CN110577484A - Method and device for continuous synthesis of cyclopropane compounds - Google Patents

Abstract

The invention discloses a method and a device for continuously synthesizing cyclopropane compounds. The method comprises the steps of: continuously performing the synthesis reaction of the diazomethane precursor in the first reactor, the reaction product of the first reactor flows into the separator for stratification, and the organic phase obtained by stratification overflows into the second reaction In the second reactor, the diazomethane precursor is continuously consumed to prepare diazomethane, and the electron-rich monoolefin cyclopropanation reaction is carried out in situ to obtain cyclopropane compounds. Applying the technical scheme of the present invention can realize automatic control, reduce the transfer of high-risk materials, avoid the risk of pipeline transfer of diazomethane solution, and effectively improve production safety; moreover, the equipment is simple, can save equipment investment, and can safely and quantitatively Simultaneously realize the formation of diazomethane and the cyclopropanation reaction of olefins.

Description

Method and device for continuous synthesis of cyclopropane compounds

technical field

The invention relates to the field of medicine and chemical industry, in particular to a method and device for continuous synthesis of cyclopropane compounds.

Background technique

Cyclopropane compounds can participate in the construction of various heterocyclic compound skeletons due to the tension of the three-membered ring and the unique double bond characteristics. Many natural products and active ingredients are cyclopropane compounds or derived from cyclopropane compounds. It has important application value in the field of medicine and chemical industry. Synthesis of cyclopropane compounds by cyclopropanation of alkenes is a common way.

The Simmons-Smith reaction is a widely used reaction in the cyclopropanation reaction of olefins. Diethyl zinc or zinc-copper alkene, diiodomethane (or methylene bromide) produces carbene intermediates and reacts with olefins to generate cyclopropanes compound. This type of reaction is easy to scale up and produce good yields. However, since the amount of metal-organic reagents is stoichiometric, a large amount of metal waste will be generated after the reaction is completed, which increases environmental pollution and waste disposal costs.

Using catalytic amount of transition metal to catalyze the cycloaddition of diazonium compound to alkenes is a very effective way to synthesize cyclopropane compound. In the presence of transition metal complexes, diazo compounds are easily decomposed to form metal carbene intermediates and release nitrogen, and metal carbene reacts with olefinic bonds to generate cyclopropane products. This type of reaction theoretically only produces by-product nitrogen, which has a high The atomic economy greatly reduces the cost of post-processing. Diazomethane is a commonly used diazo compound for the synthesis of unsubstituted three-membered rings. However, diazomethane is volatile, highly toxic, and carcinogenic. Compounds including diazomethane precursors are sensitive to light, high temperature, impact, and friction, and may cause decomposition and explosion. These factors limit the large-scale application of diazomethane in traditional batch reactions.

In recent years, Hansjoerg Lehmann et al. have carried out continuous preparation of diazomethane precursor (MNU) and continuous preparation and application of diazomethane solution, which can greatly reduce the risk of separation and use of diazomethane precursor and diazomethane. However, the continuous reaction equipment chain is long and involves the risk of pipeline transfer of diazomethane solution. Doris Dallinger etc. continuously prepared diazomethane and at the same time separated pure diazomethane and reacted with the substrate through permeable membrane technology. Although they successfully realized the simultaneous preparation and application of diazomethane and shortened the equipment chain, the permeable membrane The manufacturing cost is high, the production capacity is small, and large-scale application cannot be realized in a short time. Oleg M. Nefedov et al. realized the in-situ cyclopropanation of electron-rich monoolefins (without obvious conjugated structure) by in-situ generation of diazomethane, which can be efficiently carried out using traditional palladium catalysts. Bill Morandi et al. used an improved iron-based catalyst and a one-pot method to realize in situ generation of diazomethane and highly selective cyclopropanation of conjugated olefins. Both of these studies rely on the controlled feeding of the diazomethane precursor to realize the simultaneous formation of diazomethane and the cyclopropanation of olefins in a two-phase system. If the feeding rate of the diazomethane precursor is too fast, the diazomethane unit The amount of production is large within a period of time, and the catalyst catalyzes the decomposition of diazomethane at an accelerated rate to generate by-products such as ethylene. If the feeding rate is too slow, it may cause the precipitation of the catalyst and affect the catalytic activity. These all increase the risk of operating the diazomethane precursor.

