Process method for preparing fluopyram key intermediate

Abstract

The invention discloses a process method for preparing a fluopyram key intermediate. The key intermediate is [3-chloro-5-(trifluoromethyl) pyridine-2-yl] ({[2-(trifluoromethyl) benzoyl] amino} methyl) dimethyl malonate, and the process method comprises the following steps: in the presence of a solvent 1, carrying out a reaction on a compound 2-[3-chloro-5-(trifluoromethyl) pyridyl] dimethyl malonate potassium salt and a compound 1-D in a reaction container, and distilling and recovering the solvent 1 to obtain the intermediate compound. Wherein the solvent 1 is selected from acetic ester solvents with the boiling point range of 40-110 DEG C at normal temperature and normal pressure. The process method is simple and convenient, the total yield is high, the solvent is easy to recover, and the product purity is high; the intermediate does not need purification post-treatment, can be directly used for synthesis of fluopyram, can be amplified, and is beneficial to cost reduction, efficiency improvement and commercial mass production.

Description

Technical Field

[0001] The invention relates to a process for preparing a key intermediate of fluopyram, and in particular to a process for preparing dimethyl [3-chloro-5-(trifluoromethyl)pyridin-2-yl]({[2-(trifluoroformyl)benzoyl]amino}methyl)malonate, belonging to the technical field of pesticide chemical industry. Background Art

[0002] Fluopyram is a benzamide fungicide discovered and developed by Bayer and is a succinate dehydrogenase inhibitor (SDHI). Its chemical name is: N-{2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]ethyl}-2-(trifluoromethyl)benzamide; molecular formula: C 16 H 11 CIF 6 N 2 O; relative molecular mass: 396.76; CAS registration number: 658066-35-4. Fluopyram is an excellent fungicide and nematicide. It has been registered and marketed in more than 60 countries and regions around the world and used for more than 70 crops. Fluopyram has low toxicity and is environmentally friendly.

[0003] [3-chloro-5-(trifluoromethyl)pyridin-2-yl]({[2-(trifluoroformyl)benzoyl]amino}methyl)malonate, molecular formula: C 20 H 15 CIF 6 N 2 O 5 ; Relative molecular mass: 512.79; CAS registration number: 895525-76-5, it is a key intermediate in the synthesis of fluopyram, referred to as intermediate compound 1-G, and its chemical structure is as follows:

[0004]

[0005] At present, in actual production, the preparation of the key intermediate of fluopyram [3-chloro-5-(trifluoromethyl)pyridin-2-yl] ({[2-(trifluoroformyl)benzoyl]amino}methyl) dimethyl malonate (intermediate compound 1-G) has the problems of complicated process, low yield, difficult solvent recovery, low product purity, etc. In order to improve market competitiveness, it is necessary to find a preparation process with simple process, high total yield, easy solvent recovery and high product purity. At present, the process methods for preparing the intermediate compound 1-G mainly include the following:

[0006] Route 1: Patent CN108822024 discloses a method for synthesizing an intermediate compound 1-G, including: step 4, adding formamide as a solvent to the hydroxymethylated white solid, heating, dripping acetic anhydride, continuing the reaction after the dripping, cooling to 25°C, and obtaining an esterification product; step 5, adding 5-trifluoromethyl-2-malonic acid dimethyl ester-3-chloropyridine to the esterification product, heating and keeping the reaction for 6 hours, cooling to 25°C, and obtaining a condensation product, which is the intermediate compound 1-G. The total yield of the three-step reaction of step 4, step 5, and step 6 in this route is about 79.3% calculated based on the hydroxymethylated product. In step 4 and step 5, formamide is used as a solvent, and the formamide solvent is difficult to recover. The purity of the intermediate compound 1-G is not reported in this patent.

[0007] Route 2: Patent WO2018114484 discloses that o-trifluoromethylbenzoic acid is used as a raw material, and intermediate B5 is prepared by acylation, amination, hydroxymethylation, and esterification; 2,3-dichloro-5-trifluoromethylpyridine and diethyl malonate are used as raw materials for condensation to prepare intermediate B1, and then intermediate B5 and intermediate B1 are condensed to prepare intermediate B6, which is intermediate compound 1-G, and finally hydrolyzed and decarboxylated to obtain fluopyram. In this process route, intermediate B5 and intermediate B1 are condensed at 80°C, and N,N-dimethylacetamide and acetic acid are used as solvents. The conditions for distillation and recovery of N,N-dimethylacetamide are relatively harsh during the actual amplification reaction, and the mixed solvent is also difficult to separate and recover, which is not conducive to large-scale production. After the intermediate B6 mixture is diluted with water, methyl tert-butyl ether (MTBE) is used for extraction, and MTBE needs to be distilled to remove MTBE later. Intermediate B6 needs to be extracted and purified, and the process is relatively cumbersome. The yield of the last four steps is about 86.5%.

