Preparation method of [2-(6-chloropyrimidine-4-oxy)phenyl]-3,3-dimethoxypropionic acid methyl ester

Abstract

The present invention relates to the field of pesticides, and discloses a method for preparing [2-(6-chloropyrimidine-4-oxygen)phenyl]-3,3-dimethoxypropionic acid methyl ester, the method comprising: 1) in the presence of a solvent, 3-(α-methoxy)-methylenebenzofuran-2(3H)-one is subjected to a first contact reaction with a base to obtain a mixed solution; 2) in the presence of a catalyst and a carbonate, the mixed solution is subjected to a second contact reaction with 4,6-dichloropyrimidine, wherein the base is one or more of an alkali metal hydroxide, an alkali metal alcoholate and an alkali metal salt. According to the method of the present invention, it has fewer impurities during the reaction process, has high selectivity and conversion rate, has a high yield, and the recovered solvent can be applied, no waste water is generated, and is suitable for industrial production.

Description

Technical Field

[0001] The invention relates to the field of pesticides, and in particular to a method for preparing methyl [2-(6-chloropyrimidine-4-oxy)phenyl]-3,3-dimethoxypropionate. Background Art

[0002] Methyl [2-(6-chloropyrimidine-4-oxy)phenyl]-3,3-dimethoxypropionate is an important intermediate of the new highly effective, broad-spectrum, systemic fungicide azoxystrobin, and its structure is shown below.

[0003]

[0004] At present, there are two main methods for the synthesis of [2-(6-chloropyrimidin-4-oxy)phenyl]-3,3-dimethoxypropionic acid methyl ester. The first method is a "one-pot method" in which 3-(α-methoxy)-methylenebenzofuran-2(3H)-one and 4,6-dichloropyrimidine are reacted with a catalyst and a strong base is added for etherification to obtain [2-(6-chloropyrimidin-4-oxy)phenyl]-3,3-dimethoxypropionic acid methyl ester. The second method is to use 3-(α-methoxy)-methylenebenzofuran-2(3H)-one and sodium alcohol to first carry out ester exchange and addition, and then acidify to obtain 3,3-dimethoxy-2-(2-hydroxyphenyl)propionic acid methyl ester, and then wash with water, extract with dichloromethane, dry and remove dichloromethane; then use the obtained 3,3-dimethoxy-2-(2-hydroxyphenyl)propionic acid methyl ester and 4,6-dichloropyrimidine in the presence of a catalyst to obtain [2-(6-chloropyrimidine-4-oxy)phenyl]-3,3-dimethoxypropionic acid methyl ester. Summary of the invention

[0005] After in-depth research, the inventors of the present invention found that in the above-mentioned first synthesis method, the preparation process needs to go through three processes of ester exchange, addition and etherification. Since 3-(α-methoxy)-methylenebenzofuran-2(3H)-one and 4,6-dichloropyrimidine exist in the same system, the two have a competitive reaction with the strong base. Therefore, more 4-methoxy-6-chloropyrimidine impurities will be produced in the reaction, and a higher amount of double-bonded impurities 2,2'-((pyrimidine-4,6-diylbis(oxy))bis(2,1-phenylene))(2E,2'E)-bis(3-methoxypropionate) will be generated, which ultimately leads to low yield, high DCP consumption and high cost.

[0006] The above-mentioned second synthesis method has the problem of low selectivity, and the synthesis method needs to be carried out at -20°C when acidifying 3,3-dimethoxy-2-(2-hydroxyphenyl)propionic acid methyl ester. The yield of 3,3-dimethoxy-2-(2-hydroxyphenyl)propionic acid methyl ester obtained after acidification is not high, and a large amount of waste water is generated, which is very unfavorable for industrial production.

