A kind of synthetic method of L-phosphinothricin ammonium intermediate

Abstract

The invention discloses a synthetic method of L-phosphinothricin ammonium intermediate, (S)-2-aminobutyrolactone hydrochloride is added to hydrochloric acid, hydrogen chloride is passed through under normal pressure for heat preservation reaction, or closed heating and heat preservation reaction is carried out, hydrogen chloride can be selectively passed through during the closed heating and heat preservation reaction, the reaction is completed, cooling and crystallization, solid-liquid separation or decompression to remove low-boiling substances to obtain compound (III) directly added to alcohol R1-OH, hydrogen chloride and / or other protonic acids are added as catalysts to catalyze esterification, wherein R1 is a straight or branched alkyl of C1 to C6; after post-treatment, a target compound is obtained. The present invention has the advantages of mild reaction conditions, high yield, and high enantiomeric excess.

Description

Technical Field

[0001] The invention relates to the field of agricultural herbicides, and in particular to a method for synthesizing an L-glufosinate-ammonium intermediate. Background Art

[0002] Glufosinate-ammonium was developed and produced by Germany's Hoechst (now Bayer). Its chemical name is 4-[hydroxy(methyl)phosphonyl]-DL-homoalanine ammonium salt. It is a glutamine synthesis inhibitor and a non-selective contact herbicide. Its mechanism of action is to inhibit the activity of glutamine synthetase in plants, leading to the obstruction of glutamine synthesis, nitrogen metabolism disorders, and ammonium ion accumulation, thereby interfering with plant metabolism and causing plant death.

[0003] Glufosinate has the characteristics of broad weed control spectrum, high activity, low toxicity, easy degradation in soil, safety to crops, small drift, good environmental compatibility and rapid weed control. It can prevent and quickly kill more than 100 annual and perennial broad-leaved weeds and grass weeds such as crabgrass and ryegrass.

[0004] Ordinary glufosinate is a mixture of two enantiomers, but only the L-isomer is active and easily decomposed in the soil, with low toxicity to humans and animals. The vast majority of glufosinate products currently sold on the market are racemic mixtures. L-glufosinate not only reduces the dosage by half, significantly reducing environmental pressure, but also has better control effects on active and resistant weeds than ordinary glufosinate.

[0005] In the chemical synthesis of L-phosphinothricin, there are many literature reports and patents disclosing the synthesis methods of its important intermediate (S)-4-halo-2-aminobutyric acid ester and its salts.

[0006] The patent specification with the announcement number CN109369432B discloses that under the catalysis of organic or inorganic sulfonic acid, (S)-2-aminobutyrolactone undergoes ring-opening alcoholysis to obtain the corresponding S-homoserine ester, which is then chlorinated to obtain the target product.

[0007]

[0008] The patent specification with the announcement number CN110845347B discloses that: in an alcohol system, 2-aminobutyrolactone hydrochloride and thionyl chloride undergo chlorination and esterification reaction to prepare 4-chloro-2-aminobutyrate hydrochloride. Although the raw materials of this method are easy to obtain, the solubility of 2-aminobutyrolactone hydrochloride in alcohol is very poor, and the reaction conversion takes a long time due to poor mass transfer. In addition, the reaction will produce chloroalkanes and an equivalent amount of sulfur dioxide, which is not economical and environmentally friendly.

[0009]

[0010] The patent specification with publication number CN114163471A discloses that: using halogenated hydrocarbon or aromatic hydrocarbon as solvent, homoserine reacts with halogenated reagents such as dihalogenated sulfoxide, trihalogenated phosphorus, trihalide phosphorus, pentahalide phosphorus, etc. to obtain halogenated homoserine hydrochloride. The substrate homoserine has very poor solubility in the above solvents. At the same time, from the analysis of the reaction mechanism, the carboxyl group is more easily halogenated to an acyl halide, and at this time, intramolecular ring closure is very likely to occur to obtain 2-aminobutyrolactone salt. Therefore, the practicality of this process route is not strong.