[0008]

[0009] Route 3: Patent CN117003691A, patent name: A method for preparing fluopyram. Use 2-[3-chloro-5-(trifluoromethyl)pyridinyl]malonate dimethyl potassium salt, that is, intermediate 1, and N-(chloromethyl)-2-trifluoromethylbenzamide, that is, intermediate 2, in the presence of solvent 3 to react, and after separation, intermediate 3, that is, intermediate compound 1-G, is obtained; then intermediate 3 is neutralized with water in solvent 4, and the base continues to react, and finally the product fluopyram is separated. This route is relatively long, and after the reaction of step 3 is completed, it also includes post-treatment steps: recovering the solvent under reduced pressure, adding an organic solvent and water to the residue, separating the liquids after extraction, washing the organic phase with water, concentrating under reduced pressure to obtain a crude product, and recrystallizing to obtain the intermediate compound 1-G. The process is relatively complicated; at the same time, solvent 3 is N,N-dimethylacetamide and / or dimethyl sulfoxide, which has a high boiling point (over 150°C), is difficult to recover, and has a high recovery cost; the total yield of the two-step reaction of step 4 and step 5 (the last two steps) is about 76.1-79.2%, and the total yield of the route is about 66.9-71.4%.

[0010]

[0011] Route 4: Patent CN116854629A, patent name: A method for preparing fluopyram. 2-[3-chloro-5-(trifluoromethyl)pyridinyl]malonate dimethyl potassium salt, i.e., intermediate 1, and N-(chloromethyl)-2-trifluoromethylbenzamide, i.e., intermediate 3, are reacted in the presence of solvent 4, and intermediate 4, i.e., intermediate compound 1-G, is obtained after separation; then, intermediate 4 is neutralized with water in solvent 5, and the base is further reacted, and finally, the product fluopyram is separated. This route is relatively long, and after the reaction of step 4 is completed, it also includes post-treatment steps: recovering the solvent under reduced pressure, adding an organic solvent and water to the residue, separating the liquids after extraction, washing the organic phase with water, concentrating under reduced pressure to obtain a crude product, and recrystallizing to obtain the intermediate compound 1-G, and the process is relatively complicated; at the same time, solvent 4 is N,N-dimethylacetamide and / or dimethyl sulfoxide, which has a high boiling point (over 150°C), is difficult to recover, and has a high recovery cost; at the same time, the total yield of the two-step reaction of step 4 and step 5 (the last two steps) is about 80.5-80.9%, and the total yield of the route is about 68.2-70.9%.

[0012]

[0013] Based on the above reasons, there is an urgent need for a process for preparing the key intermediate [3-chloro-5-(trifluoromethyl)pyridin-2-yl]({[2-(trifluoroformyl)benzoyl]amino}methyl)malonate (intermediate compound 1-G) of fluopyram, so as to solve the problems of complicated process, low yield, difficult solvent recovery, low product purity, etc. in the preparation of the intermediate compound, and improve market competitiveness. Summary of the invention

[0014] The purpose of the present invention is to provide a method for preparing a key intermediate of fluopyram (intermediate compound 1-G) with simple process, high total yield, easy solvent recovery and high product purity in view of the shortcomings of the prior art.

[0015] In order to achieve the above object, the present invention provides a process for preparing a key intermediate of fluopyram, comprising the following steps: in the presence of solvent 1, compound 1-F, i.e., 2-[3-chloro-5-(trifluoromethyl)pyridinyl]malonate dimethyl ester potassium salt, and compound 1-D are reacted in a reaction container, and after the reaction, solvent 1 is distilled and recovered to obtain an intermediate compound 1-G; the reaction equation is as follows:

[0016]

[0017] Wherein, the compound 1-D is selected from N-(acetoxymethyl)-2-trifluoromethylbenzamide (i.e., compound 1-D-1) and / or N-(chloromethyl)-2-trifluoromethylbenzamide (i.e., compound 1-D-2); the solvent 1 is selected from an acetate solvent having a boiling point range of 40-110°C at normal temperature and pressure.