In summary, the prior art mainly has the following disadvantages: 1) Although the continuous preparation of the diazomethane precursor and the continuous preparation and application of the diazomethane solution can be realized, the separation of the diazomethane precursor and the diazomethane can be greatly reduced And the risk of use, but the continuous reaction equipment chain is long and involves the pipeline transfer risk of diazomethane solution; 2) prepare diazomethane by continuous reaction, though permeable membrane separation of diazomethane can realize the separation of diazomethane and substrate In-situ reaction, but the manufacturing cost of the permeable membrane is high, the production capacity is small, and large-scale application cannot be realized in a short time; 3) The batch one-pot method realizes the simultaneous generation of diazomethane and olefin cyclopropanation, but increases Risks of handling diazomethane precursors.

Contents of the invention

The present invention aims to provide a method and device for continuous synthesis of cyclopropane compounds, so as to avoid the risk of pipeline transfer of diazomethane solution.

In order to achieve the above object, according to one aspect of the present invention, a method for the continuous synthesis of cyclopropane compounds is provided. The method comprises the steps of: continuously performing the synthesis reaction of the diazomethane precursor in the first reactor, the reaction product of the first reactor flows into the separator for stratification, and the organic phase obtained by stratification overflows into the second reaction In the second reactor, the diazomethane precursor is continuously consumed to prepare diazomethane, and the electron-rich monoolefin cyclopropanation reaction is carried out in situ to obtain cyclopropane compounds.

Further, the first reactor is a coil reactor or a continuous stirring reactor; the second reactor is a continuous stirring reactor or a columnar reactor.

Further, the temperature of the first reactor is controlled at -5-20°C, preferably 0-10°C; the temperature of the second reactor is controlled at 0-25°C, preferably 10-20°C.

Further, methylurea/hydrochloric acid aqueous solution, 2-methyltetrahydrofuran and sodium nitrite aqueous solution are continuously pumped into the first reactor by the first feed pump, the second feed pump and the third feed pump respectively; preferred 1.0eq of methylurea, 1.1-2.0eq of 36% concentrated hydrochloric acid, 2-8v of purified water in methylurea/hydrochloric acid aqueous solution; more preferably, 1.4-1.6eq of 36% concentrated hydrochloric acid, 3-5v of purified water; preferred , 2-methyltetrahydrofuran 10~50v, more preferably 20~30v; preferably, sodium nitrite in aqueous solution of sodium nitrite is 1.1~2.0eq, water 2~8v; more preferably, sodium nitrite is 1.4~1.6 eq, water 3~5v.

Further, the residence time of the material in the first reactor is 5-50min; preferably 15-30min; the residence time of the material in the second reactor is 10-60min, preferably 20-40min.

Further, dissolving the olefin compound and the palladium-containing catalyst in tetrahydrofuran is continuously pumped into the second reactor through the fourth feed pump, and at the same time, the potassium hydroxide aqueous solution is continuously pumped into the second reactor through the fifth feed pump; Preferably, the palladium-containing catalyst is palladium acetate; preferably, the olefin compound is 0.1-0.5eq, more preferably 0.1-0.2eq; the catalyst is 0.0005-0.005eq, more preferably 0.001-0.002eq; tetrahydrofuran is 0.5-5v, more preferably 2-3v; preferably, 2-10 eq of potassium hydroxide in the potassium hydroxide aqueous solution, more preferably; 5-20V of purified water, more preferably 5-10V.

