V); [ka] b1) reacting the intermediate, whether isolated or not, in the presence of water and an acid or a base to obtain enantiomerically pure glufosinate (I) or a salt thereof; Equipped with When PG is an amino protecting group, the method can further include removing the amino protecting group; Here, Hal 1 and Hal 2 are each independently halogen; PG is hydrogen or an amino protecting group; R1, R2, R3 and R4 are each independently alkyl, phenyl or substituted phenyl, and when the mixture comprises a mixture of one or more compounds of formula (IV) and one or more compounds of formula (III), or when the mixture comprises a mixture of one or more compounds of formula (III) and one or more compounds of formula (IV) and one or more compounds of formula (V), R2 is either R3 or R4; and the chiral carbon atom is labeled with *.

[0005] In certain embodiments, one compound of formula (III) is used, for example, chloro(ethoxy)(methyl)phosphane.

[0006] In certain embodiments, a mixture of one compound of formula (IV) and one compound of formula (V) is used, such as a mixture of dichloro(methyl)phosphane and diethylmethylphosphonite, to which a compound of formula (III), e.g., chloro(ethoxy)(methyl)phosphane, can be further added in any ratio.

[0007] Further, the enantiomeric ratio, as the (L):(D)-enantiomers or (D):(L)-enantiomers, is 50.5:49.5 to 99.5:0.5.

[0008] Furthermore, the enantiomeric ratio, as the (L):(D)-enantiomers, is 50.5:49.5 to 99.5:0.5.

[0009] Furthermore, PG is hydrogen.

[0010] Also, Hal 1 is a chlorine atom.

[0011] Also, Hal 2 is a chlorine atom.

[0012] Furthermore, R1, R2, R3 and R4 are each independently C1 to C6 alkyl, preferably C1 to C4 alkyl.

[0013] Additionally, R1 is ethyl.

[0014] Additionally, R2 is ethyl.

[0015] Additionally, R3 is ethyl.

[0016] Additionally, R4 is ethyl.

[0017] In certain embodiments, the mixture is a mixture of one or more compounds of formula (IV) and one or more compounds of formula (III), wherein the molar ratio of the compounds of formula (IV) to the compounds of formula (III) is (0.9-1.1):1 or (0.05-1.1):1; or the mixture is a mixture of one or more compounds of formula (V) and one or more compounds of formula (III), wherein the molar ratio of the compounds of formula (V) to the compounds of formula (III) is (0.9-1.1):1 or (0.05-1.1):1; or the mixture is a mixture comprising one or more compounds of formula (IV) and one or more compounds of formula (V), wherein the molar ratio of the compounds of formula (IV) to the compounds of formula (V) is (0.9-1.1):1.

[0018] In the above step a) or a1), the reaction can proceed at room temperature, and the reaction temperature can be 20 to 200° C., preferably 90 to 140° C., taking into consideration the reaction efficiency.

[0019] The above step a) or a1) is carried out in the presence of a base.

[0020] Furthermore, the base in the above step a) or a1) is an organic base or ammonia.

[0021] Further, in the above step a) or a1), the organic base is selected from the group consisting of organic amines, pyridine derivatives having 1 to 3 substituents bonded to one or more carbon atoms in pyridine or a heterocycle, and piperidine derivatives having 1 to 3 substituents bonded to one or more carbon atoms in piperidine or a heterocycle.

[0022] Additionally, the organic base is selected from the group consisting of triethylamine, piperidine or pyridine.

[0023] Furthermore, in the above step a) or a1), the molar ratio of the base to the total amount of the compound of formula (III) and the compound of formula (V) is (1-10):1.

[0024] Furthermore, in the above step a) or a1), the reaction is carried out under solvent-free conditions or in an inert solvent.

[0025] Further, in the above step a) or a1), the inert solvent is selected from any one or more of benzene solvents, amide solvents, hydrocarbon solvents, halogenated hydrocarbon solvents, sulfone or sulfoxide solvents, ether solvents or ester solvents; preferably, the inert solvent is selected from any one or more of benzene-based solvents, amide-based solvents, halogenated hydrocarbon-based solvents, ether-based solvents or ester-based solvents.