[0007] The purpose of the present invention is to overcome the above-mentioned problems existing in the prior art and to provide a method for preparing [2-(6-chloropyrimidine-4-oxy)phenyl]-3,3-dimethoxypropionic acid methyl ester using 3-(α-methoxy)-methylenebenzofuran-2(3H)-one (a compound with a structure shown in formula (1)) as a raw material. The method has fewer impurities during the reaction process, high selectivity and conversion rate, high yield, and the recovered solvent can be reused without generating waste water, and is suitable for industrial production.

[0008] In order to achieve the above object, the present invention provides a method for preparing methyl [2-(6-chloropyrimidine-4-oxy)phenyl]-3,3-dimethoxypropionate, wherein the method comprises the following steps:

[0009] 1) in the presence of a solvent, subjecting the compound having the structure represented by formula (1) to a first contact reaction with a base to obtain a mixed solution containing the compound having the structure represented by formula (2);

[0010] 2) In the presence of a catalyst and a carbonate, a mixed solution containing a compound of formula (2) is subjected to a second contact reaction with 4,6-dichloropyrimidine.

[0011]

[0012] Wherein, the base is one or more of alkali metal hydroxide, alkali metal alcoholate and alkali metal salt; in formula (2), X is an alkali metal.

[0013] Preferably, in step 1), the molar ratio of the compound of the structure represented by formula (1) to the base is 1:0.8-3; more preferably, the molar ratio of the compound of the structure represented by formula (1) to the base is 1:0.9-1.5.

[0014] Preferably, in step 1), X is sodium and / or potassium.

[0015] Preferably, the base is one or more of sodium tert-butoxide, potassium tert-butoxide, sodium methoxide, potassium methoxide, sodium hydroxide, potassium hydroxide, potassium carbonate and sodium carbonate; more preferably, the base is one or more of sodium tert-butoxide, sodium methoxide and sodium hydroxide.

[0016] Preferably, in step 1), the molar ratio of the compound having the structure represented by formula (1) to the solvent is 1:2-50.

[0017] Preferably, the solvent is one or more of methanol, toluene and dimethylformamide; more preferably, the solvent is methanol.

[0018] Preferably, in step 1), the conditions of the first contact reaction include: the contact reaction temperature is -30 to 30° C., and the contact reaction time is 0.5 to 10 hours.

[0019] Preferably, in step 2), a mixed solution containing the compound having the structure represented by formula (2) is added to a mixture containing 4,6-dichloropyrimidine, a catalyst, a carbonate and an organic solvent to carry out the second contact reaction; more preferably, a mixed solution containing the compound having the structure represented by formula (2) is added dropwise to a mixture containing 4,6-dichloropyrimidine, a catalyst, a carbonate and an organic solvent to carry out the second contact reaction.

[0020] Preferably, the organic solvent is one or more of toluene, dimethylformamide, dimethylacetamide, ethylene glycol dimethyl ether, dimethyl sulfoxide, 4-methyl-2-pentanone, dimethyl carbonate and methyl benzoate.

[0021] Preferably, the amount of the organic solvent used is 2-30 mol relative to 1 mol of 4,6-dichloropyrimidine.

[0022] Preferably, based on 1 mol of the compound of the structure represented by formula (1) in step 1), the amount of the carbonate used is 0.05-1 mol.

[0023] Preferably, the carbonate is one or more of potassium carbonate, sodium carbonate and cesium carbonate.

[0024] Preferably, based on 1 mol of the compound of the structure represented by formula (1) in step 1), the amount of 4,6-dichloropyrimidine used is 0.9-1.4 mol.

[0025] Preferably, based on 1 mol of the compound of the structure represented by formula (1) in step 1), the amount of the catalyst used is 0.001-1 mol.

[0026] Preferably, the catalyst is one or more of 1,4-diazabicyclo[2.2.2]octane, 2-methyl-1,4-diazabicyclo[2.2.2]octane and trimethylamine hydrochloride.

[0027] Preferably, the method further comprises the step of removing the solvent during the second contact reaction.

[0028] Preferably, the removed solvent is used as the solvent in step 1).

