Synthesis method of cefpodoxime axetil intermediate 7-AMCA

Abstract

The invention discloses a method for synthesizing a cefpodoxime proxetil intermediate 7-AMCA, and belongs to the technical field of cefpodoxime proxetil intermediate synthesis. The method is characterized in that a starting material D-7ACA is dissolved in a polar solvent liquid, and under the catalysis of an alkaline catalyst, elemental iodine is added to complete an iodination reaction, and then methanol is added to complete a methylation reaction to obtain a polar solvent liquid containing 7-AMCA. The method has the beneficial effects of using cesium acetate or cesium formate as an alkaline catalyst to carry out the methylation reaction, avoiding the use of reagents such as boron trifluoride and methanesulfonic acid, effectively reducing the risk factor, and the reaction reagents and solvents are non-highly toxic, and the harm to the environment and the human body can be almost ignored. The molar yield of the process can reach 85% or more, the product purity is 97.5% or more, and the by-product lactone is controlled to be below 0.3%.

Description

Technical field:

[0001] The invention belongs to the technical field of synthesis of cefpodoxime proxetil intermediates, and more particularly relates to a method for synthesizing the cefpodoxime proxetil intermediate 7-AMCA. Background technology:

[0002] 7-Amino-3-methoxymethyl-3-cephem-4-carboxylic acid (7-AMCA for short) is a key intermediate in the synthesis of the third-generation antibacterial drug cefpodoxime proxetil. Its structural formula is as follows:

[0003]

[0004] At present, there are many reports, most of which are converted from 7-aminocephalosporanic acid (7-ACA), and a few use D-7ACA as the starting material. For example:

[0005] EP204,657: 7-ACA is reacted with boron trifluoride-methanol in sulfolane to produce 7-AMCA, but this method requires the use of dangerous gaseous boron trifluoride.

[0006] EP262,744: 7-ACA and methanol are reacted in the presence of antimony chloride or zinc chloride to prepare 7-AMCA. However, this method easily forms a colloidal compound that is very difficult to filter, and the product yield obtained by this method is also relatively low (about 40%).

[0007] JP82,192,392 and US4,482,710: This patent first adds a phenylacetyl protecting group to the amino group at position 7 of 7-ACA. The acetoxy group on 7-ACA is then converted to a methoxy group using methanol-calcium chloride, and the protecting group is removed. This method is cumbersome and requires multiple steps, resulting in a low product yield (only 20%).

[0008] EP0,485,204: 7-ACA is directly methylated to obtain 7-AMCA using 7-ACA as raw material, sulfolane as solvent, and trimethyl borate as catalyst. This method requires the use of expensive trimethyl borate, is not economically feasible, and is highly polluting to the environment.

[0009] JP84,163,387: 7-ACA is treated with methanesulfonic acid-methanol to prepare 7-AMCA. This method also has the problem of low yield (30%) and low product purity due to the formation of by-product lactone.

[0010] CN102746322A: Using 7-ACA as a substrate, boron trifluoride-methanol as a catalyst, and sodium methoxide as a methylating agent, the strong base effect of sodium methoxide can easily cause local over-alkalinity, thereby forming a large amount of lactone and causing β-lactam ring opening, resulting in low product purity and uncontrollable industrial large-scale production.

[0011] CN109956958B: Using D-7ACA as a substrate, an alkylating agent is added to react under the catalysis of a strong acid such as methanesulfonic acid. This method uses the highly acidic methanesulfonic acid in the reaction, which not only increases the content of the byproduct lactone but also easily corrodes the plant equipment, making it difficult to scale up.

[0012] The by-product lactones produced in the above-mentioned references have various forms, and the more common chemical formula of the by-product lactone is:

[0013]

[0014] Since it is difficult to remove this impurity, the product quality and yield are reduced.

[0015] In summary, all of the above methods have various challenges: some require multiple steps and result in low product yields; some use expensive catalysts, making them economically unfeasible; some produce high levels of lactone byproducts, resulting in low product purity; and some are difficult to filter on a large scale, making industrial production time-consuming and inefficient. Therefore, developing an environmentally friendly, economically viable, and high-purity 7-AMCA synthesis method is a current research hotspot. Summary of the invention:

[0016] To solve the above problems and overcome the shortcomings of the existing technology, the present invention provides a method for synthesizing 7-AMCA, an intermediate of cefpodoxime axetil, which can effectively solve the problems of multiple synthesis steps, low product yield, relatively expensive catalysts, and high content of lactone by-products in the existing synthesis process.