[0026] Further, in the above step a) or a1), the inert solvent is selected from one or more of chlorobenzene, trimethylbenzene, 1,4-dioxane, 1,2-dichloroethane, dimethylsulfoxide, N-methylpyrrolidone, N,N-dimethylformamide, petroleum ether, n-heptane, tetrahydrofuran, methyltetrahydrofuran, benzene, toluene, ethyl acetate, and butyl acetate.

[0027] Further, in the above step a) or a1), the molar ratio of the compound or mixture of formula (III) to the compound of formula (II) is 1:(0.8-10), preferably 1:(1-3); or the molar ratio of the compound of formula (II) to the compound or mixture of formula (III) is 1:(0.8-10), preferably 1:(1-3).

[0028] In the above step b) or b1), an inorganic acid or an organic acid is added.

[0029] Also, the inorganic acid is hydrochloric acid or sulfuric acid.

[0030] In the above step b) or b1), the base is an inorganic base or an organic base.

[0031] Further, the base is an alkali metal hydroxide, an alkaline earth metal hydroxide, an alkali metal carbonate, an alkaline earth metal carbonate, an alkali metal bicarbonate or an alkaline earth metal bicarbonate.

[0032] Further, the base is NaOH, KOH or Ba(OH)2.

[0033] Furthermore, in the above step b) or b1), the reaction temperature is 20 to 150°C.

[0034] In a particular embodiment, a compound of formula (IIa) is reacted with a compound of formula (IIIa): [ka] An acid (eg, hydrochloric acid) is then added to obtain L-glufosinate.

[0035] The present invention further provides a compound of formula (III). [ka] During the ceremony, Hal 2 and R2 is as defined above.

[0036] The present invention further provides the use of a compound of formula (III), in particular a compound of formula (IIIa), in the preparation of glufosinate or a salt thereof, or L-glufosinate or a salt thereof. [ka]

[0037] The present invention further provides a mixture comprising one or more compounds of formula (IV) and one or more compounds of formula (V); or a mixture comprising one or more compounds of formula (IV) and one or more compounds of formula (III); or a mixture comprising one or more compounds of formula (V) and one or more compounds of formula (III); or a mixture comprising one or more compounds of formula (III), one or more compounds of formula (IV) and one or more compounds of formula (V). [ka] During the ceremony, Hal 2 , R2, R3 and R4 are as defined above.

[0038] Further, the mixture is a mixture containing one or more compounds of formula (IV) and one or more compounds of formula (V), wherein the molar ratio of the compounds of formula (IV) to the compounds of formula (V) is (0.9-1.1):1; or the mixture is a mixture containing one or more compounds of formula (IV) and one or more compounds of formula (III), wherein the molar ratio of the compounds of formula (IV) to the compounds of formula (III) is (0.9-1.1):1 or (0.05-1.1):1; or the mixture is a mixture containing one or more compounds of formula (V) and one or more compounds of formula (III), wherein the molar ratio of the compounds of formula (V) to the compounds of formula (III) is (0.9-1.1):1 or (0.05-1.1):1.

[0039] Furthermore, the compound of formula (IV) is diethylmethylphosphonite and the compound of formula (V) is dichloro(methyl)phosphane.

[0040] The present invention further provides the use of the above mixture in the preparation of glufosinate or a salt thereof, or L-glufosinate or a salt thereof.

[0041] The method of the present invention is particularly suitable for preparing glufosinate, and substantially reduces the steps of existing preparation processes. In particular, in the preparation of L-glufosinate, the product can effectively maintain the ee value of the raw material. For example, when an enantiomerically pure raw material (e.g., the enantiomeric excess (% ee) is more than 90%) is used, the enantiomeric excess (% ee) of the prepared L-glufosinate is, for example, more than 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95%.