[0029] Preferably, the conditions of the second contact reaction include: the contact reaction temperature is 10-100° C., the contact reaction pressure is -0.04 to -0.1 MPa, and the contact reaction time is 0.5 to 10 hours.

[0030] Through the above technical scheme, the present invention provides a method for preparing [2-(6-chloropyrimidine-4-oxy)phenyl]-3,3-dimethoxypropionic acid methyl ester using 3-(α-methoxy)-methylenebenzofuran-2(3H)-one as a raw material. The method has fewer impurities during the reaction process, high selectivity and conversion rate, high yield, and the recovered solvent can be reused without generating wastewater, and is suitable for industrial production. DETAILED DESCRIPTION

[0031] The endpoints and any values ​​of the ranges disclosed in this article are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of each range, the endpoint values ​​of each range and the individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed in this article.

[0032] The present invention provides a method for preparing methyl [2-(6-chloropyrimidine-4-oxy)phenyl]-3,3-dimethoxypropionate, wherein the method comprises the following steps:

[0033] 1) in the presence of a solvent, subjecting the compound having the structure represented by formula (1) to a first contact reaction with a base to obtain a mixed solution containing the compound having the structure represented by formula (2);

[0034] 2) in the presence of a catalyst and a carbonate, subjecting the mixed solution containing the compound having the structure represented by formula (2) to a second contact reaction with 4,6-dichloropyrimidine,

[0035]

[0036] Wherein, the base is one or more of alkali metal hydroxide, alkali metal alcoholate and alkali metal salt; in formula (2), X is an alkali metal.

[0037] According to the present invention, the alkali metal is preferably sodium and / or potassium. The alkali metal salt is preferably a carbonate.

[0038] According to the present invention, preferably, in step 1), the base is one or more of sodium tert-butoxide, potassium tert-butoxide, sodium methoxide, potassium methoxide, sodium hydroxide, potassium hydroxide, potassium carbonate and sodium carbonate; more preferably, the base is one or more of sodium tert-butoxide, sodium methoxide and sodium hydroxide.

[0039] According to the present invention, in step 1), the amount of the base can be selected according to the amount of the compound of the structure shown in formula (1). Specifically, the molar ratio of the compound of the structure shown in formula (1) to the base is 1:0.8-3; preferably, the molar ratio of the compound of the structure shown in formula (1) to the base is 1:0.9-1.5; more preferably, the molar ratio of the compound of the structure shown in formula (1) to the base is 1:0.95-1.3; further preferably, the molar ratio of the compound of the structure shown in formula (1) to the base is 1:1-1.2.

[0040] According to the present invention, the first contact reaction is carried out in the presence of a solvent, and the solvent can dissolve the reaction raw materials and is inert to the reaction raw materials, preferably one or more of methanol, toluene and dimethylformamide, more preferably methanol.

[0041] According to the present invention, there is no particular limitation on the amount of the solvent used, as long as the first contact reaction can be fully carried out. Preferably, in step 1), the molar ratio of the compound with the structure shown in formula (1) to the solvent is 1:2-50; more preferably, the molar ratio of the compound with the structure shown in formula (1) to the solvent is 1:3-20.

[0042] According to the present invention, preferably, in step 1), the conditions of the first contact reaction include: the temperature of the contact reaction is below 30°C, and the time of the contact reaction is more than 0.5 hour; more preferably, the conditions of the first contact reaction include: the temperature of the contact reaction is -30 to 30°C, and the time of the contact reaction is 0.5-10 hours; further preferably, the conditions of the first contact reaction include: the temperature of the contact reaction is -10 to 20°C, and the time of the contact reaction is 1-8 hours; further preferably, the conditions of the first contact reaction include: the temperature of the contact reaction is -5 to 20°C, and the time of the contact reaction is 2-5 hours.