[0017] The specific technical solution of the present invention to solve the above technical problems is: a method for synthesizing the cefpodoxime axetil intermediate 7-AMCA, characterized in that: the starting material D-7ACA is dissolved in a polar solvent liquid, and under the catalysis of an alkaline catalyst, elemental iodine is added to complete the iodination reaction, and then methanol is added and a methylation reaction is completed to obtain a polar solvent liquid containing 7-AMCA.

[0018] Furthermore, the synthesis method of the cefpodoxime proxetil intermediate 7-AMCA comprises:

[0019] (1) Dissolving the starting material D-7ACA in a polar solvent to obtain a D-7ACA polar solvent solution;

[0020] (2) adding an alkaline catalyst to the obtained D-7ACA polar solvent solution;

[0021] (3) Controlling the reaction temperature at -30 to 50°C, adding elemental iodine to the above reaction solution, and reacting for 30 to 60 minutes;

[0022] (4) The reaction temperature is controlled at -30 to 50°C, methanol is added to the above reaction solution, and the reaction time is 30 to 120 minutes to obtain a polar solvent solution containing 7-AMCA.

[0023] Furthermore, the base catalyst is cesium acetate or cesium formate or a mixture of the two.

[0024] Furthermore, the molar ratio of the D-7ACA to the base catalyst is 1:1.3-4.0.

[0025] Furthermore, the polar solvent liquid is sulfone, ether or ester or a mixture thereof.

[0026] Furthermore, the mass volume ratio of the D-7ACA to the solvent is 1:5-40.

[0027] Furthermore, the molar ratio of the D-7ACA to elemental iodine is 1:1.2 to 3.0.

[0028] Furthermore, the molar ratio of the D-7ACA to methanol is 1:2.5-4.5.

[0029] Furthermore, the polar solvent solution of 7-AMCA is added to a mixture of water and an organic solvent at 0-5° C., and the mixture is extracted by stratification. The aqueous phase is taken, and the pH is adjusted to 2.0-3.0 with acid solution. The mixture is filtered and dried to obtain 7-AMCA.

[0030] Furthermore, the organic solvent is dichloromethane or ethyl acetate or toluene

[0031] The beneficial effects of the present invention are:

[0032] Beneficial effects of the present invention:

[0033] The invention uses cesium acetate or cesium formate as a base catalyst to carry out the methylation reaction, avoiding the use of reagents such as boron trifluoride and methanesulfonic acid, which can effectively reduce the risk factor and facilitate operation. The reaction reagents and solvents used in the present invention are non-highly toxic and the harm to the environment and human body is almost negligible. The molar yield of this process can reach 85% or more, the product purity is 97.5% or more, and the by-product lactone is controlled below 0.3%.

[0034] This invention uses cesium acetate or cesium formate as a base catalyst, creatively playing the role of a dual catalyst in the iodination and methylation reactions, greatly promoting the reaction of 7-AMCA and avoiding the occurrence of side reactions. Description of the drawings:

[0035] Attachment Figure 1 This is a liquid phase detection chromatogram of Example 1 of the present invention;

[0036] Attachment Figure 2 This is a liquid phase detection chromatogram of Example 2 of the present invention;

[0037] Attachment Figure 3 This is a liquid phase detection chromatogram of Example 3 of the present invention;

[0038] Attachment Figure 4 This is a liquid phase detection chromatogram of Example 4 of the present invention;

[0039] Attachment Figure 5 This is a liquid phase detection chromatogram of Comparative Example 1 of the present invention;

[0040] Attachment Figure 6 This is the liquid phase detection chromatogram of Comparative Example 2 of the present invention;

[0041] Attachment Figure 7 This is a liquid phase detection chromatogram of Comparative Example 3 of the present invention;

[0042] Attachment Figure 8 This is a liquid phase detection chromatogram of Comparative Example 4 of the present invention;

[0043] Attachment Figure 9 This is a liquid phase detection chromatogram of Comparative Example 5 of the present invention;

[0044] Attachment Figure 10 This is a liquid phase detection chromatogram of Comparative Example 6 of the present invention;

[0045] Attachment Figure 11 This is a liquid phase detection chromatogram of Comparative Example 7 of the present invention;

[0046] Attachment Figure 12 This is a liquid phase detection chromatogram of Comparative Example 8 of the present invention;

[0047] Attachment Figure 13 The liquid phase detection conditions and the test sample detection chromatogram of the present invention; Specific implementation method:

[0048] In the description of the present invention, specific details are provided solely to facilitate a thorough understanding of the embodiments of the present invention. However, those skilled in the art will appreciate that the present invention is not limited to these details. Furthermore, well-known structures and functions have not been described or illustrated in detail to avoid obscuring the key points of the embodiments of the present invention. Those skilled in the art will appreciate the specific meanings of the above terms as used in the present invention.