[0042] Unless otherwise stated, terms used in the specification and claims have the following meanings:

[0043] The term "amino protecting group" refers to a group that can be attached to the nitrogen atom in an amino group to protect the amino group from participating in a reaction and can be easily removed in a subsequent reaction. Suitable amino protecting groups include, but are not limited to, the following protecting groups: Carbamate groups of the formula -C(O)OR, where R is methyl, ethyl, tert-butyl, benzyl, phenethyl, CH2=CH-CH2-, etc.; amide groups of the formula -C(O)-R', where R' is methyl, ethyl, phenyl, trifluoromethyl, etc.; N-sulfonyl derivative groups of the formula -SO2-R" where R" is tolyl, phenyl, trifluoromethyl, 2,2,5,7,8-pentamethylchroman-6-yl-, 2,3,6-trimethyl-4-methoxybenzene, etc.

[0044] The term "alkyl" refers to saturated aliphatic hydrocarbon groups, including straight and branched chain groups, having 1 to 18 carbon atoms. Preferred are alkyls having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, 2-propyl, n-butyl, isobutyl, tert-butyl, and pentyl. The alkyl may be substituted or unsubstituted, and if substituted, the substituents may be halogen, nitro, sulfonyl, etheroxy, etherthio, ester, thioester, or cyano.

[0045] C1-C4 alkyl is a straight or branched chain containing saturated hydrocarbon chain having 1 to 4 carbon atoms. It can be methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl or tert-butyl.

[0046] As used herein, "a mixture of enantiomers in all ratios" has the same meaning as "a mixture of enantiomers in any ratio."

[0047] [Mode for carrying out the invention] [Preparation of Compound 1] [ka] 10 g of L-homoserine lactone hydrochloride (ee value 99%, 137.56 g / mol, 0.073 mol) was weighed into a reaction flask and 50 mL of ethanol (46.07 g / mol, 0.886 mol, 0.816 g / mL) was added (the molar ratio of homoserine lactone hydrochloride to ethanol is 1:12.1). The system was cooled to 10°C and 21.7 g of thionyl chloride (118.97 g / mol, 0.182 mol) was slowly added dropwise (the molar ratio of L-homoserine lactone hydrochloride to thionyl chloride is 1:2.5). The temperature of the system was maintained at 10°C and stirred for 30 minutes. The reaction was heated to 35°C and stirred for 20 hours, during which air bubbles were continuously generated. The reaction was monitored by LC-MS. The reaction was stopped, the system was cooled to room temperature, and the remaining thionyl chloride and ethanol were distilled off under reduced pressure. The solid residue was slurried with 30 mL of n-hexane / ethyl acetate mixed solvent (the volume ratio of n-hexane to ethyl acetate is 2:1), filtered, and dried to obtain 13.69 g of chloro-homoserine ethyl ester hydrochloride (202.08 g / mol, 0.0657 mol), where the HPLC purity is 97% and the calculated yield based on the amount of reactant L-homoserine lactone hydrochloride is 90%.

[0048] The chloro-homoserine ethyl ester hydrochloride solid was reacted with saturated sodium carbonate solution. The system was adjusted to pH 7-8 and extracted with ethyl acetate three times. The amount of ethyl acetate in the three extraction processes was 30mL, 10mL and 10mL, respectively. The organic phase was collected and concentrated to obtain 10.30g of oily target product chloro-homoserine ethyl ester (165.62g / mol, 0.0591mol), where the HPLC purity was 95%, the ee value was 99%, and the calculated yield based on the intermediate product chloro-homoserine ethyl ester hydrochloride was 90%. MS (ESI): m / z [M + H] + calculated for C6H13ClNO2: 166.06, found: 166.0. 1H NMR(CDCl3, 400 MHz) δ: 4.04 (q, J =7.1 Hz, 2H), 3.65 - 3.50 (m, 2H),3.48 (dd, J =9.0, 4.7 Hz, 1H), 2.05 (dddd, J =14.7, 8.5, 6.4, 4.6 Hz, 1H), 1.87- 1.64 (m, 3H), 1.13 (t, J =7.2 Hz, 3H). 13 C NMR(CDCl3, 100 MHz) δ: 175.3, 61.0, 51.6, 41.5, 37.0, 14.1.