[0043] According to the present invention, the method of the first contact reaction is not particularly limited, as long as the above-mentioned contact conditions are met, and can be various contact methods commonly used in the art. Preferably, the first contact reaction is carried out by dropping the solution of the base into the solution of the compound of the structure represented by formula (1).

[0044] According to the present invention, after the first contact reaction is completed, it can be directly used for the second contact reaction without being processed.

[0045] According to the present invention, in the presence of a catalyst and a carbonate, a mixed solution containing a compound having a structure represented by formula (2) is subjected to a second contact reaction with 4,6-dichloropyrimidine. Preferably, in step 2), the mixed solution containing a compound having a structure represented by formula (2) is added to a mixture containing 4,6-dichloropyrimidine, a catalyst, a carbonate and an organic solvent to carry out the second contact reaction; more preferably, the mixed solution containing a compound having a structure represented by formula (2) is added dropwise to a mixture containing 4,6-dichloropyrimidine, a catalyst, a carbonate and an organic solvent to carry out the second contact reaction.

[0046] The above-mentioned organic solvent can be one or more of toluene, dimethylformamide, dimethylacetamide, ethylene glycol dimethyl ether, dimethyl sulfoxide, 4-methyl-2-pentanone, dimethyl carbonate and methyl benzoate; preferably, the above-mentioned organic solvent is one or more of toluene, dimethyl sulfoxide, dimethylformamide and dimethylacetamide.

[0047] According to the present invention, the amount of the organic solvent can be selected according to the amount of 4,6-dichloropyrimidine. Preferably, the amount of the organic solvent is 2-30 mol relative to 1 mol of 4,6-dichloropyrimidine; more preferably, the amount of the organic solvent is 5-15 mol relative to 1 mol of 4,6-dichloropyrimidine.

[0048] According to the present invention, preferably, the catalyst is one or more of 1,4-diazabicyclo[2.2.2]octane (DABCO), 2-methyl-1,4-diazabicyclo[2.2.2]octane and trimethylamine hydrochloride; more preferably, the catalyst is 1,4-diazabicyclo[2.2.2]octane.

[0049] According to the present invention, after the first contact reaction in step 1) is completed, the reaction product is directly used for the second contact reaction in the next step. Therefore, the amount of 4,6-dichloropyrimidine can be selected according to the compound of the structure represented by formula (1). Preferably, based on 1 mol of the compound of the structure represented by formula (1) in step 1), the amount of 4,6-dichloropyrimidine is 0.9-1.3 mol; more preferably, based on 1 mol of the compound of the structure represented by formula (1) in step 1), the amount of 4,6-dichloropyrimidine is 0.95-1.1 mol; further preferably, based on 1 mol of the compound of the structure represented by formula (1) in step 1), the amount of 4,6-dichloropyrimidine is 1-1.05 mol.

[0050] Similarly, since after the first contact reaction in step 1) is completed, the reaction product is directly used for the next second contact reaction, the amount of the catalyst can be selected according to the compound of the structure represented by formula (1). Preferably, the amount of the catalyst is 0.001-1 mol based on 1 mol of the compound of the structure represented by formula (1) in step 1); more preferably, the amount of the catalyst is 0.001-0.5 mol based on 1 mol of the compound of the structure represented by formula (1) in step 1); further preferably, the amount of the catalyst is 0.01-0.1 mol based on 1 mol of the compound of the structure represented by formula (1) in step 1); further preferably, the amount of the catalyst is 0.01-0.05 mol based on 1 mol of the compound of the structure represented by formula (1) in step 1).

[0051] Similarly, since after the first contact reaction in step 1) is completed, the reaction product is directly used for the second contact reaction in the next step, the amount of the carbonate can be selected according to the compound of the structure shown in formula (1). Preferably, based on 1 mol of the compound of the structure shown in formula (1) in step 1), the amount of the carbonate is 0.1-1 mol; more preferably, based on 1 mol of the compound of the structure shown in formula (1) in step 1), the amount of the carbonate is 0.2-0.5 mol.