[0018] Preferably, the solvent 1 is selected from a combination of one or more of methyl acetate, ethyl acetate and isopropyl acetate.

[0019] Preferably, the molar ratio of the compound 1-F to the compound 1-D is 1:0.95-1.10; the mass ratio of the compound 1-F to the solvent 1 is 1:5.0-11.0.

[0020] Preferably, in the steps, the feeding temperature is 40-55°C; the reaction temperature is 40-65°C; and the reaction time is 3-6 hours.

[0021] Preferably, the distillation temperature in the distillation recovery solvent 1 is 40-100° C., and the vacuum degree of distillation is -0.070 to -0.098 MPa.

[0022] Preferably, the compound 1-F, i.e., 2-[3-chloro-5-(trifluoromethyl)pyridinyl]malonate dimethyl ester potassium salt, has a purity of ≥97.0% and a mass content of ≥93.0%. In the present invention, the compound 1-F can be prepared by a literature method (e.g., the method described in patent CN116854629A but not limited to this method), or a commercially available product can be selected.

[0023] Preferably, in the above steps, after the solvent 1 is distilled and recovered, the residual amount of the solvent 1 is ≤3%, and the purity of the intermediate compound 1-G is ≥95.8%.

[0024] The present invention also verifies through experiments that the intermediate compound 1-G obtained by the process method has a high purity of ≥95.8%, and a small amount of by-products and a small amount of solvent 1 therein can be used directly without purification, with little impact on subsequent reactions, and can be converted into a fungicide such as fluopyram after further reaction.

[0025] Compared with the prior art, the present invention has the following beneficial effects:

[0026] 1. The present invention provides a process for preparing an intermediate compound 1-G using compound 1-F, i.e., 2-[3-chloro-5-(trifluoromethyl)pyridinyl]malonate dimethyl potassium salt and compound 1-D as raw materials in a suitable acetate solvent; the intermediate compound 1-G prepared by the process has a high purity of ≥95.8%, and can reach up to 97.8%, and does not require additional purification steps. The process is simple and suitable for large-scale production;

[0027] 2. In the present invention, acetate solvents such as methyl acetate, ethyl acetate, isopropyl acetate, etc. with a boiling point range of 40-110°C at normal temperature and pressure are used. These acetate solvents are more suitable for the process method than other solvents such as N,N-dimethylacetamide, N-methylpyrrolidone, 1,2-dichloroethane, formamide, acetic acid, etc.; the use of these acetate solvents in the process method has at least the following advantages: first, the obtained product intermediate compound 1-G has high purity and few impurities; secondly, these acetate solvents are easy to recover, the conditions are mild, the solvent recovery rate is high, and basically no new impurities are generated during the solvent recovery process; the process method In addition to the characteristics of simple process, the method also has the characteristics of high total yield; the molar yield of the intermediate compound 1-G obtained by the process is ≥95.5%, and can reach up to 97.7% (calculated as 2-[3-chloro-5-(trifluoromethyl)pyridinyl]malonate dimethyl ester potassium salt); the crude intermediate compound 1-G obtained by the process, a small amount of by-products and a small amount of solvent 1 therein, can be used directly without purification, and have little effect on subsequent reactions; the simplification of the production process is conducive to reducing the manufacturing cost; the improvement of the total yield is conducive to reducing the cost of raw materials, reducing costs and increasing efficiency, and is conducive to large-scale commercial production;

[0028] 3. Compound 1-F, i.e., potassium salt of dimethyl 2-[3-chloro-5-(trifluoromethyl)pyridinyl]malonate, generally has good solubility in highly polar solvents, and solvents such as N,N-dimethylacetamide, N-methylpyrrolidone, formamide, acetic acid, etc. are generally preferred for the reaction. After a large number of attempts, the present invention unexpectedly found that the use of acetate solvents with a boiling point range of 40-110°C at room temperature and pressure, such as methyl acetate, ethyl acetate, isopropyl acetate, etc., has good solubility for compound 1-F, and is also suitable for the reaction of compound 1-F with compound 1-D-1 or compound 1-D-2, has good universality, can be scaled up, and has application prospects. DETAILED DESCRIPTION

[0029] In order to make the present invention more clearly understood, preferred embodiments are described in detail as follows.