[0049] Example 1 [ka] Under a nitrogen atmosphere, diethyl methylphosphonite (65.9 g, 484.8 mmol, 1.0 eq) and 1,4-dioxane (66 g) were added to a round-bottom flask, and a solution of dichloro(methyl)phosphane (62.3 g, 533.3 mmol, 1.1 eq) in 1,4-dioxane (63 g) was added dropwise using a constant pressure funnel and stirred at room temperature overnight. 1,4-dioxane and chloro(ethoxy)(methyl)phosphane (colorless liquid, 85.8 g, yield: 70%) were distilled off under reduced pressure. 1 H NMR(D2O, 43 MHz) δ: 3.92 - 2.96 (m, 2H), 1.31 (d, J =12.8 Hz, 3H), 0.84(t, J =7.0 Hz, 3H).

[0050] Example 2 [ka] Compound 1 (40.0 g, 242.4 mmol, 1.0 eq), chlorobenzene (81.9 g, 727.2 mmol, 3.0 eq), triethylamine (29.4 g, 290.9 mmol, 1.2 eq) were added to a three-neck flask under nitrogen atmosphere, and chloro(ethoxy)(methyl)phosphane (36.8 g, 290.9 mmol, 1.2 eq) was added dropwise and stirred at room temperature for 2 hours. The reaction was heated to 100 °C and allowed to proceed for 20 hours. MS detection showed that the starting material had disappeared. The reaction was cooled to room temperature, 36% HCl (294.9 mL, 3432.6 mmol, 14.0 equiv.) was added dropwise and heated to reflux until the starting material had completely reacted. The solvent was evaporated, 95% ethanol (200 mL) and water (20 mL) were added, and the mixture was heated to reflux until the product was completely dissolved. The mixture was cooled, crystallized, filtered and dried to give L-glufosinate (white crystals, 38.4 g, yield: 88%, 98% ee). MS (ESI): m / z [M + H] + calculated for C5H13NO4P: 182.05, found 182.1. 1 H NMR(D2O, 400 MHz) δ: 4.08 (t, J =6.2 Hz, 1H), 2.11 (dddd, J =14.6,11.0, 8.7, 6.0 Hz, 2H), 1.99 - 1.73 (m, 2H), 1.44 (d, J =14.2 Hz, 3H). 13 C NMR(D2O, 100 MHz) δ: 171.0, 52.8, 52.6, 25.5, 24.6, 22.6, 22.5, 13.9,13.0. 31 P NMR(DO, 160 MHz) δ: 53.8.

[0051] Example 3 [ka] Compound 1 (40.0 g, 242.4 mmol, 1.0 eq), chlorobenzene (81.9 g, 727.2 mmol, 3.0 eq), pyridine (23.0 g, 290.9 mmol, 1.2 eq) were added to a three-neck flask under nitrogen atmosphere, and chloro(ethoxy)(methyl)phosphane (36.8 g, 290.9 mmol, 1.2 eq) was added dropwise and stirred at room temperature for 2 hours. The reaction was heated to 100 °C and allowed to proceed for 20 hours. MS detection showed that the starting material had disappeared. The reaction was cooled to room temperature and 36% HCl (294.9 mL, 3432.6 mmol, 14.0 equiv.) was added dropwise and heated to reflux until the starting material had completely reacted. The solvent was evaporated, 95% ethanol (200 mL) and water (20 mL) were added, and the mixture was heated to reflux until the product was completely dissolved. The mixture was cooled, allowed to crystallize, filtered and dried to give L-glufosinate (white crystals, 35.3 g, yield: 81%, 96% ee).

[0052] Example 4 [ka] Compound 1 (40.0 g, 242.4 mmol, 1.0 eq), chlorobenzene (81.9 g, 727.2 mmol, 3.0 eq) and piperidine (24.8 g, 290.9 mmol, 1.2 eq) were added to a three-neck flask under nitrogen atmosphere, and chloro(ethoxy)(methyl)phosphane (36.8 g, 290.9 mmol, 1.2 eq) was added dropwise and stirred at room temperature for 2 hours. The reaction was heated to 100 °C and allowed to proceed for 20 hours. MS detection showed that the starting material had disappeared. The reaction was cooled to room temperature and 36% HCl (294.9 mL, 3432.6 mmol, 14.0 equiv.) was added dropwise and heated to reflux until the starting material had completely reacted. The solvent was evaporated, 95% ethanol (200 mL) and water (20 mL) were added, and the mixture was heated to reflux until the product was completely dissolved. The mixture was cooled, allowed to crystallize, filtered and dried to give L-glufosinate (white crystals, 33.2 g, yield: 76%, 94% ee).