Further, the method for the continuous synthesis of cyclopropane compounds also includes the step of post-processing the product of the second reactor; preferably, the post-processing step includes 1) leaving the reaction product in the second reactor to stand, divided into Aqueous phase and organic phase; 2) The aqueous phase is extracted with 2-methyltetrahydrofuran 5-10v, and combined with the organic phase; 3) The combined organic phase is dried with anhydrous sodium sulfate; 4) The dried organic phase is concentrated; Preferably, the olefin compound has the following structure: Wherein, R ₁ represents hydrogen, tert-butoxycarbonyl or benzyloxycarbonyl; R ₂ represents hydrogen, phenyl, methyl or pyridyl; R ₃ represents hydrogen, methyl or ethyl.

According to another aspect of the present invention, a device for continuous synthesis of cyclopropane compounds is provided. The device includes: a first reactor, which is used to continuously carry out the synthesis reaction of the diazomethane precursor; a separator, which is connected to the discharge port of the first reactor through the feed port of the separator; and the second reactor, which is set There is a feed port of the second reactor, and the feed port of the second reactor communicates with the discharge port of the separator.

Further, the first reactor is a coil reactor or a continuous stirring reactor; the second reactor is a continuous stirring reactor or a columnar reactor.

Further, the device also includes: a first solution tank for holding methylurea/hydrochloric acid aqueous solution, a second solution tank for holding 2-methyltetrahydrofuran, and a third solution for holding sodium nitrite aqueous solution tank, the fourth solution tank used to hold the tetrahydrofuran that dissolves the olefin compound and the palladium-containing catalyst, and the fifth solution tank used to hold the potassium hydroxide aqueous solution; wherein, the first solution tank, the second solution tank and the first solution tank The three solution tanks communicate with the first reactor through the first feed pump, the second feed pump and the third feed pump respectively, and the fourth solution tank and the fifth solution tank respectively pass the fourth feed pump and the fifth feed pump. The feed pump communicates with the second reactor.

Applying the technical scheme of the present invention, the diazomethane precursor (MNU) is continuously prepared in the first reactor, after the diazomethane is continuously prepared, it enters the second reactor and participates in the continuous reaction of olefin cyclopropanation in situ, which can Realize automatic control, reduce the transfer of high-risk materials, avoid the risk of pipeline transfer of diazomethane solution, and effectively improve production safety; and the equipment is simple, which can save equipment investment, and can safely and quantitatively realize the generation of diazomethane and olefin ring Simultaneously with the propanation reaction.

Description of drawings

The accompanying drawings constituting a part of the application are used to provide a further understanding of the present invention, and the schematic embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute undue limitations to the present invention. In the attached picture:

Fig. 1 shows a schematic flow chart of olefin cyclopropanation according to an embodiment of the present invention.

Detailed ways

It should be noted that, in the case of no conflict, the embodiments in the present application and the features in the embodiments can be combined with each other. The present invention will be described in detail below with reference to the accompanying drawings and examples.

Aiming at a series of technical problems existing in the prior art, the applicant develops that diazomethane precursor (MNU) is prepared continuously in the first reactor (coil pipe or continuous stirring reactor), and in the second reactor (continuous stirring reactor) A continuous process in which diazomethane precursors are consumed continuously in a reactor or a column reactor) to prepare diazomethane and an electron-rich monoolefin cyclopropanation reaction is carried out in situ. In a typical embodiment, the main chemical reactions are as follows:

Wherein, R ₁ = hydrogen, tert-butoxycarbonyl, R ₁ represents hydrogen, tert-butoxycarbonyl or benzyloxycarbonyl; R ₂ represents hydrogen, phenyl, methyl or pyridyl; R ₃ represents hydrogen, methyl or ethyl .

According to a typical embodiment of the present invention, a method for continuously synthesizing cyclopropane compounds is provided. The method comprises the steps of: continuously performing the synthesis reaction of the diazomethane precursor in the first reactor, the reaction product of the first reactor flows into the separator for stratification, and the organic phase obtained by stratification overflows into the second reaction In the second reactor, the diazomethane precursor is continuously consumed to prepare diazomethane, and the electron-rich monoolefin cyclopropanation reaction is carried out in situ to obtain cyclopropane compounds.

