Integrated synthesis method of chlorocarbonyl [4-(trifluoromethoxy) phenyl] methyl carbamate

Abstract

The invention belongs to the field of organic synthesis, and particularly provides an integrated synthesis method of chlorocarbonyl [4-(trifluoromethoxy) phenyl] methyl carbamate, which comprises the following steps: dropwise adding methyl chloroformate, slowly dropwise adding a NaOH solution, separating liquid, adding the NaOH solution again, azeotropic with water, and realizing integrated synthesis, thereby obtaining the chlorocarbonyl [4-(trifluoromethoxy) phenyl] methyl carbamate. The intermediate [4-(trifluoromethoxy) phenyl] methyl carbamate can be directly used for preparing sodium salt in the next step without discharging, drying and other operations in the synthesis process, and moisture absorption sensitive substances such as sodium hydride, potassium tert-butoxide, sodium methoxide and the like do not need to be used, so that the safety and stability of the synthesis process are improved.

Description

Technical Field

[0001] The invention belongs to the technical field of pesticides, and specifically relates to an integrated synthesis method of methyl chlorocarbonyl [4-(trifluoromethoxy)phenyl]carbamate. Background Art

[0002] Indoxacarb is an oxadiazine insecticide developed by DuPont in the United States in 1992. This variety has a wide insecticide spectrum and quick effect. It has excellent control effects on resistant pests such as beet armyworm, diamondback moth, and cotton bollworm. Methyl chlorocarbonyl [4- (trifluoromethoxy) phenyl] carbamate is an intermediate of indoxacarb. The existing production process generally generates 4-trifluoromethoxyphenyl carbamate methyl ester intermediate by reacting 4-trifluoromethoxyaniline with methyl chloroformate, and the intermediate is then added with sodium hydride, potassium tert-butoxide, sodium methoxide, etc. to react and synthesize methyl chlorocarbonyl [4- (trifluoromethoxy) phenyl] carbamate. The reagents such as sodium hydride, potassium tert-butoxide, and sodium methoxide used therein are very easy to absorb moisture, and the moisture in the reaction process is difficult to control, and there is a safety hazard that moisture absorption and heat release are easy to catch fire.

[0003] WO2023286053A1 reports the synthesis of methyl chlorocarbonyl [4-trifluoromethoxy)phenyl]carbamate in a two-phase system of water and chlorobenzene using a microchannel reactor. The intermediate 4-trifluoromethoxyphenylcarbamate in this method needs to be separated separately after preparation before entering the next reaction process, which is cumbersome.

[0004] Therefore, there is an urgent need in the prior art for an integrated synthesis process for methyl chlorocarbonyl [4-(trifluoromethoxy)phenyl]carbamate without the need for discharging or other treatment of the intermediate. Summary of the invention

[0005] In order to solve the problems in the prior art that flammable and hygroscopic substances such as sodium hydride, potassium tert-butoxide and sodium methoxide need to be used as raw materials, and 4-trifluoromethoxyphenyl methyl carbamate needs to be separated, the invention provides an integrated synthesis method of chlorocarbonyl [4-(trifluoromethoxy)phenyl] methyl carbamate, wherein a NaOH solution is slowly added after methyl chloroformate is added, and after separation, the NaOH solution is added again to azeotropically carry water to achieve integrated synthesis, wherein the intermediate [4-(trifluoromethoxy)phenyl] methyl carbamate does not need to be discharged, dried or other operations in the synthesis process, and can be directly used for the preparation of sodium salt in the next step, and does not need to use hygroscopic sensitive substances such as sodium hydride, potassium tert-butoxide and sodium methoxide, thereby improving the safety and stability of the synthesis process.