[0049] Specific implementation of the present invention:

[0050] In order to better understand the present invention, a specific embodiment is used for illustration. It is worth emphasizing that the effects of this embodiment are not substantially different from those of various embodiments within the scope of protection of the present invention, including the respective reagents and the content ratios of the reagents. All of them can achieve the effects described in the present invention and solve the above-mentioned problems. Other combinations are not described here.

[0051] Example 1:

[0052] Place 11.5 g (0.05 mol) of D-7ACA in a three-necked flask, add 136 ml of sulfolane as the reaction solvent, stir evenly, cool to -20 to -10°C, add 19.19 g (0.10 mol) of cesium acetate with stirring, control the temperature at -20 to -10°C, slowly add 19.05 g (0.075 mol) of elemental iodine, control the temperature at -5 to 5°C, and react for 45 minutes. Then, add 4.80 g (0.15 mol) of methanol, raise the temperature to 10-20°C, and time the reaction for 1 hour.

[0053] After the reaction, 250 ml of cold water at 3-7° C. was added to the reaction solution to quench the reaction, then the temperature was raised to 20-25° C., 350 ml of ethyl acetate was added, and extraction was carried out for 15 minutes. The phases were allowed to stand and separated, and the organic phase was discarded. The aqueous phase was extracted with 50 ml of ethyl acetate for 15 minutes, and the phases were allowed to stand and separated. The organic phase was discarded. The pH of the aqueous phase was adjusted to 2.5 with 1% dilute hydrochloric acid solution, and then the reaction mixture was crystallized at 20-25° C. for 0.5 hours, then cooled to 0-5° C. for crystallization for 2 hours, and filtered to obtain 10.37 g of the target product 7-AMCA; wherein the product molar yield was 85.1% and the purity was 97.9%.

[0054] 1HNMR(CF3COOD): 3.47(s,3H,O-CH3); 3.85(s,2H,-CH2-S); 4.53(s,2H,-CH2-O-CH3); 5.51(d,2H,-CH-CH-S);

[0055] Example 2:

[0056] Place 11.5 g (0.05 mol) of D-7ACA in a three-necked flask with 136 ml of sulfolane as the reaction solvent. Stir thoroughly, cool to -20-10°C, add 17.79 g (0.10 mol) of cesium formate with stirring, maintain the temperature at -5-5°C, then slowly add 25.40 g (0.10 mol) of elemental iodine. Allow to react at 10-20°C for 55 minutes. Then add 4.80 g (0.15 mol) of methanol, raise the temperature to 0-10°C, and time the reaction for 1 hour.

[0057] After the reaction, 250 ml of cold water at 3-7 ° C was added to the reaction solution to quench the reaction, then the temperature was raised to 20-25 ° C, 350 ml of ethyl acetate was added, and extraction was carried out for 15 min. The phases were allowed to stand and separated, and the organic phase was discarded. The aqueous phase was extracted with 50 ml of ethyl acetate for 15 min, and the phases were allowed to stand and separated. The organic phase was discarded. The pH of the aqueous phase was adjusted to 2.6 with 1% dilute sulfuric acid solution, and then crystallized at 20-25 ° C for 0.5 h, then cooled to 0-5 ° C for crystallization for 2 h, and filtered to obtain 10.50 g of the target product 7-AMCA, wherein the molar yield of the product was 86.1% and the purity was 98.0%;

[0058] 1HNMR(CF3COOD): 3.47(s,3H,O-CH3); 3.85(s,2H,-CH2-S); 4.53(s,2H,-CH2-O-CH3); 5.51(d,2H,-CH-CH-S);

[0059] Example 3

[0060] Place 6.90g (0.03mol) of D-7ACA in a three-necked flask with 108ml of dimethyl carbonate as the reaction solvent. Stir thoroughly, then cool to -20-10°C. Add 11.51g (0.06mol) of cesium acetate with stirring, maintaining the temperature at -5-5°C. Slowly add 17.78g (0.07mol) of elemental iodine, maintaining the temperature at 10-20°C and allowing the reaction to proceed for 40 minutes. Then, add 3.84g (0.12mol) of methanol, raise the temperature to 0-10°C, and time the reaction for 1 hour.