[0030] The percentages not otherwise specified in the present invention refer to mass concentration or mass percentage.

[0031] The purity or content determination in the examples of the present invention is carried out by high performance liquid chromatography.

[0032] In the embodiment of the present invention, the compound 1-F, i.e., 2-[3-chloro-5-(trifluoromethyl)pyridinyl]malonic acid dimethyl ester potassium salt, is prepared according to the method of patent CN116854629A, with a purity of ≥97.0% and a mass content of ≥93.0%; the N-(acetoxymethyl)-2-trifluoromethylbenzamide (i.e., compound 1-D-1) used can be prepared according to patent CN116854629A, with a mass content of ≥97.0%; the N-(chloromethyl)-2-trifluoromethylbenzamide (i.e., compound 1-D-2) used can be prepared according to patent CN116854629A, with a mass content of ≥97.0%. The remaining reagents are all commercially available products with a purity of ≥99.0%.

[0033] Example 1

[0034] In a reaction vessel, add solvent 1 (2232.6 g) and compound 1-F, i.e., 2-[3-chloro-5-(trifluoromethyl)pyridinyl]malonic acid dimethyl ester potassium salt (purity 98%, mass content 94%, 372.1 g, 1.0 mole), control the temperature at 48-53°C, stir for 3-4 hours, until most of compound 1-F is dissolved. Control the dropping temperature at 48-53°C, drop N-(acetoxymethyl)-2-trifluoromethylbenzamide (i.e., compound of formula 1-D-1) (mass content 97%, 274.7 g, 1.02 mole) and solvent 1 (372.1 g) into the reaction vessel, after the dropping is complete, heat to the reaction temperature of 50-55°C, continue stirring the reaction, react for 4 hours, until the conversion is qualified, take a sample at point 1, at which time the purity of the intermediate compound of formula 1-G is 97.9%. The distillation temperature was controlled to be 40-100°C, the vacuum degree was -0.080 to -0.098 MPa, and the solvent 1 was distilled and recovered until almost no solvent 1 was distilled out. The recovered solvent 1 was 2364.4 g, and the recovery rate of solvent 1 was 94.3%. At sampling point 2, the purity of the intermediate compound 1-G was 97.8%, and the residual amount of solvent 1 in the intermediate compound 1-G was 1.5%. 624.8 g of the product intermediate compound 1-G was obtained, and the mass content of the product was detected, and the calculated molar yield was 97.7% (calculated as 2-[3-chloro-5-(trifluoromethyl)pyridinyl]malonic acid dimethyl ester potassium salt).

[0035] In this Example 1, the solvent 1 is ethyl acetate.

[0036] Example 2

[0037] In a 50-liter reaction vessel, add solvent 1 (21564 g) and compound 1-F, i.e., 2-[3-chloro-5-(trifluoromethyl)pyridinyl]malonic acid dimethyl ester potassium salt (purity 98%, mass content 94%, 3535 g, 9.5 mol), control the temperature at 48-54°C, stir for 3-4 hours, until most of compound 1-F is dissolved. Control the dropping temperature at 48-54°C, drop N-(acetoxymethyl)-2-trifluoromethylbenzamide (i.e., compound 1-D-1) (mass content 97%, 2609 g, 9.69 mol) and solvent 1 (3535 g) into the reaction vessel, after the drop is complete, heat to the reaction temperature of 50-55°C, continue stirring the reaction, react for 4 hours, until the conversion is qualified, sample point 1, at which time the purity of the intermediate compound 1-G is 97.6%. The distillation temperature was controlled to be 40-100°C, the vacuum degree was -0.080 to -0.098 MPa, and the solvent 1 was distilled and recovered until almost no solvent 1 was distilled out. The recovered solvent 1 was 23718 g, and the recovery rate of solvent 1 was 94.5%. At sampling point 2, the purity of the intermediate compound 1-G was 97.4%, and the residual amount of solvent 1 in the intermediate compound 1-G was 1.3%. 5944 g of the product intermediate compound 1-G was obtained, and the mass content of the product was detected, and the molar yield was calculated to be 97.2% (calculated as 2-[3-chloro-5-(trifluoromethyl)pyridinyl]malonic acid dimethyl ester potassium salt).