[0006] The integrated synthesis method of chlorocarbonyl [4-(trifluoromethoxy)phenyl] carbamate provided by the present invention has the following reaction equation:

[0007]

[0008] The following steps are involved:

[0009] 1) dissolving triphosgene in a solvent at a ratio of triphosgene mass: solvent volume = 1 g: 2-6 mL, controlling the temperature to -10-50° C., adding a triphosgene depolymerization catalyst, and keeping the depolymerized triphosgene solution at -10-50° C. for later use;

[0010] 2) adding 4-trifluoromethoxyaniline to a solvent at -10 to 50°C, maintaining the system temperature at -10 to 50°C, slowly dropping methyl chloroformate, and after the dropwise addition is completed, keeping the temperature for 2 to 3 hours, slowly adding a NaOH solution, maintaining the system temperature at -10 to 50°C, and continuing to stir for 5 to 7 hours. After the reaction is completed, the liquids are separated, and the organic phase is washed with water until the pH of the washing water is 6 to 7 to obtain methyl [4-(trifluoromethoxy)phenyl]carbamate;

[0011] 3) adding NaOH solution again to the methyl [4-(trifluoromethoxy)phenyl]carbamate obtained in step 2) to azeotropically carry out water to generate the sodium salt of methyl [4-(trifluoromethoxy)phenyl]carbamate;

[0012] 4) adding the sodium salt system obtained in step 3) to the depolymerized triphosgene solution in step 1) to react for 0.5 to 1 h, pouring the reaction solution into ice water, stirring and separating the liquids, washing with water, and desolventizing to obtain methyl chlorocarbonyl [4-(trifluoromethoxy)phenyl]carbamate.

[0013] Preferably, the triphosgene depolymerization catalyst in step 1) is one of pyridine, triethylamine, diisopropylethylamine, N,N-dimethylaniline and 4-dimethylaminopyridine.

[0014] Preferably, in step 1), the mass of the triphosgene depolymerization catalyst is 0.1 to 0.3% of the mass of the triphosgene.

[0015] Preferably, the same solvent is used in steps 1) and 2), and the solvent is toluene or 1,2-dichloroethane.

[0016] Preferably, the molar ratio of 4-trifluoromethoxyaniline to methyl chloroformate in step 2) is 1:(1-1.5), more preferably 1:(1.2-1.5).

[0017] Preferably, the volume of the solvent in step 2) is 3 to 10 times the volume of the solvent used to prepare the triphosgene solution in step 1).

[0018] As a preferred embodiment, the molar ratio of methyl chloroformate to NaOH in step 2) is 1:1; the molar ratio of NaOH to 4-trifluoromethoxyaniline in step 2) is 1:1. In step 2), sodium hydroxide is used to consume the hydrogen chloride generated after the reaction of methyl chloroformate, and the molar ratio of 1:1 is just enough to react with the generated hydrogen chloride. Too much sodium hydroxide in step 3) will consume solid phosgene, and too little sodium hydroxide will not completely react.

[0019] Preferably, in step 2), the reaction temperature for synthesizing methyl [4-(trifluoromethoxy)phenyl]carbamate is -10 to 30°C, more preferably -10 to 10°C, and most preferably -10 to 0°C.

[0020] Preferably, the temperature of azeotropic water distillation in step 3) is 60-70° C., and the azeotropic water distillation is performed until no water is evaporated.

[0021] Preferably, the amount of triphosgene solution used for depolymerization in step 4) is such that the molar ratio of 4-trifluoromethoxyaniline in step 2) to triphosgene in step 1) is 1:(0.33-0.7).

[0022] Preferably, the optimal reaction temperature of the sodium salt system and the depolymerized triphosgene solution in step 4) is -10 to 0°C.

[0023] The method of the present invention is used to synthesize chlorocarbonyl [4-(trifluoromethoxy)phenyl] carbamate methyl, and the following technical effects are achieved:

[0024] 1) The synthesis method does not require the use of sensitive and hygroscopic reagents such as sodium hydride, potassium tert-butoxide, and sodium methoxide, thereby avoiding the problem of difficult control of moisture during the reaction, the existence of hygroscopic heat release and easy ignition, and also does not use sodium carbonate with carbon dioxide gas as a byproduct, thereby avoiding the risk of volume expansion and easy material impact due to gas release during the reaction, thereby improving the controllability and safety of the synthesis process;

[0025] 2) After the intermediate [4-(trifluoromethoxy)phenyl]carbamic acid methyl ester is prepared by the synthesis method, no discharging, drying and other operations are required, and the next step of azeotropic water-carrying operation can be directly carried out, thereby realizing integrated synthesis, simple reaction, and convenient for scale-up production;

[0026] 3) The synthetic method of the present invention is used to prepare methyl chlorocarbonyl [4-(trifluoromethoxy)phenyl]carbamate, and the reaction conversion rate can reach more than 99%, and the raw materials are basically completely converted;

[0027] 4) The product is easy to separate and the operation is simple. Toluene and 1,2-dichloroethane are used as solvents. The generated inorganic salt directly enters the aqueous phase after washing and separation, and the product remains in the organic phase, without the need for cumbersome post-treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 This is the HNMR detection spectrum of the product in Example 1. DETAILED DESCRIPTION

[0029] In order to enable those skilled in the art to better understand the technical solutions in the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work should fall within the scope of protection of the present invention.