[0011]

[0012] The patent specification with publication number US5442088A discloses that 2-aminobutyrolactone with different amino groups is heated to a predetermined temperature in an alcohol solution, and then hydrogen chloride gas is continuously introduced for several hours to prepare amino-protected 4-chloro-2-aminobutyrate. Although this method can perform chlorination and esterification in one step, a large amount of hydrogen chloride needs to be introduced during the reaction, and a large amount of chlorinated hydrocarbons will inevitably be produced. These substances are not only Class 3 carcinogens, but also have serious damage to the atmospheric environment, especially the ozone layer.

[0013]

[0014] In addition, there are also a large number of literature reports: homoserine or 2-aminobutyrolactone salt is heated in a hydrobromic acid glacial acetic acid solution to obtain bromohomoserine hydrobromide, which is then esterified to obtain 4-bromo-2-aminobutyrate and its salt [Chemistry-A European Journal (2013), 19 (13), 4244-4248; J. Org. Chem. 2008, 73, 1, 168-176; Chemical Communications (2019), 55 (54), 7860-7863]. These methods require the use of glacial acetic acid with a large excess of hydrobromic acid as a solvent, which has a high raw material cost. In addition, the esterification reaction of bromohomoserine cannot be carried out directly in the glacial acetic acid system. Bromohomoserine must be separated and purified from the glacial acetic acid system. Because it is extremely water-soluble, it is difficult to separate from glacial acetic acid and the yield is low.

[0015]

[0016] In recent years, with the growing demand for glufosinate, the L-enantiomer can significantly reduce the impact on the environment because its dosage is halved and its biodegradation rate is fast. At the same time, its activity and control effect on resistant weeds are also better than DL-glufosinate.

[0017] Therefore, developing a method for synthesizing L-glufosinate and its intermediates with mild reaction conditions, higher yield, lower cost, and simple operation is of great significance for reducing the amount of herbicides used and increasing their efficiency. Summary of the invention

[0018] When 2-aminobutyrolactone salt is used as a raw material and the target compound is prepared by thionyl chloride and alcohol system, a certain amount of by-product chlorinated hydrocarbons and an equivalent amount of sulfur dioxide gas will inevitably be produced, and the amount of three wastes is large; when hydrogen chloride is introduced into the alcohol system for reaction, a certain amount of chlorinated hydrocarbon gas will also inevitably be produced, and the consumption of hydrogen chloride is large, and a large amount of by-product hydrochloric acid will be produced. In addition, the solubility of 2-aminobutyrolactone salt or homoserine in alcohol is very low, and the poor mass transfer also leads to a significant extension of the reaction time.

[0019] In view of the above technical problems and the shortcomings in the art, the present invention provides a method for synthesizing an L-phosphinothricin intermediate, specifically a method for synthesizing (S)-4-chloro-2-aminobutyric acid ester (I) and its salt, wherein (S)-2-aminobutyrolactone hydrochloride is used as a raw material, firstly chlorinated in an aqueous phase system, and then esterified in alcohol under the action of a catalytic amount of protonic acid. The method has the advantages of mild reaction conditions, high yield, high enantiomeric excess, etc., and can be used for the synthesis of L-phosphinothricin.

[0020]

[0021] The specific technical solutions are as follows:

[0022] A method for synthesizing an L-phosphinothricin ammonium intermediate, the reaction scheme is as follows:

[0023]

[0024]

[0025] The specific steps include:

[0026] (1) adding compound (II) ((S)-2-aminobutyrolactone hydrochloride) to hydrochloric acid, and introducing hydrogen chloride to react under normal pressure, or heating in a sealed environment to react; hydrogen chloride may be introduced selectively during the sealed environment to react;

[0027] (2) After the reaction of step (1) is completed, the reaction is cooled and crystallized, and the compound (III) is obtained by solid-liquid separation or decompression to remove low-boiling substances, and the compound (III) is directly used in step (3); preferably, the compound (III) is obtained by solid-liquid separation and directly used in step (3);

[0028] (3) adding the compound (III) obtained in step (2) to the alcohol R1-OH, and adding a catalytic amount of hydrogen chloride and / or other protonic acid as a catalyst to catalyze the esterification reaction; the amount of the catalyst added is 1% to 40% of the molar amount of the compound (III);

[0029] R1 is a C1-C6 straight chain or branched chain alkyl;

[0030] (4) After post-treatment, the target compound (I) is obtained.