[0052] The carbonate may be, for example, one or more of potassium carbonate, sodium carbonate and cesium carbonate, preferably potassium carbonate and / or sodium carbonate.

[0053] According to the present invention, preferably, the method further comprises the step of removing the solvent during the second contact reaction. As a method for removing the solvent during the second contact reaction, for example, the second contact reaction can be carried out while removing the solvent by distillation during the second contact reaction.

[0054] In the present invention, the removed solvent is preferably used as the solvent in step 1).

[0055] According to the present invention, preferably, the conditions of the second contact reaction include: the temperature of the contact reaction is 10-100°C, the pressure of the contact reaction is -0.04 to -0.1 MPa, and the time of the contact reaction is 0.5 to 10 hours; more preferably, the conditions of the second contact reaction include: the temperature of the contact reaction is 15-95°C, the pressure of the contact reaction is -0.05 to -0.1 MPa, and the time of the contact reaction is 6 to 9 hours. Here, the time of the contact reaction includes the feeding time.

[0056] According to the present invention, after the second contact reaction is completed, a filtrate with a low impurity content can be obtained by solid-liquid separation (e.g., filtration) of the reaction product. When preparing azoxystrobin, the filtrate solvent only needs to be removed (e.g., by distillation) before use without further refining treatment. Of course, the filtrate can also be refined by various refining methods in the art. For example, after the filtrate solvent is removed, a solvent (e.g., methanol) can be used for recrystallization to obtain high-purity [2-(6-chloropyrimidine-4-oxy)phenyl]-3,3-dimethoxypropionic acid methyl ester.

[0057] Specifically, the present invention uses 3-(α-methoxy)-methylenebenzofuran-2(3H)-one as a raw material to prepare [2-(6-chloropyrimidine-4-oxy)phenyl]-3,3-dimethoxypropionic acid methyl ester. The method has fewer impurities during the reaction process, has high selectivity and conversion rate, and the solvent can be directly applied without generating wastewater. Moreover, after the first contact reaction, the reaction product can be directly used for the second contact reaction, and after the second contact reaction, the reaction product obtained has less impurity content and a high yield of the target product. It only needs to remove the solvent to be used for the preparation of azoxystrobin, which greatly simplifies the process.

[0058] The present invention will be described in detail below by way of examples, but the present invention is not limited to the following examples.

[0059] In the following examples, the determination conditions of HPLC are as follows:

[0060] Instrument: Agilent 1260 liquid chromatograph

[0061] Detector: UV detector

[0062] Detection wavelength: 215nm

[0063] Column: RX-C18 (250mm×4.6mm, 5um)

[0064] Elution phase: acetonitrile / PH2-3 phosphoric acid water

[0065] Flow rate: 1ml / min

[0066] Injection volume: 1.0 μl

[0067] Example 1

[0068] 1) Ring opening: 35.9 g (0.2 mol, 98 wt % content) of the compound of formula (1) (3-(α-methoxy)-methylenebenzofuran-2(3H)-one) was placed in a 500 ml four-necked bottle, 100 ml of methanol was added to dissolve, the temperature was lowered to 20° C., 43.1 g (0.24 mol, 30 wt % content) of sodium methoxide methanol solution was added dropwise at a temperature below 20° C., and the mixture was dripped over within 1 hour. After the dripping was completed, the mixture was stirred for 2 hours at the same temperature to obtain a methanol solution containing the compound of formula (2) (LCMS: M / Z=262 (M+Na) + );