[0030] Example 1

[0031] A method for synthesizing methyl chlorocarbonyl [4-(trifluoromethoxy)phenyl]carbamate in an integrated manner comprises the following steps:

[0032] To a 500ml four-necked bottle, add 50ml of toluene and 20.8g (0.07mol) of triphosgene in sequence under stirring. After the addition is completed, cool to -5 to 0°C. After the triphosgene is completely dissolved, add 0.03g of pyridine. Keep stirring and keep warm for later use.

[0033] At -5-0°C, add 150 ml of toluene and 17.7 g (0.1 mol) of 4-trifluoromethoxyaniline in a 500 ml four-necked reaction flask with stirring. Keep the temperature at -5-0°C, slowly add 11.3 g (0.12 mol) of methyl chloroformate dropwise, and keep warm for 2 h. Keep the temperature at -5-0°C and add 16 g (0.12 mol) of 30% sodium hydroxide solution dropwise, and continue to react at this temperature for 5 h after the addition of sodium hydroxide is completed. Check that the raw material is completely converted by HPLC. Let it stand for 0.5 h, separate the liquid to remove the aqueous phase, and wash the organic phase with water three times (150 ml×3) until the pH of the washing water is 6-7.

[0034] Under stirring, 13.3 g (0.1 mol) of 30% sodium hydroxide was added to the organic phase again, and the temperature was raised to 65-70°C. The reduced pressure azeotropic distillation with water was carried out for about 8 hours. No water was evaporated in the water separator. The reduced pressure azeotropic distillation with water was continued for 2 hours. At this time, samples were taken for HPLC detection, and the raw material conversion was complete.

[0035] The temperature was lowered to -5 to 0°C, and the system was slowly added dropwise to the depolymerized triphosgene. The reaction temperature was kept at -5 to 0°C throughout the process. After the addition was completed, the temperature was kept for 0.5h. Samples were taken for GC detection. The raw material conversion was complete. The reaction solution was poured into 200g of ice water, stirred and separated, and the organic phase was washed with ice water three times (200g×3). The product was desolvated under negative pressure to obtain 29.9g of the product, with a yield of 99.1%. The product was tested by HPLC, and the purity was 98.6%.

[0036] The product was tested by HNMR, and its HNMR spectrum was as follows: Figure 1 As shown, the test data is as follows:

[0037] 1H NMR (500MHz, CDCl3): δ7.32 (s, 4H), 3.84 (s, 3H).

[0038] Example 2

[0039] A method for integrated synthesis of methyl chlorocarbonyl [4-(trifluoromethoxy)phenyl]carbamate, the steps are consistent with those described in Example 1, except that the temperature of the first two steps is controlled at 0-10° C., and the amount of triphosgene used is 17.8 g (0.06 mol). Specifically, 50 ml of toluene and 17.8 g (0.06 mol) of triphosgene are sequentially added to a 500 ml four-necked bottle under stirring, the temperature is lowered to 0-10° C., 0.03 g of pyridine is added after the triphosgene is completely dissolved, the stirring state is maintained, and the mixture is kept warm for standby use.

[0040] The product was desolventized under negative pressure to obtain 29.8 g of product with a yield of 99.0%. The product was tested by HPLC and the purity was 98.9%.

[0041] Example 3

[0042] A method for integrated synthesis of methyl chlorocarbonyl [4-(trifluoromethoxy)phenyl]carbamate, the steps are consistent with those described in Example 1, except that the amount of triphosgene used is 14.8 g (0.05 mol), specifically, 50 ml of toluene and 14.8 g (0.05 mol) of triphosgene are sequentially added into a 500 ml four-necked bottle under stirring, the temperature is lowered to -5 to 0°C, 0.03 g of pyridine is added after the triphosgene is completely dissolved, the stirring state is maintained, and the mixture is kept warm for standby use.