[0031] In a preferred embodiment, in the method for synthesizing the L-phosphinothionyl intermediate, in step (4), the post-treatment comprises the following steps:

[0032] (i) Post-esterification treatment:

[0033] a. removing the low boiling point substances under reduced pressure, adding an organic solvent to obtain a mixture; or,

[0034] b. Cooling and solid-liquid separation, the obtained solid is added to a mixture of water and an organic solvent to obtain a mixture;

[0035] (ii) adjusting the pH of the mixture obtained in step (i) to 6-9 (preferably 7-8), allowing it to stand for stratification, and distilling the organic phase under reduced pressure to obtain the target compound (I).

[0036] Furthermore, in step (i), the organic solvent is preferably at least one of toluene, (o-, m-, p-)xylene, (me-, iso-)trimethylbenzene, ethylbenzene, (o-, m-, p-)diethylbenzene, isopropylbenzene, (o-, m-, p-)diisopropylbenzene, monohalobenzene, dihalobenzene, dichloromethane, chloroform, carbon tetrachloride, ethylene dichloride, ethyl acetate, isopropyl acetate, and butyl acetate.

[0037] In the method for synthesizing the L-glufosinate intermediate, in step (1), during the closed heating and heat preservation reaction, the pressure of the reaction system is preferably 0.1 to 10.0 atm, and more preferably 0.5 to 5.0 atm.

[0038] In the method for synthesizing the L-phosphinothricin intermediate, in step (1), the temperature of the insulation reaction is preferably 50 to 130° C., and more preferably 90 to 110° C.

[0039] In the method for synthesizing the L-phosphinothricin intermediate, in step (1), the molar ratio of hydrochloric acid to compound (II) is preferably 1 to 15:1, and more preferably 1.5 to 4.5:1, calculated as HCl.

[0040] In the method for synthesizing the L-phosphinothricin intermediate, in step (1), the mass concentration of the hydrochloric acid is preferably 20% to 40%, and more preferably 30% to 36%.

[0041] In the method for synthesizing the L-phosphinothricin intermediate, in step (1), the molar ratio of the amount of hydrogen chloride introduced to compound (II) is preferably 1 to 5:1, and more preferably 1.5 to 3:1.

[0042] In the synthesis method of the L-glufosinate intermediate, in step (3), alcohol R1-OH is used as a solvent and a reactant.

[0043] In the method for synthesizing the L-phosphinothricin intermediate, in step (3), R1 is preferably methyl, ethyl or isopropyl.

[0044] In the method for synthesizing the L-glufosinate intermediate, in step (3), the weight ratio of alcohol R1-OH to compound (III) is preferably 0.8 to 10:1, and more preferably 1 to 5:1.

[0045] In the method for synthesizing the L-phosphinothricin intermediate, in step (3), the hydrogen chloride can be added in the form of gas or solution.

[0046] In the method for synthesizing the L-glufosinate intermediate, in step (3), the other protonic acid is preferably at least one of sulfuric acid, phosphoric acid, polyphosphoric acid, and boric acid.

[0047] Furthermore, in the method for synthesizing the L-phosphinothricin intermediate, in step (3), the catalyst is preferably at least one of hydrogen chloride gas, sulfuric acid, and phosphoric acid.

[0048] In the method for synthesizing the L-phosphinothricin intermediate, in step (3), the amount of the catalyst added is preferably 1% to 15% of the molar amount of compound (III).

[0049] In the method for synthesizing the L-phosphinothricin intermediate, in step (3), the temperature of the esterification reaction is preferably 10 to 150° C., and more preferably 15 to 80° C.

[0050] The technical solution disclosed in the patent specification with publication number US5442088A requires the amino group of 2-aminobutyrolactone to be protected because hydrogen chloride is continuously introduced into alcohol for a one-step chlorination and esterification reaction. Otherwise, the solubility of the hydrochloride of 2-aminobutyrolactone in alcohol is extremely poor, resulting in a slow reaction conversion. At the same time, amino group protection means a waste of raw materials related to the protecting group and an increase in production costs. Accordingly, the patented technology requires the continuous introduction of a large amount of hydrogen chloride, which increases the cost of raw materials and inevitably increases the pressure on the treatment and disposal of waste ethyl chloride and excess hydrogen chloride gas.