[0061] After the reaction, 150 ml of cold water at 3-7° C. was added to the reaction solution to quench the reaction, then the temperature was raised to 20-25° C., 200 ml of dichloromethane was added, and the mixture was extracted for 15 min. The mixture was allowed to stand for phase separation, and the organic phase was discarded. The aqueous phase was extracted with 40 ml of dichloromethane for 15 min, allowed to stand for phase separation, and the organic phase was discarded. The pH of the aqueous phase was adjusted to 2.3 with 2% phosphoric acid solution, and then the mixture was crystallized at 20-25° C. for 0.5 h, then cooled to 0-5° C. for crystallization for 2 h, and filtered to obtain 6.13 g of the target product 7-AMCA. The product had a molar yield of 83.8% and a purity of 98.2%.

[0062] 1HNMR(CF3COOD): 3.47(s,3H,O-CH3); 3.85(s,2H,-CH2-S); 4.53(s,2H,-CH2-O-CH3); 5.51(d,2H,-CH-CH-S);

[0063] Example 4

[0064] Place 23.0 g (0.10 mol) of D-7ACA in a three-necked flask with 450 ml of tetrahydrofuran as the reaction solvent. Stir thoroughly, cool to -20-10°C, add 39.14 g (0.22 mol) of cesium formate with stirring, maintain the temperature at -5-5°C, then slowly add 50.80 g (0.20 mol) of elemental iodine. Allow to react for 55 minutes at 10-20°C, then add 4.80 g (0.15 mol) of methanol. Raise the temperature to 0-10°C and time the reaction for 1 hour.

[0065] After the reaction, 700 ml of cold water at 3-7° C. was added to the reaction solution to quench the reaction, then the temperature was raised to 20-25° C., 1000 ml of toluene was added, and extraction was carried out for 15 min. The phases were allowed to stand and the organic phase was discarded. The aqueous phase was extracted with 150 ml of toluene for 15 min, the phases were allowed to stand and the organic phase was discarded. The pH was adjusted to 2.8 with 1% dilute sulfuric acid, and then the solution was grown at 20-25° C. for 0.5 h, then cooled to 0-5° C. for 2 h, and filtered to obtain 20.80 g of the target product 7-AMCA. The product had a molar yield of 85.3% and a purity of 98.3%.

[0066] 1HNMR(CF3COOD): 3.47(s,3H,O-CH3); 3.85(s,2H,-CH2-S); 4.53(s,2H,-CH2-O-CH3); 5.51(d,2H,-CH-CH-S);

[0067] Table 1: Product quality test results of different examples

[0068]

[0069] From the data analysis in Table 1, we can see that:

[0070] The present invention uses cesium acetate or cesium formate as a base catalyst to carry out the methylation reaction, avoiding the use of reagents such as boron trifluoride and methanesulfonic acid, which can effectively reduce the risk factor and facilitate operation. The reaction reagents and solvents used in the present invention are non-toxic and their harm to the environment and human body is almost negligible. The molar yield of the process can reach 85% or more, the product purity is 97.5% or more, and the by-product lactone is controlled below 0.3%.

[0071] In order to more intuitively demonstrate the product advantages of the present invention, the present invention is a synthesis method of cefpodoxime axetil intermediate 7-AMCA and

[0072] Comparative Example 1: Prior Art I - (according to national invention patent CN102746322A: using 7-ACA as substrate, boron trifluoride-methanol as catalyst, sodium methoxide as methylation reagent to prepare 7-AMCA, introduced by reference),

[0073] Comparative Example 2: Existing Technology II - (according to national invention patents CN102746322A: CN109956958B: using D-7ACA as a substrate, adding an alkylating agent to react under the catalysis of a strong acid such as methanesulfonic acid to prepare 7-AMCA, introduced by reference),

[0074] Table 2: Comparative data of product quality test results of different processes

[0075]

[0076] From the data analysis in Table 2, we can see that:

[0077] Comparison between Comparative Example 1 and Comparative Example 2 shows that although 7-AMCA was prepared using different principles and raw materials, the lactone content of the by-product is as high as 11.53-13.72% compared to the present invention.

[0078] This is because the strong base effect of sodium methoxide in Comparative Example 1 easily causes local over-alkalinity, thereby forming a large amount of lactone and causing β-lactam ring opening, which makes the product purity very low and uncontrollable in industrial mass production;

[0079] In Comparative Example 2, the participation of methanesulfonic acid with a strong acidity in the reaction not only increases the content of the by-product lactone, but also easily causes corrosion of workshop equipment, making it difficult to be suitable for large-scale production.