[0043] The product was desolventized under negative pressure to obtain 29.8 g of product with a yield of 99.1%. The product was tested by HPLC and the purity was 99.0%.

[0044] Example 4

[0045] A method for integrated synthesis of methyl chlorocarbonyl [4-(trifluoromethoxy)phenyl] carbamate, the steps are consistent with those described in Example 1, except that the amount of triphosgene used is 11.9 g (0.04 mol), specifically, 50 ml of toluene and 11.9 g (0.04 mol) of triphosgene are sequentially added into a 500 ml four-necked bottle under stirring, the temperature is lowered to -5 to 0°C, 0.03 g of pyridine is added after the triphosgene is completely dissolved, the stirring state is maintained, and the mixture is kept warm for standby use.

[0046] The product was desolventized under negative pressure to obtain 29.7 g of product with a yield of 99.3%. The product was tested by HPLC and the purity was 99.5%.

[0047] Example 5

[0048] A method for synthesizing methyl chlorocarbonyl [4-(trifluoromethoxy)phenyl]carbamate in an integrated manner comprises the following steps:

[0049] To a 500ml four-necked bottle, add 50ml of toluene and 11.9g (0.04mol) of triphosgene in sequence under stirring, cool to -10 to -5°C, add 0.03g of pyridine after all the triphosgene is dissolved, keep stirring, and keep warm for later use.

[0050] At -10~-5℃, add 150ml of toluene and 17.7g (0.1mol) of 4-trifluoromethoxyaniline in turn to a 500ml four-necked reaction flask with stirring, maintain -10~-5℃, slowly add 14.2g (0.15mol) of methyl chloroformate dropwise, keep warm for 2h after the addition is completed, add 20.0g (0.15mol) of 30% sodium hydroxide solution dropwise while maintaining the temperature at -10~-5℃, continue to react at this temperature for 5h after the addition of sodium hydroxide is completed, check that the raw material is completely converted by HPLC, let stand for 0.5h, separate the liquid to remove the aqueous phase, wash the organic phase with water three times (150ml×3) until the pH of the washing water is 6~7.

[0051] Under stirring, 13.3 g (0.1 mol) of 30% sodium hydroxide was added to the organic phase again, and the temperature was raised to 65-70°C. The reduced pressure azeotropic distillation with water was carried out for about 8 hours. No water was evaporated in the water separator. The reduced pressure azeotropic distillation with water was continued for 2 hours. At this time, samples were taken for HPLC detection, and the raw material conversion was complete.

[0052] The temperature was lowered to -10 to -5°C, and the system was slowly added dropwise to the depolymerized triphosgene. The reaction temperature was kept at -10 to -5°C throughout the process. After the addition was completed, the temperature was kept for 0.5h. The raw material was sampled for GC detection. The conversion of the raw material was complete. The reaction solution was poured into 200g of ice water, stirred and separated, and the organic phase was washed with ice water three times (200g×3). The product was desolvated under negative pressure to obtain 29.9g of the product, with a yield of 99.5%. The product was tested by HPLC, and the purity was 99.0%.

[0053] Example 6

[0054] A method for synthesizing methyl chlorocarbonyl [4-(trifluoromethoxy)phenyl]carbamate in an integrated manner comprises the following steps:

[0055] To a 500ml four-necked bottle, add 50ml of toluene and 11.9g (0.04mol) of triphosgene in sequence under stirring, cool to -5-0°C, add 0.03g of pyridine after all the triphosgene is dissolved, keep stirring, and keep warm for later use.

[0056] At -5-0°C, add 150 ml of toluene and 17.7 g (0.1 mol) of 4-trifluoromethoxyaniline in a 500 ml four-necked reaction flask with stirring, cool to -5-0°C, slowly drop 11.3 g (0.12 mol) of methyl chloroformate, keep warm for 2 h after the addition is completed, add 16 g (0.12 mol) of 30% sodium hydroxide solution dropwise while maintaining the temperature at -5-0°C, continue to react at this temperature for 5 h after the addition of sodium hydroxide is completed, check that the raw material is completely converted by HPLC, let stand for 0.5 h, separate the liquid to remove the aqueous phase, wash the organic phase with water three times (150 ml×3) until the pH of the washing water is 6-7.