[0069] 2) Condensation: In another 500ml four-necked bottle, 31.7g (0.21mol, 98wt%) of 4,6-dichloropyrimidine, 14.1g (0.1mol, 98wt%) of potassium carbonate, 0.4g of catalyst DABCO, and 200ml of toluene were added, the temperature was raised to 60°C, the temperature was kept at 60-65°C, and the vacuum was -0.05MPa. The methanol solution prepared above was added dropwise, and the methanol was distilled out of the reaction system while adding dropwise. After the addition was completed, the temperature was kept at 60-70°C for 3h, and then the inorganic salt was removed by filtration. The filtrate was sampled for HPLC quantification, and the yield was 92% (calculated based on 3-(α-methoxy)-methylenebenzofuran-2(3H)-one). After the solvent was distilled off, it was recrystallized with methanol to obtain [2-(6-chloropyrimidine-4-oxy)phenyl]-3,3-dimethoxypropionic acid methyl ester (LCMS: M / Z=353 (M+H) + ), with a purity of 97% by weight.

[0070] Product NMR data: HNMR (CDCl3): δ8.6 (1H.s); 7.7-7.1 (4H.m); 6.9 (1H.s); 5.0 (1H.d); 4.2 (1H.d); 3.55 (3H.s); 3.4 (3H.s); 3.2 (3H.s) ppm.

[0071] Example 2

[0072] 1) Ring opening: 35.9 g (0.2 mol, 98 wt%) of 3-(α-methoxy)-methylenebenzofuran-2(3H)-one was added to a 500 ml four-necked bottle, and 100 ml of methanol was added. The temperature was lowered to -5°C, and 41.1 g (0.22 mol, 30 wt%) of a methanol solution of potassium hydroxide was added dropwise at -5 to 5°C. The mixture was added dropwise over 2 h, and the mixture was stirred at 0°C for 2 h to obtain a methanol solution of a compound having the structure represented by formula (2).

[0073] 2) Condensation: In another 500ml four-necked bottle, 31.7g (0.21mol, 98wt%) of 4,6-dichloropyrimidine, 4.4g (0.04mol, 98wt%) of sodium carbonate, 0.8g of DABCO and 200ml of DMSO were added, the temperature was raised to 80°C, the temperature was kept at 80-90°C, vacuum was -0.095MPa, the methanol solution prepared above was added dropwise, and the methanol was distilled out of the reaction system while adding dropwise. After the addition was completed, the temperature was kept at 80-90°C for 4h, and then the inorganic salt was removed by filtration. The filtrate was sampled for HPLC quantitative analysis, and the yield was 89% (calculated based on 3-(α-methoxy)-methylenebenzofuran-2(3H)-one). After the solvent was distilled off, it was recrystallized with methanol to obtain [2-(6-chloropyrimidine-4-oxy)phenyl]-3,3-dimethoxypropionic acid methyl ester with a purity of 96wt%.

[0074] Example 3

[0075] 1) Ring opening: 35.9 g (0.2 mol, 98 wt %) of the compound of formula (1) was placed in a 500 ml four-necked bottle, 100 ml of methanol was added to dissolve, the temperature was lowered to 20° C., 34.2 g (0.19 mol, 30 wt %) of sodium methoxide methanol solution was added dropwise at a temperature below 20° C., the mixture was dripped over 1 hour, and after the dripping was completed, the mixture was kept warm and stirred for 3 hours to obtain a methanol solution containing the compound of formula (2);

[0076] 2) Condensation: In another 500ml four-necked bottle, 31.7g (0.21mol, 98wt%) of 4,6-dichloropyrimidine, 11.26g (0.08mol, 98wt%) of potassium carbonate, 1.14g of catalyst DABCO and 200ml of toluene were added, the temperature was raised to 20°C, kept at 20-30°C, vacuumed to -0.085MPa, the methanol solution prepared above was added dropwise, and the methanol was distilled out of the reaction system while adding dropwise, the dropping was completed after 4h, the temperature was kept at 25-30°C for 2h, and then the inorganic salt was removed by filtration, and the filtrate was sampled for HPLC quantitative analysis, the yield was 90% (calculated based on 3-(α-methoxy)-methylenebenzofuran-2(3H)-one), the solvent was distilled off and recrystallized with methanol to obtain [2-(6-chloropyrimidine-4-oxy)phenyl]-3,3-dimethoxypropionic acid methyl ester with a purity of 95wt%.