[0053] Example 5 [ka] Compound 1 (40.0 g, 242.4 mmol, 1.0 eq) and chlorobenzene (81.9 g, 727.2 mmol, 3.0 eq) were placed in a three-neck flask under nitrogen. Chloro(ethoxy)(methyl)phosphane (36.8 g, 290.9 mmol, 1.2 eq) was added dropwise while simultaneously bubbling ammonia until saturated. The reaction was stirred at room temperature for 2 h. The reaction was heated to 100 °C and allowed to proceed for 20 h. MS detection showed the disappearance of starting material. The reaction was cooled to room temperature and 36% HCl (294.9 mL, 3432.6 mmol, 14.0 eq) was added dropwise and heated to reflux until the starting material was completely reacted. The solvent was evaporated, 95% ethanol (200 mL) and water (20 mL) were added, and the mixture was heated to reflux until the product was completely dissolved. The mixture was cooled, allowed to crystallize, filtered and dried to give L-glufosinate (white crystals, 38 g, yield: 87%, 97% ee).

[0054] Example 6 [ka] Compound 1 (40.0 g, 242.4 mmol, 1.0 eq), 1,4-dioxane (64 g, 727.2 mmol, 3.0 eq) and triethylamine (29.4 g, 290.9 mmol, 1.2 eq) were added to a three-neck flask under nitrogen atmosphere, and chloro(ethoxy)(methyl)phosphane (36.8 g, 290.9 mmol, 1.2 eq) was added dropwise and stirred at room temperature for 2 hours. The reaction was heated to 100 °C and allowed to proceed for 20 hours. MS detection showed that the starting material had disappeared. The reaction was cooled to room temperature and 36% HCl (294.9 mL, 3432.6 mmol, 14.0 equiv.) was added dropwise and heated to reflux until the starting material had completely reacted. The solvent was evaporated, 95% ethanol (200 mL) and water (20 mL) were added, and the mixture was heated to reflux until the product was completely dissolved. The mixture was cooled, allowed to crystallize, filtered and dried to give L-glufosinate (white crystals, 36.2 g, yield: 83%, 97% ee).

[0055] Example 7 [ka] Dichloro(methyl)phosphane (520.5 mmol, 0.6 eq, purity 90%) was placed in a round-bottom flask at room temperature (20 °C) under nitrogen atmosphere, and diethylmethylphosphonite (1735 mmol, 2.0 eq, purity 98%) was added dropwise using a constant pressure funnel, followed by stirring for 10 min. A solution of compound 1 (867.5 mmol, 1.0 eq, purity 96%, ee value 99%) and triethylamine (107.5 g, 1041 mmol, 1.2 eq, purity 98%) in 1,4-dioxane (500 g) was added dropwise, and stirring was continued for 1.5 h after the addition. The reaction solution was then heated to 90 °C and allowed to proceed for 20 h. The reaction solution was cooled to room temperature, suction filtered, the filter cake was washed with 1,4-dioxane (150 mL × 3), and the filtrate was rotary evaporated to remove 1,4-dioxane. The reaction was added with 100 mL of concentrated hydrochloric acid (36%), heated to 90°C, and allowed to proceed for 10 hours. The solvent was rotary evaporated to dryness, replenished with 200 mL of concentrated hydrochloric acid (36%), and the reaction was continued at 90°C for 10 hours. MS detection showed that the intermediate had disappeared, and analysis of the reaction solution at this point showed that the enantiomeric excess (%ee) of L-glufosinate in the reaction solution was 92%. The reaction solution was cooled to room temperature, rotary evaporated to remove the solvent, 95% ethanol (300 mL) was added, and heated to reflux until the crude product was completely dissolved. The mixture was cooled, crystallized, filtered, and dried to obtain the compound L-glufosinate (yield: 69%, 97%ee).