[0057] Under stirring, 13.3 g (0.1 mol) of 30% sodium hydroxide was added to the organic phase again, and the temperature was raised to 60-65°C. The reduced pressure azeotropic distillation was carried out for about 12 hours. No water was evaporated in the water separator. The reduced pressure azeotropic distillation was continued for 2 hours. At this time, samples were taken for HPLC detection, and the raw material conversion was complete.

[0058] The temperature was lowered to -5 to 0°C, and the system was slowly added dropwise to the depolymerized triphosgene. The reaction temperature was kept at -5 to 0°C throughout the process. After the addition was completed, the temperature was kept for 0.5h. Samples were taken for GC detection. The raw material conversion was complete. The reaction solution was poured into 200g of ice water, stirred and separated, and the organic phase was washed with ice water three times (200g×3). The product was desolvated under negative pressure to obtain 29.7g of the product, with a yield of 99.4%. The product was tested by HPLC, and the purity was 99.6%.

[0059] Example 7

[0060] A method for synthesizing methyl chlorocarbonyl [4-(trifluoromethoxy)phenyl]carbamate in an integrated manner comprises the following steps:

[0061] Under stirring, add 50 ml of 1,2-dichloroethane, 50 ml of triphosgene,

[0062] 11.9g (0.04mol), cool to -5~0℃, add 0.03g pyridine after all triphosgene is dissolved, keep stirring, and keep warm for later use.

[0063] Under stirring, add 150 ml of 1,2-dichloroethane and 17.7 g (0.1 mol) of 4-trifluoromethoxyaniline to a 500 ml four-necked reaction flask in sequence, cool to -5-0°C, slowly drop 11.3 g (0.12 mol) of methyl chloroformate, keep warm for 2 h after the addition is completed, add 16 g (0.12 mol) of 30% sodium hydroxide solution dropwise at -5-0°C, continue to react at this temperature for 5 h after the addition of sodium hydroxide is completed, check that the raw material is completely converted by HPLC, let stand for 0.5 h, separate the liquid to remove the aqueous phase, and wash the organic phase with water three times (150 ml × 3) until the pH of the washing water is 6-7.

[0064] Under stirring, 13.3 g (0.1 mol) of 30% sodium hydroxide was added to the organic phase again, and the temperature was raised to 65-70°C. The reduced pressure azeotropic distillation was carried out for about 11 hours. No water was evaporated in the water separator. The reduced pressure azeotropic distillation was maintained for 2 hours. At this time, sampling was carried out for HPLC detection, and the raw material conversion was complete.

[0065] The temperature was lowered to -5 to 0°C, and the system was slowly added dropwise to the depolymerized triphosgene. The reaction temperature was kept at -5 to 0°C throughout the process. After the addition was completed, the temperature was kept for 0.5h. Samples were taken for GC detection. The raw material conversion was complete. The reaction solution was poured into 200g of ice water, stirred and separated, and the organic phase was washed with ice water three times (200g×3). The product was desolvated under negative pressure to obtain 29.1g of the product, with a yield of 97.1%. The product was tested by HPLC, and the purity was 99.3%.

[0066] Comparative Example 1

[0067] A method for integrated synthesis of methyl chlorocarbonyl [4-(trifluoromethoxy)phenyl]carbamate, the steps are consistent with those described in Example 1, except that the amount of triphosgene used is 9.9 g (0.033 mol), specifically, 50 ml of toluene and 9.9 g (0.033 mol) of triphosgene are sequentially added into a 500 ml four-necked bottle under stirring, the temperature is lowered to -5 to 0°C, 0.03 g of pyridine is added after the triphosgene is completely dissolved, the stirring state is maintained, and the mixture is kept warm for standby use.

[0068] The product was desolventized under negative pressure to obtain 28.2 g, with a yield of 87.1%. The product was tested by HPLC, and the purity was 91.9%. This comparative example shows that the reaction is not complete when the amount of triphosgene is low.