[0077] Example 4

[0078] The method of Example 1 was followed, except that methanol was not distilled off during the addition of the methanol solution. Other than that, methyl [2-(6-chloropyrimidin-4-oxy)phenyl]-3,3-dimethoxypropionate was obtained in the same manner as Example 1 with a yield of 50% and a purity of 55% by weight.

[0079] The preferred embodiments of the present invention are described in detail above, but the present invention is not limited thereto. Within the technical concept of the present invention, the technical solution of the present invention can be subjected to a variety of simple modifications, including the combination of various technical features in any other suitable manner, and these simple modifications and combinations should also be regarded as the contents disclosed by the present invention and belong to the protection scope of the present invention.

Claims

1. A method for preparing methyl [2-(6-chloropyrimidine-4-oxy)phenyl]-3,3-dimethoxypropionate, characterized in that: The Method The following steps are included: 1) in the presence of a solvent, subjecting the compound of the structure represented by formula (1) to a first contact reaction with a base to obtain a mixed solution containing the compound of the structure represented by formula (2); 2) adding the mixed solution containing the compound of formula (2) to a mixture containing 4,6-dichloropyrimidine, a catalyst, a carbonate and an organic solvent to carry out a second contact reaction, Formula (1) Formula (2), In formula (2), X is sodium or potassium, The solvent is methanol, and the base is one or more of sodium methoxide, potassium methoxide, sodium hydroxide and potassium hydroxide. The organic solvent is one or more of toluene, dimethylformamide, dimethylacetamide, ethylene glycol dimethyl ether, dimethyl sulfoxide, 4-methyl-2-pentanone, dimethyl carbonate and methyl benzoate. The carbonate is one or more of potassium carbonate, sodium carbonate and cesium carbonate, The catalyst is one or more of 1,4-diazabicyclo[2.2.2]octane, 2-methyl-1,4-diazabicyclo[2.2.2]octane and trimethylamine hydrochloride, Based on 1 mol of the compound of formula (1) in step 1), the amount of 4,6-dichloropyrimidine used is 0.95-1.1 mol. The method further comprises the step of removing the solvent during the second contact reaction. The structure of the [2-(6-chloropyrimidine-4-oxy)phenyl]-3,3-dimethoxypropionic acid methyl ester is shown in formula (3), Formula (3).

2. The method according to claim 1, wherein: In step 1), the molar ratio of the compound having the structure represented by formula (1) to the base is 1:0.8-3.

3. The method according to claim 2, wherein: In step 1), the molar ratio of the compound having the structure represented by formula (1) to the base is 1:0.9-1.

5.

4. The method according to any one of claims 1 to 3, wherein: In step 1), the molar ratio of the compound having the structure represented by formula (1) to the solvent is 1:2-50.

5. The method according to any one of claims 1 to 3, wherein: In step 1), the conditions of the first contact reaction include: the contact reaction temperature is -30 to 30° C., and the contact reaction time is 0.5 to 10 hours.

6. The method according to claim 1, wherein: The amount of the organic solvent used is 2-30 mol relative to 1 mol of 4,6-dichloropyrimidine.

7. The method according to any one of claims 1 to 3, wherein: Based on 1 mol of the compound of the structure represented by formula (1) in step 1), the amount of the carbonate used is 0.05-1 mol.

8. The method according to any one of claims 1 to 3, wherein: Based on 1 mol of the compound of the structure represented by formula (1) in step 1), the amount of the catalyst used is 0.001-1 mol.

9. The method according to any one of claims 1 to 3, wherein: The removed solvent is used as the solvent in step 1).

10. The method according to any one of claims 1 to 3, wherein: The conditions of the second contact reaction include: the temperature of the contact reaction is 10-100° C., the pressure of the contact reaction is -0.04-0.1 MPa, and the time of the contact reaction is 0.5-10 hours.

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