Applying the technical scheme of the present invention, the diazomethane precursor (MNU) is continuously prepared in the first reactor, after the diazomethane is continuously prepared, it enters the second reactor and participates in the continuous reaction of olefin cyclopropanation in situ, which can Realize automatic control, reduce the transfer of high-risk materials, avoid the risk of pipeline transfer of diazomethane solution, and effectively improve production safety; and the equipment is simple, which can save equipment investment, and can safely and quantitatively realize the generation of diazomethane and olefin ring Simultaneously with the propanation reaction.

Because the first-stage reaction in the first reactor is a two-phase solution reaction, a coil with better airtightness can be used, and a continuously stirred reactor can also be used, which is conducive to a two-phase reaction. The second stage reaction in the second reactor is also a two-phase solution reaction. The difference is that there is gas released during the reaction, which is not conducive to mixing. It is not suitable for coil reactors. Both continuous stirring reactors and column reactors can In the case of release, ensure the mixing effect of the reaction solution.

If the temperature is too low, there will be precipitation, which will affect fluidity; if the temperature is too high, it will affect the stability of the product in the first reactor. Therefore, preferably, the temperature of the first reactor is controlled at -5 ~ 20 ° C, more preferably 0 ~ 10°C. The temperature of the second reactor is controlled at 0-25°C, preferably 10-20°C.

In order to realize continuous automatic generation conveniently, in a typical embodiment of the present invention, methyl urea/hydrochloric acid aqueous solution, 2-methyltetrahydrofuran are fed respectively by the first feed pump, the second feed pump and the third feed pump and sodium nitrite aqueous solution are continuously pumped into the first reactor;

Preferably, in methylurea/hydrochloric acid aqueous solution, methylurea 1.0eq, 36% concentrated hydrochloric acid 1.1～2.0eq, purified water 2～8v; more preferably, 36% concentrated hydrochloric acid 1.4～1.6eq, purified water 3～5v ( Among them, here v refers to the volume relative to methyl urea, for example, feeding 1g of methyl urea, 3~5v purified water means that the amount of purified water is 3~5ml); this can ensure the fluidity of the solution, and will not Too much solvent will affect the reaction effect.

In order to ensure the smooth and efficient reaction, preferably, 2-methyltetrahydrofuran is 10-50v, more preferably 20-30v; preferably, the sodium nitrite in the sodium nitrite aqueous solution is 1.1-2.0eq, and the water is 2-8v; More preferably, the sodium nitrite is 1.4-1.6eq, and the water is 3-5v.

In order to fully react the materials, the residence time of the materials in the first reactor is 5-50 min; preferably 15-30 min; the residence time of the materials in the second reactor is 10-60 min, preferably 20-40 min.

In a typical embodiment of the present invention, olefin compound and palladium-containing catalyst are dissolved in tetrahydrofuran and continuously pumped into the second reactor through the fourth feed pump, and potassium hydroxide aqueous solution is continuously pumped through the fifth feed pump into the second reactor; preferably, the palladium-containing catalyst is palladium acetate; preferably, the olefin compound is 0.1 to 0.5eq, more preferably 0.1 to 0.2eq; the catalyst is 0.0005 to 0.005eq, more preferably 0.001 to 0.002eq; tetrahydrofuran 0.5-5v, more preferably 2-3v; preferably, 2-10eq of potassium hydroxide in aqueous potassium hydroxide solution, more preferably; purified water 5-20V, more preferably 5-10V. Thereby ensuring the efficient progress of the reaction.

According to a typical embodiment of the present invention, the method for continuously synthesizing cyclopropane compounds also includes the step of post-processing the product of the second reactor; preferably, the post-processing step includes: 1) converting the second reaction The reaction product in the container is left standing, and is divided into an aqueous phase and an organic phase; 2) the aqueous phase is extracted with 2-methyltetrahydrofuran 5-10v, and combined with the organic phase; 3) the combined organic phase is extracted with anhydrous Dry over sodium sulfate; 4) Concentrate the dried organic phase.