[0069] Comparative Example 2

[0070] The invention discloses an integrated method for synthesizing methyl chlorocarbonyl [4-(trifluoromethoxy)phenyl]carbamate. The method comprises the following steps: adding 150 ml of toluene and 17.7 g (0.1 mol) of 4-trifluoromethoxyaniline into a 500 ml four-necked reaction bottle in sequence under stirring, cooling the bottle to -5 to 0 DEG C, slowly dropping 10.4 g (0.11 mol) of methyl chloroformate, keeping the temperature for 2 hours after the dropping, dropping 14.7 g (0.11 mol) of a sodium hydroxide solution with a mass concentration of 30% at a temperature maintained at -5 to 0 DEG C, continuing the reaction at the temperature for 5 hours after the dropping of the sodium hydroxide, and checking by HPLC that the remaining raw material is 3.1%.

[0071] This comparative example shows that methyl chloroformate is partially decomposed in the system. When the methyl chloroformate equivalent is small, the reaction cannot be completed and there is obvious residual raw material.

[0072] Comparative Example 3

[0073] A method for synthesizing methyl chlorocarbonyl [4-(trifluoromethoxy)phenyl]carbamate in an integrated manner comprises the following steps:

[0074] At -5-0°C, add 150 ml of toluene and 17.7 g (0.1 mol) of 4-trifluoromethoxyaniline in a 500 ml four-necked reaction flask with stirring, cool to -5-0°C, slowly add 11.3 g (0.12 mol) of methyl chloroformate dropwise, keep warm for 2 h after the addition is completed, add 16 g (0.12 mol) of 30% sodium hydroxide solution dropwise while maintaining the temperature at -5-0°C, continue to react at this temperature for 5 h after the addition of sodium hydroxide is completed, check that the raw material is completely converted by HPLC, let stand for 0.5 h, separate the liquid to remove the aqueous phase, wash the organic phase with water three times (150 ml×3) until the pH of the washing water is 6-7. Under stirring, 13.3 g (0.1 mol) of 30% sodium hydroxide was added to the organic phase again, and the temperature was raised to 70-75°C. The reduced pressure azeotropic distillation with water was continued until no water was evaporated in the water separator. The reduced pressure azeotropic distillation with water was continued for 2 hours. At this time, a sample was taken for HPLC detection, and the intermediate sodium salt was decomposed.

[0075] The temperature of the azeotropic water is another key technical feature in the present application. In this comparative example, since the temperature of the reduced pressure azeotropic water exceeds 70°C, the raw materials decompose and cannot form a stable intermediate.

[0076] According to the experimental data of Examples 1-4, it can be seen that when the feed ratio of 4-trifluoromethoxyaniline to triphosgene is 1:0.4-0.7, the raw material can be completely converted. According to the experimental data of Comparative Example 1, it can be seen that when the feed ratio of 4-trifluoromethoxyaniline to triphosgene is 1:0.33, there is a surplus of raw materials and the yield of the product is low. According to the experimental data of Comparative Example 2, it can be seen that when the feed ratio of 4-trifluoromethoxyaniline to methyl chloroformate is 1:1.1, there is a surplus of raw material 4-trifluoromethoxyaniline. According to the experimental data of Comparative Example 3, when the water temperature is 70-75°C, the sodium salt intermediate decomposes and the target product cannot be obtained.

[0077] It can be seen from the above results that the integrated synthesis technology of methyl chlorocarbonyl [4-trifluoromethoxy) phenyl] carbamate provided by the present invention can achieve a product purity of more than 99%, a product yield of more than 99%, and an integrated synthesis is achieved without discharging in the intermediate process, and there is no need to use moisture-sensitive substances such as sodium hydride, potassium tert-butoxide, and sodium methoxide, thereby improving the safety and stability of the synthesis process.

[0078] Although the present invention has been described in detail by referring to the accompanying drawings and in combination with the preferred embodiments, the present invention is not limited thereto. Without departing from the spirit and essence of the present invention, a person of ordinary skill in the art may make various equivalent modifications or substitutions to the embodiments of the present invention, and these modifications or substitutions shall be within the scope of the present invention. Any person of ordinary skill in the art may easily think of changes or substitutions within the technical scope disclosed by the present invention, and these shall be within the scope of protection of the present invention. Therefore, the scope of protection of the present invention shall be subject to the scope of protection described in the claims.