[0051] Compared with the prior art, the present invention has the following beneficial effects:

[0052] 1. The synthesis method of the present invention can avoid the use of hydrogen bromide glacial acetic acid solution, and also avoid the generation of mixed salts (hydrobromide and hydrochloride) during bromination, thereby reducing the cost of raw materials and the cost of treating by-product salts. It can also avoid the generation of by-product chlorinated hydrocarbons and equivalent sulfur dioxide gas when using thionyl chloride and alcohol systems, thereby reducing the amount of three wastes;

[0053] 2. First, the chlorination reaction is carried out in an aqueous phase system. Compound (II) does not need to be protected by the amino group and is directly added in the form of hydrochloride. Then, an esterification reaction is carried out by a catalytic amount of acid. At the same time, the problem of continuously introducing hydrogen chloride into the alcohol system to react and produce a large amount of chlorohydrocarbons can be avoided, thereby improving the yield and purity of the target product.

[0054] 3. The single batch yield of the target compound (I) can reach about 85% by using the synthesis method of the present invention. On this basis, after the mother liquor of the first step is recycled, the comprehensive yield is 90-95%. At the same time, under this condition, the raw material and the product are not easy to racemize, and the ee value can be stabilized at more than 98.5%;

[0055] 4. After solid-liquid separation, compound (III) can be directly used in the next reaction without purification, which reduces the number of steps and the production cost.

[0056] In summary, the reaction raw materials of the present invention are easily available, the process is simple unit operation, the reaction equipment requirements are low, the reaction conditions are mild, the yield and content are high, and it is suitable for industrial production. DETAILED DESCRIPTION

[0057] The present invention will be further described below in conjunction with specific examples. It should be understood that these examples are only intended to illustrate the present invention and are not intended to limit the scope of the present invention. The operating methods in the following examples where no specific conditions are indicated are usually carried out under conventional conditions or under conditions recommended by the manufacturer.

[0058] Example 1

[0059] Preparation method of (S)-4-chloro-2-aminobutyric acid ethyl ester (Ia):

[0060]

[0061] (S)-2-Aminobutyrolactone hydrochloride (120.0 g, 0.872 mol, 1.0 eq.) and 30% hydrochloric acid (233.2 g, 1.919 mol, 2.2 eq.) were placed in an autoclave, heated and kept warm at 95-100 degrees, and reacted for 5 hours. During this process, the maximum pressure in the autoclave was 1.6 atm. The temperature was lowered and filtered to obtain 134.14 g of a crude product of compound (III) with a content of 97.1% and a yield of 85.8%.

[0062] The crude product of the above compound (III) was put into ethanol (260g, 2w / w), and hydrogen chloride (1.36g, 0.037mol, 0.05eq.) was slowly introduced at 25-30 degrees. After ventilation, the temperature was slowly raised to 50-55 degrees, and the reaction was kept warm for 3 hours. After the reaction was completed, the low-boiling substances were removed under reduced pressure, 150g of deionized water and 150g of dichloromethane were added, and after stirring evenly, the pH was adjusted to 7-8 with ammonia water, and the mixture was allowed to stand for stratification. The aqueous phase was extracted once with dichloromethane, and the organic phases were combined. The obtained organic phase was first desolventized to recover the solvent, and then distilled under reduced pressure. The intermediate fraction, i.e., the target compound Ⅰa, was collected, which was 116.29g, with a content of 98.5%, a yield of 92.4%, and an ee value of 99.2%.

[0063] Example 2

[0064] Preparation method of (S)-4-chloro-2-aminobutyric acid methyl ester (Ib):

[0065]

[0066] (S)-2-Aminobutyrolactone hydrochloride (120.0 g, 0.872 mol, 1.0 eq.) and 30% hydrochloric acid (222.6 g, 1.832 mol, 2.1 eq.) were placed in an autoclave, heated and kept warm at 95-100 degrees, and reacted for 5 hours. During this process, the maximum pressure in the autoclave was 1.4 atm. The temperature was lowered and filtered to obtain 133.32 g of a crude product of compound (III) with a content of 96.1% and a yield of 84.4%.