According to a typical embodiment of the present invention, a device for continuous synthesis of cyclopropane compounds is provided. The device comprises: a first reactor for continuously carrying out the synthesis reaction of the diazomethane precursor, a separator communicated with the discharge port of the first reactor through the feed port of the separator, and a second reactor, the first The second reactor is provided with a feed port of the second reactor, and the feed port of the second reactor communicates with the discharge port of the separator. The above-mentioned technical solution can be realized by adopting the device.

Preferably, the first reactor is a coil reactor or a continuous stirring reactor; the second reactor is a continuous stirring reactor or a columnar reactor.

Preferably, the device also includes: a first solution tank for holding methylurea/hydrochloric acid aqueous solution, a second solution tank for holding 2-methyltetrahydrofuran, and a third solution for holding sodium nitrite aqueous solution tank, the fourth solution tank used to hold the tetrahydrofuran that dissolves the olefin compound and the palladium-containing catalyst, and the fifth solution tank used to hold the potassium hydroxide aqueous solution; wherein, the first solution tank, the second solution tank and the first solution tank The three solution tanks communicate with the first reactor through the first feed pump, the second feed pump and the third feed pump respectively, and the fourth solution tank and the fifth solution tank respectively pass the fourth feed pump and the fifth feed pump. The feed pump communicates with the second reactor.

The beneficial effects of the present invention will be further described below in conjunction with examples.

Example 1

Olefin compounds:

Continuous reaction: See Table 1 for the feed pump speed and reaction parameters statistics, and the schematic diagram of the reaction process is shown in Figure 1.

(1) Prepare the solution: add 370g of purified water and 82.5g of N-methylurea to a 2L Erlenmeyer flask, stir until fully dissolved, then slowly add 190g of concentrated hydrochloric acid (mass fraction: 36%), stir evenly and set aside (methylurea urea/hydrochloric acid solution). Add 370g of purified water into the 1L Erlenmeyer flask, add 130g of solid sodium nitrite, stir until fully dissolved (sodium nitrite aqueous solution), and set aside. Add 250ml 2-methyltetrahydrofuran, 50g olefin compound (20.38mmol), and 0.4g palladium acetate to a 1L conical flask, stir until completely dissolved, and set aside (olefin/catalyst solution). Add 600g purified water in 1L Erlenmeyer flask, add 210g potassium hydroxide in batches, stir until fully dissolved, stand-by (potassium hydroxide solution).

(2) Control the temperature of the first reactor 10 to 0-10°C, and control the temperature of the second reactor 20 to 10-20°C. Simultaneously start the first feed pump P-1 (methylurea/hydrochloric acid solution) and the second Pump P-2 (2-methyltetrahydrofuran), and later turn on the third feeding pump P-3 (sodium nitrite aqueous solution), so that three streams of materials enter the first reactor 10 at the same time. The reaction system enters the separator 30 from the first reactor 10 for stratification. When an organic phase enters the second reactor 20, open the fourth feed pump P-4 (alkene/catalyst solution) and the fifth feed pump P-5 (potassium hydroxide solution), after 30min, from the second reactor 20 in-samples to track response effects. The system in the second reactor 20 is subjected to liquid separation, filtration, concentration and other operations to obtain the cyclopropane product (entering the receiving tank), with a yield of 82%. From the start of feeding to the end of feeding, the entire operation time is ~4h.