[0056] In addition to those described herein, various modifications to the present invention will be apparent to those skilled in the art according to the above description. Such modifications are intended to be within the scope of the appended claims. Each reference cited in this specification (including all patents, patent applications, academic papers, books, and any other disclosures) is incorporated herein by reference in its entirety.

Claims

1. A process for preparing glufosinate of formula (I) or a salt thereof, its enantiomer or a mixture of enantiomers in all ratios, the process comprising: 【Chemistry 1】 a) a compound of formula (II) or a salt thereof, its enantiomer or a mixture of its enantiomers in all ratios, 【Chemistry 2】 with a phosphorus-containing compound or mixture selected from one or more compounds of formula (III); or a mixture comprising one or more compounds of formula (IV) and one or more compounds of formula (V); or a mixture comprising one or more compounds of formula (IV) and one or more compounds of formula (III); or a mixture comprising one or more compounds of formula (V) and one or more compounds of formula (III); or a mixture comprising one or more compounds of formula (III), one or more compounds of formula (IV) and one or more compounds of formula (V); 【Chemistry 3】 b) reacting the product obtained in step a), whether it is isolated or not, in the presence of water and an acid or a base to obtain glufosinate (I) or a salt thereof, an enantiomer thereof or a mixture of enantiomers in all ratios; Equipped with When PG is an amino protecting group, the method may further comprise the step of removing the amino protecting group; Here, Hal １ and Hal ２ are each independently a halogen; PG is hydrogen or an amino protecting group; and R １ , R ２ , R ３ and R ４ are each independently alkyl or phenyl, and when the phosphorus-containing mixture comprises a mixture of one or more compounds of formula (IV) and one or more compounds of formula (III), or when the phosphorus-containing mixture comprises a mixture of one or more compounds of formula (III), one or more compounds of formula (IV), and one or more compounds of formula (V), R ２ is R ３ Or R ４ A method, which is either

2. A process for preparing enantiomerically pure glufosinate of formula (I) or a salt thereof, the process comprising: 【Chemistry 4】 a1) reacting an enantiomerically pure compound of formula (II) or a salt thereof with 【Chemistry 5】 with a phosphorus-containing compound or mixture selected from one or more compounds of formula (III); or a mixture comprising one or more compounds of formula (IV) and one or more compounds of formula (V); or a mixture comprising one or more compounds of formula (IV) and one or more compounds of formula (III); or a mixture comprising one or more compounds of formula (V) and one or more compounds of formula (III); or a mixture comprising one or more compounds of formula (III), one or more compounds of formula (IV) and one or more compounds of formula (V); 【Chemistry 6】 b1) reacting the product obtained in step a1), whether it is isolated or not, in the presence of water and an acid or a base to obtain enantiomerically pure glufosinate (I) or a salt thereof; Equipped with When PG is an amino protecting group, the method may further comprise the step of removing the amino protecting group; Here, Hal １ and Hal ２ are each independently a halogen; PG is hydrogen or an amino protecting group; and R １ , R ２ , R ３ and R ４ are each independently alkyl or phenyl, and when the phosphorus-containing mixture comprises a mixture of one or more compounds of formula (IV) and one or more compounds of formula (III), or when the phosphorus-containing mixture comprises a mixture of one or more compounds of formula (III), one or more compounds of formula (IV), and one or more compounds of formula (V), R ２ is R ３ Or R ４ A method, which is either

3. The method according to claim 1, characterized in that the enantiomeric ratio of the glufosinate of formula (I) is from 50.5:49.5 to 99.5:0.5 as (L):(D)-enantiomers or (D):(L)-enantiomers.

4. The method according to claim 3, characterized in that the enantiomeric ratio of the glufosinate of formula (I) is from 50.5:49.5 to 99.5:0.5 as (L):(D)-enantiomers.

5. The process according to any one of claims 1 to 4, characterized in that PG is hydrogen.

6. Hal １ The method according to any one of claims 1 to 4, characterized in that is a chlorine atom.

7. Hal ２ The method according to any one of claims 1 to 4, characterized in that is a chlorine atom.

8. R １ , R ２ , R ３ and R ４ Each of them is independently C １ ~C ６ The method according to any one of claims 1 to 4, characterized in that it is alkyl.