[0067] The crude product of the above compound (III) was put into methanol (260g, 2w / w), and hydrogen chloride (2.7g, 0.074mol, 0.1eq.) was slowly introduced at 25-30 degrees. After ventilation, the temperature was slowly raised to 50-55 degrees, and the reaction was kept warm for 3 hours. After the reaction was completed, the low-boiling substances were removed under reduced pressure, 120g of deionized water and 120g of dichloromethane were added, and after stirring evenly, the pH was adjusted to 7-8 with ammonia water, and the mixture was allowed to stand for stratification. The aqueous phase was extracted once with dichloromethane, and the organic phases were combined. The obtained organic phase was first desolventized to recover the solvent, and then distilled under reduced pressure. The intermediate fraction, i.e., the target compound Ⅰb, was collected, which was 107.4g, with a content of 98.1%, a yield of 94.4%, and an ee value of 98.5%.

[0068] Example 3

[0069] Preparation method of (S)-4-chloro-2-aminobutyric acid ethyl ester (Ia):

[0070]

[0071] (S)-2-Aminobutyrolactone hydrochloride (120.0 g, 0.872 mol, 1.0 eq.) and 30% hydrochloric acid (212.04 g, 1.745 mol, 2.0 eq.) were put into a reaction flask, heated and kept warm at 85-90 degrees, and hydrogen chloride gas (about 63 g) was slowly introduced. After reacting for 2 hours, the temperature was cooled and filtered to obtain 113.98 g of crude compound (III) with a content of 93.5% and a yield of 70.2%.

[0072] The crude product of the above compound (III) was put into ethanol (220g, 2w / w), and hydrogen chloride (1.12g, 0.031mol, 0.05eq.) was slowly introduced at 25-30 degrees. After ventilation, the temperature was slowly raised to 50-55 degrees, and the reaction was kept warm for 3 hours. After the reaction was completed, the low-boiling substances were removed under reduced pressure, 150g of deionized water and 150g of dichloromethane were added, and after stirring evenly, the pH was adjusted to 7-8 with ammonia water, and the layers were allowed to stand for stratification. The aqueous phase was extracted once with dichloromethane, and the organic phases were combined. The obtained organic phase was first desolventized to recover the solvent, and then distilled under reduced pressure. The intermediate fraction, i.e., the target compound Ⅰa, was collected, which was 97.26g, with a content of 97.4%, a yield of 93.4%, and an ee value of 99.3%.

[0073] Example 4

[0074] Preparation method of (S)-4-chloro-2-aminobutyric acid methyl ester (Ib):

[0075]

[0076] (S)-2-Aminobutyrolactone hydrochloride (120.0 g, 0.872 mol, 1.0 eq.) and 30% hydrochloric acid (212.04 g, 1.745 mol, 2.0 eq.) were put into a reaction flask, heated and kept warm at 85-90 degrees, and hydrogen chloride gas (about 80 g) was slowly introduced. After reacting for 2 hours, the temperature was cooled and filtered to obtain 117.44 g of a crude product of compound (III) with a content of 94.1% and a yield of 72.8%.

[0077] The crude product of the above compound (III) was put into methanol (240g, 2w / w), and hydrogen chloride (1.16g, 0.032mol, 0.05eq.) was slowly introduced at 25-30 degrees. After ventilation, the temperature was slowly raised to 50-55 degrees, and the reaction was kept warm for 3 hours. After the reaction was completed, the low-boiling substances were removed under reduced pressure, 120g of deionized water and 120g of dichloromethane were added, and after stirring evenly, the pH was adjusted to 7-8 with ammonia water, and the mixture was allowed to stand for stratification. The aqueous phase was extracted once with dichloromethane, and the organic phases were combined. The obtained organic phase was first desolventized to recover the solvent, and then distilled under reduced pressure. The intermediate fraction, i.e., the target compound Ib, was collected, which was 101.13g, with a content of 96.1%, a yield of 92.4%, and an ee value of 99.5%.