Table 1

Comparative example 1

Batch response:

(1) Under nitrogen protection, add 135g of purified water, 16.5g of N-methylurea, and 26g of solid sodium nitrite into a 2L four-neck flask (mechanical stirring), and stir until completely dissolved. Then add 400g of 2-methyltetrahydrofuran to the four-necked bottle, cool the system to 0-10°C, slowly add 38g of concentrated hydrochloric acid (mass fraction: 36%) dropwise to the four-necked bottle through the constant pressure dropping funnel, dropwise During the process, if the solid precipitates and does not dissolve quickly, stop the dropwise addition, and then continue the dropwise addition after the solid dissolves. The entire dropwise addition process lasts for 1 hour. After the dropwise addition is completed, keep stirring for 20-30 minutes, let stand for liquid separation, and the organic phase will be used for subsequent reactions.

(2) Under the protection of nitrogen, stir evenly into another 1L four-neck flask and add 50ml of tetrahydrofuran, 10g of olefin compound, 0.4g of palladium acetate, stir until completely dissolved, and set aside. Add the pre-prepared potassium hydroxide aqueous solution (potassium hydroxide 42g, purified water 120g), lower the temperature to 10-20°C, add the organic phase in operation (1) dropwise to the 1L four-necked bottle, and release gas when the dropwise addition is started The speed is fast, reduce the feeding speed, control the dropping speed throughout the dropping process to make the gas release gentle, and increase the dropping speed in the later stage, keep warm for 30 minutes after the dropping, and take samples to test the reaction effect. The whole dropping process takes about 2.5h. The system undergoes liquid separation, filtration, concentration and other operations to obtain the cyclopropane product.

Typical sample: olefin feedstock, 1.8% cyclopropane product, 85.2%; yield 83%.

Example 2

The difference from Example 1 is: the temperature of the first reactor is controlled at 30-35°C. Typical sample: olefin feedstock, 18.8% cyclopropane product, 65.2%; yield 63%.

Example 3

The difference with Example 1 is: the residence time of the first reactor is 5min. Typical sample: olefin feedstock, 8.2% cyclopropane product, 75.2%; yield 73%.

Example 4

The difference from Example 1 is: the amount of 2-methyltetrahydrofuran is 50v. Typical sample: olefin feedstock, 5.7% cyclopropane product, 78.2%; yield 77%.

Example 5

The difference from Example 1 is: the temperature of the second reactor is controlled at 30-35°C. Typical sample: olefin feedstock, 34.8% cyclopropane product, 52.2%; yield 47%.

Example 6

The difference with Example 1 is: the residence time of the second reactor is 10min. Typical sample: olefin feedstock, 6.2% cyclopropane product, 83.9%; yield 81%.

Example 7

Olefin compounds:

Continuous reaction, embodiment is the same as Example 1, typical sample: olefin raw material, 0.9% cyclopropane product, 88.2%; Yield 84%.

Example 8

Olefin compounds:

Continuous reaction, embodiment is the same as Example 1, typical sample: olefin raw material, 2.2% cyclopropane product, 84.2%; Yield 80%.

Example 9

Olefin compounds:

Continuous reaction, embodiment is the same as Example 1, typical sample: olefin raw material, 0.7% cyclopropane product, 86.2%; Yield 84%.

The above descriptions are only preferred embodiments of the present invention, and are not intended to limit the present invention. For those skilled in the art, the present invention can have various modifications and changes. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention shall be included within the protection scope of the present invention.

Claims (10)