9. R １ , R ２ , R ３ and R ４ Each of them is independently C １ ~C ４ 9. The method of claim 8, wherein the alkyl group is an alkyl group.

10. R １ The process according to any one of claims 1 to 4, characterized in that is ethyl.

11. R ２ The process according to any one of claims 1 to 4, characterized in that is ethyl.

12. R ３ The process according to any one of claims 1 to 4, characterized in that is ethyl.

13. R ４ The process according to any one of claims 1 to 4, characterized in that is ethyl.

14. 5. The method of any one of claims 1 to 4, wherein the phosphorus-containing mixture is a mixture of one or more compounds of formula (IV) and one or more compounds of formula (III), wherein the molar ratio of the compounds of formula (IV) to the compounds of formula (III) is (0.05-1.1):1; or the phosphorus-containing mixture is a mixture of one or more compounds of formula (V) and one or more compounds of formula (III), wherein the molar ratio of the compounds of formula (V) to the compounds of formula (III) is (0.05-1.1):1; or the phosphorus-containing mixture is a mixture comprising one or more compounds of formula (IV) and one or more compounds of formula (V), wherein the molar ratio of the compounds of formula (IV) to the compounds of formula (V) is (0.9-1.1):

1.

15. 15. The method of claim 14, wherein the phosphorus-containing mixture is a mixture of one or more compounds of formula (IV) and one or more compounds of formula (III), wherein the molar ratio of the compounds of formula (IV) to the compounds of formula (III) is (0.9-1.1):1; or the phosphorus-containing mixture is a mixture of one or more compounds of formula (V) and one or more compounds of formula (III), wherein the molar ratio of the compounds of formula (V) to the compounds of formula (III) is (0.9-1.1):1; or the phosphorus-containing mixture is a mixture comprising one or more compounds of formula (IV) and one or more compounds of formula (V), wherein the molar ratio of the compounds of formula (IV) to the compounds of formula (V) is (0.9-1.1):

1.

16. The process according to any one of claims 1 to 4, characterized in that in step a) or a1), the reaction temperature is from 20 to 200°C.

17. The method according to claim 16, characterized in that in step a) or a1), the reaction temperature is 90 to 140° C.

18. The process according to any one of claims 1 to 4, characterized in that step a) or a1) is carried out in the presence of a base.

19. 19. The process according to claim 18, characterized in that the base in step a) or a1) is an organic base or ammonia.

20. 20. The process according to claim 19, characterized in that the organic base in step a) or a1) is an organic amine.

21. 20. The process according to claim 19, characterized in that in step a) or a1), the organic base is selected from the group consisting of pyridine derivatives having 1 to 3 substituents bonded to one or more carbon atoms in the pyridine or heterocycle, piperidine derivatives having 1 to 3 substituents bonded to one or more carbon atoms in the piperidine or heterocycle.

22. 20. The process according to claim 19, characterized in that the organic base is selected from the group consisting of triethylamine, piperidine or pyridine.

23. The method according to any one of claims 1 to 4, characterized in that in step a) or a1), the molar ratio of the base to the total amount of the compound of formula (III) and the compound of formula (V) is (1-10):

1.

24. The process according to any one of claims 1 to 4, characterized in that in step a) or a1), the reaction is carried out under solvent-free conditions or in an inert solvent.

25. 25. The method according to claim 24, wherein in step a) or a1), the inert solvent is selected from any one or more of amide solvents, hydrocarbon solvents, halogenated hydrocarbon solvents, sulfone or sulfoxide solvents, ether solvents or ester solvents.

26. 25. The method according to claim 24, wherein in step a) or a1), the inert solvent is selected from any one or more of a benzene-based solvent, an amide-based solvent, a halogenated hydrocarbon-based solvent, an ether-based solvent, or an ester-based solvent.

27. 27. The method according to claim 26, wherein in step a) or a1), the inert solvent is a benzene-based solvent.

28. The method according to claim 24, wherein in step a) or a1), the inert solvent is at least one selected from the group consisting of chlorobenzene, trimethylbenzene, 1,4-dioxane, 1,2-dichloroethane, dimethylsulfoxide, N-methylpyrrolidone, N,N-dimethylformamide, petroleum ether, n-heptane, tetrahydrofuran, methyltetrahydrofuran, benzene, toluene, ethyl acetate, and butyl acetate.