[0038] In this Example 2, the solvent 1 is ethyl acetate.

[0039] Embodiments 3 to 8

[0040] A process for preparing a key intermediate of fluopyram, which differs from Example 1 in that the process parameters of the process are different, for example, the difference between Example 3 and Example 1 is only the difference in the reaction substrate compound 1-D, in Example 3, the compound 1-D is selected from the formula 1-D-2, i.e., N-(chloromethyl)-2-trifluoromethylbenzamide, and in Example 1, the compound 1-D is selected from the formula 1-D-1, i.e., N-(acetoxymethyl)-2-trifluoromethylbenzamide, and the other conditions are the same. The specific differences of other embodiments are shown in Table 1.

[0041] Table 1. Preparation method parameters of Examples 3 to 8

[0042]

[0043]

[0044] The samples at each sampling point and the products obtained in Examples 3 to 8 were subjected to high performance liquid chromatography (HPLC) purity and molar yield calculations. The results are shown in Table 2.

[0045] Table 2. Sample purity and molar yield of each sampling point in Examples 3 to 8

[0046]

[0047] Combining the data of Examples 1 to 8 and Tables 1 and 2, it can be seen that ethyl acetate, methyl acetate, and isopropyl acetate are all suitable for the process of the present invention. The process using these acetate solvents can produce an intermediate compound 1-G with a purity of ≥95.8%, and up to 97.8%.

[0048] Combined with the data of Examples 1 to 8 and Tables 1 and 2, it can be seen that in the process of the present application, the reaction intermediate compound 1-G obtained has high purity and few organic impurities; secondly, these acetate solvents are easy to recover, the conditions are mild, the solvent recovery rate is high, and basically no new impurities are generated during the solvent recovery process. At the same time, the process has the characteristics of high total yield. The molar yield of the intermediate compound 1-G obtained by the process is ≥95.5%, and can reach up to 97.7% (calculated as 2-[3-chloro-5-(trifluoromethyl)pyridinyl]malonic acid dimethyl ester potassium salt).

[0049] Example 9

[0050] In a reaction vessel, add solvent 1 (2232.6 g) and compound 1-F, i.e., potassium salt of dimethyl 2-[3-chloro-5-(trifluoromethyl)pyridinyl]malonate (purity 98%, mass content 94%, 372.1 g, 1.0 mole), control the temperature at 48-53°C, stir for 3-4 hours, until most of compound 1-F is dissolved. Control the dropping temperature at 48-53°C, drop a solution prepared by N-(acetoxymethyl)-2-trifluoromethylbenzamide (i.e., compound of formula 1-D-1) (mass content 97%, 274.7 g, 1.02 mole) and solvent 1 (372.1 g) into the reaction vessel, after the dropping is complete, raise the temperature to the reaction temperature of 50-55°C, continue stirring the reaction, react for 4 hours, until the conversion is qualified, take a sample at point 1, at which time the purity of the intermediate compound 1-G is 97.9%. The distillation temperature was controlled to be 40-100°C, the vacuum degree was -0.080~-0.098Mpa, and the solvent 1 was distilled and recovered until almost no solvent 1 was distilled out. The recovered solvent 1 was 2364.4g, and the recovery rate of solvent 1 was 94.3%. The sampling point 2, at this time, the purity of the intermediate compound 1-G was 97.8%, and the residual amount of solvent 1 in the intermediate compound 1-G was 1.5%. Methanol (632.6g) was added to the reaction container, refluxed and stirred for about 0.5-1.0 hours, and after the material was basically dissolved, the temperature was lowered to 35-40°C, and the prepared sodium hydroxide aqueous solution (including 121g of sodium hydroxide, 3.0 moles; 930.3g of water) was added, the temperature was maintained at 35-40°C, PH=14, and the reaction was carried out for 3-6 hours until the conversion was qualified, and the purity of the intermediate compound 1-G was ≤0.5%. Hydrochloric acid is added dropwise to the reaction vessel, pH is adjusted to 2-3, the temperature is controlled at 55-60°C, and the reaction is continued for 2-4 hours until the conversion is qualified, at which time the purity of the product fluopyram is 94.9%. After the reaction is completed, a small amount of sodium hydroxide aqueous solution is added to the reaction vessel, pH is adjusted to 6.5-7.5, the temperature is lowered to 15-25°C, filtered, the solid is washed with water pulping, filtered, and dried to obtain the product fluopyram, with a molar yield of 92.5% (calculated as 2-[3-chloro-5-(trifluoromethyl)pyridyl]malonic acid dimethyl ester potassium salt). After testing, the product fluopyram purity is 99.0%, the mass content is 98.8%, the water content is 0.4%, the pH is 6.5, and the acetone insoluble matter is 0.4%.