[0080] In order to more intuitively demonstrate the process advantages of the present invention, the synthesis method of the present invention using the cefpodoxime axetil intermediate 7-AMCA is compared with the method using the same process using equivalent replacement.

[0081] Comparative Example 3:

[0082] The preparation method is the same as that of Example 1, except that no base catalyst is added during the preparation of this comparative example;

[0083] Comparative Example 4:

[0084] The preparation method is the same as that of Example 1, except that in the preparation process of this comparative example, the added alkaline catalyst is replaced with a conventional alkaline catalyst, pyridine;

[0085] Comparative Example 5:

[0086] The preparation method is the same as that of Example 1, except that in the preparation process of this comparative example, the added alkaline catalyst is replaced with a conventional alkaline catalyst, triethylamine;

[0087] Comparative Example 6:

[0088] The preparation method is the same as that of Example 1, except that in the preparation process of this comparative example, the base catalyst is replaced by a conventional base catalyst, N,N-dimethylaniline;

[0089] Table 3: Effects of different comparative ratios of alkaline catalysts on product quality

[0090] raw material Polar solvent liquid organic solvents base catalyst Byproduct lactone Molar yield purity Example 1 D-7ACA Sulfolane Ethyl acetate Cesium acetate 0.13％ 85.1％ 97.8％ Comparative Example 3 D-7ACA Sulfolane Ethyl acetate - 15.63％ 71.2％ 76.36％ Comparative Example 4 D-7ACA Sulfolane Ethyl acetate Pyridine 16.55％ 68.5％ 74.74％ Comparative Example 5 D-7ACA Sulfolane Ethyl acetate Triethylamine 11.94％ 69.3％ 76.13％ Comparative Example 6 D-7ACA Sulfolane Ethyl acetate N,N-Dimethylaniline 18.67％ 70.5％ 73.86％

[0091] From the data analysis in Table 3, we can see that:

[0092] Compared with Example 1 and Comparative Example 3, no alkaline catalyst was added, resulting in a decrease in yield and purity, especially a sudden increase in the by-product lactone from 0.13% to 15.63%;

[0093] Compared with Example 1 and Comparative Example 3, the other alkaline catalysts in Comparative Examples 4-6 do not have a good inhibitory effect on the production of by-product lactone compared to cesium acetate or cesium formate, and the by-product lactone is not directly caused by the change in alkalinity.

[0094] In order to more intuitively demonstrate the process advantages of the present invention, the synthesis method of the present invention using the cefpodoxime axetil intermediate 7-AMCA is compared with the method using the same process using equivalent replacement.

[0095] Comparative Example 7:

[0096] The preparation method is the same as that of Example 1, except that in the preparation process of this comparative example, after the iodination reaction in step 3, the base catalyst is removed from the system by manual intervention; specifically:

[0097] (1) Dissolving the starting material D-7ACA in a polar solvent to obtain a D-7ACA polar solvent solution;

[0098] (2) adding an alkaline catalyst to the obtained D-7ACA polar solvent solution;

[0099] (3) controlling the reaction temperature at -30 to 50°C, adding elemental iodine to the reaction solution, reacting for 30 to 60 minutes, and then separating the base catalyst by filtration or centrifugation;

[0100] (4) The reaction temperature is controlled at -30 to 50°C, methanol is added to the above reaction solution, and the reaction time is 30 to 120 minutes to obtain a polar solvent solution containing 7-AMCA.

[0101] Comparative Example 8:

[0102] The preparation method is the same as that of Example 7, except that in the preparation process of this comparative example, after the iodination reaction in step 3, the base catalyst is removed from the system by manual intervention, and then a conventional base catalyst, triethylamine, is added.

[0103] Specifically:

[0104] (1) Dissolving the starting material D-7ACA in a polar solvent to obtain a D-7ACA polar solvent solution;

[0105] (2) adding an alkaline catalyst to the obtained D-7ACA polar solvent solution;

[0106] (3) The reaction temperature is controlled at -30 to 50°C, and elemental iodine is added to the above reaction solution. After the reaction time is 30 to 60 minutes, the base catalyst is separated by filtration or centrifugation, and an equal amount of triethylamine is added;

[0107] (4) The reaction temperature is controlled at -30 to 50°C, methanol is added to the above reaction solution, and the reaction time is 30 to 120 minutes to obtain a polar solvent solution containing 7-AMCA.