29. 5. The method according to claim 1, wherein in step a) or a1), the molar ratio of the phosphorus-containing compound or mixture to the compound of formula (II) is 1:(0.8-10); or the molar ratio of the compound of formula (II) to the phosphorus-containing compound or mixture is 1:(0.8-10).

30. 30. The method of claim 29, wherein in step a) or a1), the molar ratio of the phosphorus-containing compound or mixture to the compound of formula (II) is 1:(1-3); or the molar ratio of the compound of formula (II) to the phosphorus-containing compound or mixture is 1:(1-3).

31. 5. The process according to claim 1, characterized in that in step b) or b1), an inorganic or organic acid is added.

32. 32. The method according to claim 31, characterized in that the inorganic acid is hydrochloric acid or sulfuric acid.

33. 5. The process according to claim 1, wherein in step b) or b1), the base is an inorganic base or an organic base.

34. 34. The process according to claim 33, characterized in that the base is an alkali metal hydroxide, an alkaline earth metal hydroxide, an alkali metal carbonate, an alkaline earth metal carbonate, an alkali metal bicarbonate or an alkaline earth metal bicarbonate.

35. The base is NaOH, KOH or Ba(OH) ２ 34. The method of claim 33, wherein

36. 5. The process according to claim 1, characterized in that in step b) or b1), the reaction temperature is from 20 to 150° C.

37. 1. A method for preparing L-glufosinate or a salt thereof, comprising: Reacting a compound of formula (IIa) with a compound of formula (IIIa), 【Chemistry 7】 Then, an acid is added to obtain L-glufosinate.

38. 38. The method of claim 37, wherein the acid is hydrochloric acid.

39. Use of a compound of formula (III) in the preparation of glufosinate or a salt thereof, or L-glufosinate or a salt thereof. 【Chemistry 8】 (In the formula, Hal ２ and R ２ is as defined in any one of claims 1 to 13.

40. Use of a compound of formula (IIIa) in the preparation of glufosinate or a salt thereof, or L-glufosinate or a salt thereof. 【Chemistry 9】

41. A mixture comprising: A mixture comprising one or more compounds of formula (IV) and one or more compounds of formula (III); or a mixture comprising one or more compounds of formula (V) and one or more compounds of formula (III); or a mixture comprising one or more compounds of formula (III), one or more compounds of formula (IV) and one or more compounds of formula (V). 【Chemistry 10】 (In the formula, Hal ２ , R ２ , R ３ and R ４ is as defined in any one of claims 1 to 13, with the proviso that R ２ , R ３ and R ４ None of these are methyl.)

42. A mixture comprising: a mixture comprising one or more compounds of formula (IV) and one or more compounds of formula (III), wherein the molar ratio of the compounds of formula (IV) to the compounds of formula (III) is (0.05-1.1):1; or said mixture comprising one or more compounds of formula (V) and one or more compounds of formula (III), wherein the molar ratio of the compounds of formula (V) to the compounds of formula (III) is (0.05-1.1):

1. 【Chemistry 11】 (In the formula, Hal ２ , R ２ , R ３ and R ４ is as defined in any one of claims 1 to 13.

43. 43. The mixture according to claim 42, characterized in that the mixture comprises one or more compounds of formula (IV) and one or more compounds of formula (III), wherein the molar ratio of the compounds of formula (IV) to the compounds of formula (III) is (0.9-1.1):1; or the mixture comprises one or more compounds of formula (V) and one or more compounds of formula (III), wherein the molar ratio of the compounds of formula (V) to the compounds of formula (III) is (0.9-1.1):

1.

44. 44. The mixture according to any one of claims 41 to 43, characterized in that the compound of formula (IV) is diethylmethylphosphonite and the compound of formula (V) is dichloro(methyl)phosphane.

45. 45. Use of a mixture according to any one of claims 41 to 44 in the preparation of glufosinate or a salt thereof, or L-glufosinate or a salt thereof.

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