[0078] Example 5

[0079] Preparation method of (S)-4-chloro-2-aminobutyric acid ethyl ester (Ia):

[0080]

[0081] (S)-2-Aminobutyrolactone hydrochloride (120.0 g, 0.872 mol, 1.0 eq.) and 30% hydrochloric acid (265.05 g, 2.181 mol, 2.5 eq.) were placed in an autoclave, heated and kept warm at 95-100 degrees, and reacted for 5 hours. During this process, the maximum pressure in the autoclave was 2.0 atm. The temperature was lowered and filtered to obtain 137.02 g of a crude compound (III) with a content of 96.5% and a yield of 87.1%.

[0082] The crude product of the above compound (III) was put into ethanol (260g, 2w / w), and sulfuric acid (14.89g, 0.152mol, 0.2eq.) was slowly added dropwise at 25-30 degrees. After the addition was completed, the temperature was raised to 50-55 degrees, and the reaction was kept warm for 5 hours. After the reaction was completed, the low-boiling substances were removed under reduced pressure, and 150g of deionized water and 150g of dichloromethane were added. After stirring evenly, the pH was adjusted to 7-8 with sodium carbonate solution, and the mixture was allowed to stand for stratification. The aqueous phase was extracted once with dichloromethane, and the organic phases were combined. The obtained organic phase was first desolventized to recover the solvent, and then distilled under reduced pressure. The intermediate fraction, i.e., the target compound Ⅰa, was collected, which was 109.89g, with a content of 97.8%, a yield of 85.4%, and an ee value of 99.1%.

[0083] Example 6

[0084] Preparation method of (S)-4-chloro-2-aminobutyric acid methyl ester (Ib):

[0085]

[0086] (S)-2-Aminobutyrolactone hydrochloride (120.0 g, 0.872 mol, 1.0 eq.) and 30% hydrochloric acid (264.0 g, 2.172 mol, 2.5 eq.) were placed in an autoclave, heated and kept warm at 95-100 degrees, and reacted for 5 hours. During this process, the maximum pressure in the autoclave was 2.0 atm. The temperature was lowered and filtered to obtain 138.59 g of a crude product of compound (III) with a content of 96.5% and a yield of 88.1%.

[0087] The crude product of the above compound (III) was put into methanol (270g, 2w / w), and sulfuric acid (7.53g, 0.077mol, 0.1eq.) was slowly added dropwise at 25-30 degrees. After the addition was completed, the temperature was raised to 50-55 degrees, and the reaction was kept warm for 5 hours. After the reaction was completed, the low-boiling substances were removed under reduced pressure, 160g of deionized water and 160g of dichloromethane were added, and after stirring evenly, the pH was adjusted to 7-8 with sodium carbonate solution, and the mixture was allowed to stand for stratification. The aqueous phase was extracted once with 120g of dichloromethane, and the organic phases were combined. The obtained organic phase was first desolventized to recover the solvent, and then distilled under reduced pressure. The intermediate fraction, i.e., the target compound Ib, was collected, which was 115.76g, with a content of 96.1%, a yield of 87.4%, and an ee value of 99.0%.

[0088] Example 7

[0089] Preparation method of (S)-4-chloro-2-aminobutyric acid ethyl ester (Ia):

[0090]

[0091] (S)-2-Aminobutyrolactone hydrochloride (120.0 g, 0.872 mol, 1.0 eq.) and 30% hydrochloric acid (243.84 g, 2.006 mol, 2.3 eq.) were placed in an autoclave, heated and kept warm at 95-100 degrees for 5 hours. During this process, the maximum pressure in the autoclave was 1.7 atm. The temperature was lowered and filtered to obtain 131.48 g of a crude compound (III) with a content of 97.1% and a yield of 84.1%.