1. a method for the continuous synthesis of cyclopropane compounds, is characterized in that, comprises the following steps: in the first reactor, carry out the synthetic reaction of diazomethane precursor continuously, the reaction product of described first reactor flows into separator Stratification is carried out in , and the organic phase obtained by stratification overflows into the second reactor, in which the diazomethane precursor is continuously consumed to prepare diazomethane and electron-rich monoolefin cyclopropane is carried out in situ Chemical reaction obtains described cyclopropane compounds. 2. The method according to claim 1, characterized in that, the first reactor is a coil reactor or a continuous stirring reactor; the second reactor is a continuous stirring reactor or a columnar reactor. 3. The method according to claim 1, characterized in that, the temperature of the first reactor is controlled at -5～20°C, preferably 0～10°C; the temperature of the second reactor is controlled at 0～20°C. 25°C, preferably 10-20°C. 4. method according to claim 1 is characterized in that, methylurea/hydrochloric acid aqueous solution, 2-methyltetrahydrofuran and nitrous acid are respectively passed through the first feed pump, the second feed pump and the 3rd feed pump An aqueous sodium solution is continuously pumped into the first reactor; Preferably, in the methylurea/hydrochloric acid aqueous solution, 1.0 eq of methyl urea, 1.1-2.0 eq of 36% concentrated hydrochloric acid, 2-8 v of purified water; more preferably, 1.4-1.6 eq of 36% concentrated hydrochloric acid, 3-3 eq of purified water 5v; Preferably, the 2-methyltetrahydrofuran is 10-50v, more preferably 20-30v; Preferably, the sodium nitrite in the sodium nitrite aqueous solution is 1.1-2.0 eq, and the water is 2-8 v; more preferably, the sodium nitrite is 1.4-1.6 eq, and the water is 3-5 v. 5. The method according to claim 4, characterized in that, the residence time of the material in the first reactor is 5 to 50 min; preferably 15 to 30 min; the residence time of the material in the second reactor 10 to 60 minutes, preferably 20 to 40 minutes. 6. The method according to claim 1, characterized in that, the olefinic compound and the palladium-containing catalyst are dissolved in tetrahydrofuran and are continuously pumped into the second reactor by the fourth feed pump, while potassium hydroxide aqueous solution is passed through a fifth feed pump continuously pumps into said second reactor; Preferably, the palladium-containing catalyst is palladium acetate; Preferably, the olefin compound is 0.1-0.5eq, more preferably 0.1-0.2eq; the catalyst is 0.0005-0.005eq, more preferably 0.001-0.002eq; tetrahydrofuran is 0.5-5v, more preferably 2-3v; Preferably, the potassium hydroxide in the aqueous potassium hydroxide solution is 2-10 eq, more preferably; 5-20 V of purified water, more preferably 5-10 V. 7. The method according to claim 6, characterized in that, the method for the continuous synthesis of cyclopropane compounds also includes the step of post-processing the product of the second reactor; Preferably, the post-treatment step includes 1) standing the reaction product in the second reactor, and dividing it into an aqueous phase and an organic phase; 2) extracting the aqueous phase with 5-10v of 2-methyltetrahydrofuran , combined with the organic phase; 3) drying the combined organic phase with anhydrous sodium sulfate; 4) concentrating the dried organic phase; Preferably, the olefin compound has the following structure: Wherein, R ₁ represents hydrogen, tert-butoxycarbonyl or benzyloxycarbonyl; R ₂ represents hydrogen, phenyl, methyl or pyridyl; R ₃ represents hydrogen, methyl or ethyl. 8. A device for the continuous synthesis of cyclopropane compounds, characterized in that it comprises: The first reactor is used to continuously carry out the synthesis reaction of diazomethane precursor; a separator, communicated with the discharge port of the first reactor through the feed port of the separator; and The second reactor is provided with a feed port of the second reactor, and the feed port of the second reactor communicates with the discharge port of the separator. 9. The device according to claim 8, characterized in that, the first reactor is a coil reactor or a continuous stirring reactor; the second reactor is a continuous stirring reactor or a columnar reactor. 10. device according to claim 8, is characterized in that, described device also comprises: the first solution tank that is used to hold methylurea/hydrochloric acid aqueous solution, is used to hold the second solution of 2-methyltetrahydrofuran tanks, a third solution tank for containing an aqueous solution of sodium nitrite, a fourth solution tank for containing dissolved olefinic compound and tetrahydrofuran containing a palladium catalyst, and a fifth solution tank for containing an aqueous solution of potassium hydroxide ; wherein, the first solution tank, the second solution tank and the third solution tank communicate with the first reactor through the first feed pump, the second feed pump and the third feed pump respectively, and the The fourth solution tank and the fifth solution tank communicate with the second reactor through the fourth feed pump and the fifth feed pump respectively.