[0051] In this Example 9, the solvent 1 is ethyl acetate.

[0052] Comparative Examples 1 to 6

[0053] A process for preparing a key intermediate of fluopyram, wherein comparative examples 1 to 6 differ from example 3 only in the process parameters of the process, and other conditions are the same. The specific differences are shown in Table 3.

[0054] Table 3. Preparation method parameter table of comparative examples 1 to 6

[0055]

[0056] The samples at each sampling point and the products obtained in Comparative Examples 1 to 6 were subjected to high performance liquid chromatography (HPLC) purity and molar yield calculations. The results are shown in Table 4.

[0057] Table 4. Sample purity and molar yield of each sampling point in comparative examples 1 to 6

[0058]

[0059] In combination with Examples 1 to 8, the data of Comparative Examples 1 to 6 and Tables 1, 2, 3 and 4 show that solvents such as N,N-dimethylacetamide, N-methylpyrrolidone, 1,2-dichloroethane, formamide and acetic acid have relatively poor effects in the process method. For example, when N,N-dimethylacetamide, N-methylpyrrolidone and formamide are used as solvents, the condensation reaction effect is acceptable at the beginning, but during distillation, the purity of the intermediate compound of Formula 1-G is significantly low. By using the process method of the present invention, the reaction effects of different solvents are compared. When the preferred acetate solvent of the present invention is selected, the reaction effect is significantly better than that of N,N-dimethylacetamide, N-methylpyrrolidone, 1,2-dichloroethane, formamide and acetic acid. By using the process method of the present invention, the reaction effect of the preferred acetate solvent of the present invention is also better than that of other ester solvents such as n-butyl acetate.

[0060] The above description is only a preferred embodiment of the present invention and is not any formal or substantial limitation of the present invention. It should be pointed out that a person skilled in the art can make several improvements and supplements without departing from the present invention, and these improvements and supplements should also be regarded as the protection scope of the present invention.

Claims

1. A process for preparing a key intermediate of fluopyram, characterized in that: The method comprises the following steps: in the presence of solvent 1, compound 1-F, i.e., 2-[3-chloro-5-(trifluoromethyl)pyridinyl]malonate dimethyl potassium salt, and compound 1-D are reacted in a reaction container, and after the reaction, solvent 1 is recovered by distillation to obtain an intermediate compound 1-G; the reaction equation is as follows: Wherein, the compound 1-D is selected from N-(acetoxymethyl)-2-trifluoromethylbenzamide and / or N-(chloromethyl)-2-trifluoromethylbenzamide; the solvent 1 is selected from acetate solvents having a boiling point range of 40-110° C. at normal temperature and pressure.

2. The process according to claim 1, characterized in that: The solvent 1 is selected from one or more combinations of methyl acetate, ethyl acetate and isopropyl acetate.

3. The process according to claim 1, characterized in that: The molar ratio of the compound 1-F to the compound 1-D is 1:0.95-1.10; the mass ratio of the compound 1-F to the solvent 1 is 1:5.0-11.

0.

4. The process according to claim 1, characterized in that: In the steps, the feeding temperature is 40-55°C; the reaction temperature is 40-65°C, and the reaction time is 3-6 hours.

5. The process according to claim 1, characterized in that: The distillation temperature in the distillation recovery solvent 1 is 40-100° C., and the vacuum degree of the distillation is -0.070 to -0.098 MPa.

6. The process according to claim 1, characterized in that: The compound 1-F, ie, 2-[3-chloro-5-(trifluoromethyl)pyridinyl]malonate dimethyl ester potassium salt, has a purity of ≥97.0% and a mass content of ≥93.0%.

7. The process according to claim 1, characterized in that: In the steps, after the solvent 1 is distilled and recovered, the residual amount of the solvent 1 is ≤3%, and the purity of the intermediate compound 1-G is ≥95.8%.

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