[0092] The crude product of the above compound (III) was put into ethanol (260g, 2w / w), and hydrogen chloride (1.34g, 0.039mol, 0.05eq.) was slowly introduced at 25-30 degrees. After ventilation, the temperature was slowly raised to 50-55 degrees, and the reaction was kept warm for 3 hours. After the reaction was completed, the temperature was cooled and filtered, and the filter cake was added to a mixture of 150g deionized water and 150g dichloromethane. After stirring evenly, the pH was adjusted to 7-8 with sodium carbonate solution, and the layers were allowed to stand for stratification. The aqueous phase was extracted once with dichloromethane, and the organic phases were combined. The obtained organic phase was first desolventized to recover the solvent, and then decompressed and distilled. The intermediate fraction, i.e., the target compound Ia, was collected, which was 112.33g, with a content of 96.9%, a yield of 89.4%, and an ee value of 98.9%.

[0093] In addition, it should be understood that after reading the above description of the present invention, those skilled in the art may make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the claims attached to this application.

Claims

1. A method for synthesizing an L-phosphinothricin intermediate, characterized in that: The reaction route is as follows: The specific steps include: (1) adding compound (II) to hydrochloric acid and performing a closed heating and heat preservation reaction; hydrogen chloride can be selectively introduced during the closed heating and heat preservation reaction; the temperature of the heat preservation reaction is 90 to 110° C.; during the closed heating and heat preservation reaction, the pressure of the reaction system is 0.5 to 5.0 atm; The molar ratio of hydrochloric acid to compound (II) is 2.1 to 2.5:1, calculated as HCl; The mass concentration of the hydrochloric acid is 30% to 36%; The molar ratio of the amount of hydrogen chloride introduced to the compound (II) is 1.5 to 3:1; (2) After the reaction of step (1) is completed, the mixture is cooled and crystallized, and the solid-liquid separation is performed to obtain compound (III), which is directly used in step (3). Optionally, the mother liquor is recycled; (3) adding the compound (III) obtained in step (2) to the alcohol R1-OH, and adding a catalytic amount of hydrogen chloride and / or other protonic acid as a catalyst to catalyze the esterification reaction; the amount of the catalyst added is 1% to 40% of the molar amount of the compound (III); R1 is a C1-C6 straight chain or branched chain alkyl; (4) After post-treatment, the target compound (I) is obtained.

2. The method for synthesizing the L-phosphinothricin-ammonium intermediate according to claim 1, characterized in that: In step (4), the post-processing comprises the following steps: (i) Post-esterification treatment: a. removing the low boiling point substances under reduced pressure, adding an organic solvent to obtain a mixture; or, b. Cooling and solid-liquid separation, the obtained solid is added to a mixture of water and an organic solvent to obtain a mixture; (ii) The mixture obtained in step (i) is adjusted to a pH of 6 to 9, and then allowed to stand to separate the layers. The organic phase is distilled under reduced pressure to obtain the target compound (I).

3. The method for synthesizing the L-phosphinothricin-ammonium intermediate according to claim 1, characterized in that: In step (3), R1 is methyl, ethyl or isopropyl.

4. The method for synthesizing the L-phosphinothricin-ammonium intermediate according to claim 1, characterized in that: In step (3), the weight ratio of alcohol R1-OH to compound (III) is 0.8 to 10:

1.

5. The method for synthesizing the L-phosphinothricin-ammonium intermediate according to claim 4, characterized in that: In step (3), the weight ratio of alcohol R1-OH to compound (III) is 1 to 5:

1.

6. The method for synthesizing the L-phosphinothricin intermediate according to claim 1, characterized in that: In step (3): The hydrogen chloride is added in the form of gas or solution; The other protonic acid is at least one of sulfuric acid, phosphoric acid, polyphosphoric acid and boric acid.

7. The method for synthesizing the L-phosphinothricin-ammonium intermediate according to claim 1, characterized in that: In step (3), the amount of the catalyst added is 1% to 15% of the molar amount of compound (III).

8. The method for synthesizing the L-phosphinothricin-ammonium intermediate according to claim 1, characterized in that: In step (3), the temperature of the esterification reaction is 10 to 150°C.

9. The method for synthesizing the L-phosphinothricin-ammonium intermediate according to claim 8, characterized in that: In step (3), the temperature of the esterification reaction is 15 to 80°C.

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