Claims

1. An integrated synthesis method of methyl chlorocarbonyl [4-(trifluoromethoxy)phenyl]carbamate, characterized in that: The following steps are involved: 1) dissolving triphosgene in a solvent at a ratio of triphosgene mass: solvent volume = 1 g: 2-6 mL, controlling the temperature to -10-50° C., adding a triphosgene depolymerization catalyst, and keeping the depolymerized triphosgene solution at -10-50° C. for later use; 2) adding 4-trifluoromethoxyaniline to a solvent at -10 to 50°C, maintaining the system temperature at -10 to 50°C, slowly dropping methyl chloroformate, and after the dropwise addition is completed, keeping the temperature for 2 to 3 hours, slowly adding a NaOH solution, maintaining the system temperature at -10 to 50°C, and continuing to stir for 5 to 7 hours. After the reaction is completed, the liquids are separated, and the organic phase is washed with water until the pH of the washing water is 6 to 7 to obtain methyl [4-(trifluoromethoxy)phenyl]carbamate; 3) adding NaOH solution again to the methyl [4-(trifluoromethoxy)phenyl]carbamate obtained in step 2) to azeotropically carry out water to generate the sodium salt of methyl [4-(trifluoromethoxy)phenyl]carbamate; 4) adding the sodium salt system obtained in step 3) to the depolymerized triphosgene solution in step 1) to react for 0.5 to 1 h, pouring the reaction solution into ice water, stirring and separating the liquids, washing with water, and desolventizing to obtain methyl chlorocarbonyl [4-(trifluoromethoxy)phenyl]carbamate.

2. The integrated synthesis method of methyl chlorocarbonyl [4-(trifluoromethoxy)phenyl]carbamate according to claim 1, characterized in that: The triphosgene depolymerization catalyst in step 1) is one of pyridine, triethylamine, diisopropylethylamine, N,N-dimethylaniline and 4-dimethylaminopyridine.

3. The integrated synthesis method of methyl chlorocarbonyl [4-(trifluoromethoxy)phenyl]carbamate according to claim 1 or 2, characterized in that: The mass of the triphosgene depolymerization catalyst in step 1) is 0.1-0.3% of the mass of the triphosgene.

4. The integrated synthesis method of methyl chlorocarbonyl [4-(trifluoromethoxy)phenyl]carbamate according to claim 1, characterized in that: The same solvent is used in steps 1) and 2), and the solvent is toluene or 1,2-dichloroethane.

5. The integrated synthesis method of methyl chlorocarbonyl [4-(trifluoromethoxy)phenyl]carbamate according to claim 1, characterized in that: In step 2), the molar ratio of 4-trifluoromethoxyaniline to methyl chloroformate is 1:(1-1.5), and the reaction temperature is -10-30°C.

6. The integrated synthesis method of methyl chlorocarbonyl [4-(trifluoromethoxy)phenyl]carbamate according to claim 1, characterized in that: The volume of the solvent in step 2) is 3 to 10 times the volume of the solvent used to prepare the triphosgene solution in step 1).

7. The integrated synthesis method of methyl chlorocarbonyl [4-(trifluoromethoxy)phenyl]carbamate according to claim 1, characterized in that: The molar ratio of methyl chloroformate to NaOH in step 2) is 1:1; the molar ratio of NaOH in step 3) to 4-trifluoromethoxyaniline in step 2) is 1:

1.

8. The integrated synthesis method of methyl chlorocarbonyl [4-(trifluoromethoxy)phenyl]carbamate according to claim 1 or 5, characterized in that: The reaction temperature in step 2) is -10 to 0°C.

9. The integrated synthesis method of methyl chlorocarbonyl [4-(trifluoromethoxy)phenyl]carbamate according to claim 1, characterized in that: Step 3) The temperature of the azeotropic water is 60-70° C., and the azeotropic water is evaporated until no water is evaporated.

10. The integrated synthesis method of methyl chlorocarbonyl [4-(trifluoromethoxy)phenyl]carbamate according to claim 1, characterized in that: The amount of the depolymerized triphosgene solution used in step 4) is based on a molar ratio of 4-trifluoromethoxyaniline in step 2) to triphosgene in step 1) of 1:(0.33-0.7); in step 4), the reaction temperature of the sodium salt system and the depolymerized triphosgene solution is -10-0°C.

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