[0108] Table 4: Analysis of alkaline catalyst for 7-AMCA dual catalytic test data

[0109] raw material Iodination reaction base catalyst Methylation reaction base catalyst Molar yield purity Example 1 D-7ACA Sulfolane Cesium acetate Ethyl acetate Cesium acetate 85.1％ 97.8％ Comparative Example 7 D-7ACA Sulfolane Cesium acetate Ethyl acetate - 60.5％ 72.81％ Comparative Example 8 D-7ACA Sulfolane Cesium acetate Ethyl acetate Triethylamine 66.3％ 73.19％

[0110] From the data analysis in Table 4, we can see that:

[0111] The difference between Example 1 and Comparative Example 7 is that after the iodination reaction in step 3, the base catalyst is manually intervened to remove the base catalyst from the system, so that cesium acetate cannot play the role of a dual catalyst in the subsequent methylation reaction, thereby achieving the effect of promoting the reaction of 7-AMCA and avoiding the occurrence of side reactions as in the present invention;

[0112] The difference between Example 1 and Comparative Example 7 is that after the iodination reaction in step 3, the alkaline catalyst is removed from the system by manual intervention, and triethylamine is artificially added as an alkaline catalyst. After testing, it can be seen that there is no substantial difference from Comparative Example 7 despite the addition of the alkaline catalyst.

[0113] Therefore, the present invention uses cesium acetate or cesium formate as a base catalyst, creatively playing the role of a dual catalyst in the iodination and methylation reactions, greatly promoting the reaction of 7-AMCA and avoiding the generation of side reactions.

[0114] In summary: the invention uses cesium acetate or cesium formate as a base catalyst to carry out the methylation reaction, avoiding the use of reagents such as boron trifluoride and methanesulfonic acid, which can effectively reduce the risk factor and facilitate operation. The reaction reagents and solvents used in the present invention are non-highly toxic and the harm to the environment and the human body is almost negligible. The molar yield of this process can reach 85% or more, the product purity is 97.5% or more, and the by-product lactone is controlled below 0.3%.

[0115] This invention uses cesium acetate or cesium formate as a base catalyst, creatively playing the role of a dual catalyst in the iodination and methylation reactions, greatly promoting the reaction of 7-AMCA and avoiding the occurrence of side reactions.

Claims

1. A method for synthesizing 7-AMCA, an intermediate of cefpodoxime axetil, characterized in that: include: (1) Dissolving the starting material D-7ACA in a polar solvent to obtain a D-7ACA polar solvent solution; (2) adding a base catalyst to the obtained D-7ACA polar solvent solution, wherein the base catalyst is cesium acetate or cesium formate or a mixture of the two; (3) The reaction temperature is controlled at -30~50℃, and elemental iodine is added to the above reaction solution. The reaction time is 30~60min; (4) The reaction temperature is controlled at -30~50°C, methanol is added to the above reaction solution, and the reaction time is 30~120 min to obtain a polar solvent solution containing 7-AMCA.

2. The method for synthesizing the cefpodoxime proxetil intermediate 7-AMCA according to claim 1, characterized in that The molar ratio of the D-7ACA to the base catalyst is 1:(1.3-4.0).

3. The method for synthesizing the cefpodoxime proxetil intermediate 7-AMCA according to claim 1, characterized in that The polar solvent liquid is sulfone, ether or ester or a mixture thereof.

4. The method for synthesizing the cefpodoxime proxetil intermediate 7-AMCA according to claim 1, characterized in that The molar ratio of the D-7ACA to elemental iodine is 1:(1.2-3.0).

5. The method for synthesizing the cefpodoxime proxetil intermediate 7-AMCA according to claim 1, characterized in that The molar ratio of D-7ACA to methanol is 1:(2.5-4.5).

6. The method for synthesizing the cefpodoxime proxetil intermediate 7-AMCA according to claim 1, wherein: The polar solvent solution of 7-AMCA is added to a mixture of water and an organic solvent at 0-5°C, and the mixture is extracted in layers. The aqueous phase is taken, and the pH is adjusted to 2.0-3.0 with an acid solution. The 7-AMCA is then filtered and dried to obtain the 7-AMCA.

7. The method for synthesizing the cefpodoxime proxetil intermediate 7-AMCA according to claim 6, characterized in that The organic solvent is dichloromethane, ethyl acetate or toluene.

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