CN116253672A - Synthesis method of 1-Boc-3-chlorosulfonyl pyrrolidine - Google Patents

Abstract

The invention discloses a synthesis method of 1-Boc-3-chlorosulfonyl pyrrolidine, which comprises the steps of obtaining light yellow oily matter by using 1-Boc-3-hydroxypyrrolidine, a first reaction solvent, organic base and substituted sulfonyl chloride; dissolving the light yellow oily matter in a second reaction solvent and reacting with thioacetate to obtain yellow oily matter; the yellow oil was dissolved in a third reaction solvent and reacted by passing a displacement gas to give a light brown oil, i.e., 1-Boc-3-chlorosulfonylpyrrolidine. The invention can obtain the 1-Boc-3-chlorosulfonyl pyrrolidine through easily available raw materials and simple process steps.

Description

A kind of synthetic method of 1-Boc-3-chlorosulfonylpyrrolidine

technical field

The invention relates to a synthesis method of 1-Boc-3-chlorosulfonylpyrrolidine, which belongs to the technical field of pharmaceutical and chemical synthesis.

Background technique

Na channels are at the heart of action potential generation in all excitable cells, including neurons and muscle cells, which play an important role in excitable tissues, including brain, gastrointestinal smooth muscle, skeletal muscle, peripheral Nervous system, spinal cord and airways. As such, they play an important role in various disease states such as epilepsy, pain, myotonia, ataxia. Multiple sclerosis, irritable bowel, urinary incontinence and visceral pain as well as a range of psychiatric dysfunctions such as anxiety and depression.

Compounds of the general formula I have now been found to act as voltage-gated sodium channel inhibitors:

Such compounds and pharmaceutically acceptable compositions are useful in the treatment or alleviation of other severity of a variety of diseases, disorders or conditions including, but not limited to, acute, chronic, neuropathic or inflammatory pain, arthritis, migraine, cluster Headache, trigeminal neuralgia, herpetic neuralgia, generalized neuralgia, epilepsy or epilepsy, neurodegenerative disorders, psychiatric disorders such as anxiety and depression, myotonia, cardiac arrhythmias, movement disorders, neuroendocrine disorders, ataxia , multiple sclerosis, irritable bowel syndrome, incontinence, visceral pain, osteoarthritis pain, postherpetic neuralgia, diabetic neuropathy, nerve root pain, sciatica, back pain, head or neck pain, severe or intractable Pain, nociceptive pain, breakthrough pain, postoperative pain, or cancer pain.

It can be seen that this type of compound is a very promising drug prodrug molecule, but the existing 1-Boc-3-chlorosulfonylpyrrolidine synthesis technology has problems such as high cost, high process difficulty, and inconvenient mass production.

Contents of the invention

The purpose of the present invention is to overcome the deficiencies in the prior art and provide a synthetic method for 1-Boc-3-chlorosulfonylpyrrolidine, which can obtain 1-Boc-3-chloro Sulfonylpyrrolidine.

In order to achieve the above object, the present invention is achieved by adopting the following technical solutions:

The present invention provides a kind of synthetic method of 1-Boc-3-chlorosulfonylpyrrolidine, comprising the following steps:

Using 1-Boc-3-hydroxypyrrolidine, the first reaction solvent, an organic base and a substituted sulfuryl chloride to obtain a light yellow oil;

The light yellow oil was dissolved in the second reaction solvent, and reacted with thioacetate to obtain a yellow oil;

The yellow oil was dissolved in the third reaction solvent, and passed through a replacement gas for reaction to obtain a light brown oil, namely 1-Boc-3-chlorosulfonylpyrrolidine.

Further, the use of 1-Boc-3-hydroxypyrrolidine, the first reaction solvent, an organic base and a substituted sulfonyl chloride to obtain a light yellow oily substance includes:

After dissolving 1-Boc-3-hydroxypyrrolidine in the first reaction solvent, add the organic base dropwise to the first mixed solution while stirring, after the drop is completed, cool the first mixed solution to -20～30°C;

Add substituted sulfonyl chloride dropwise to the first mixed solution, after the drop is complete, warm the first mixed solution to room temperature, and let it stand for reaction for more than 2 hours;

After washing the first mixed solution with hydrochloric acid, aqueous sodium bicarbonate solution, and brine in sequence, the first mixed solution was dried and concentrated to obtain a light yellow oil.

Further, the use of 1-Boc-3-hydroxypyrrolidine, the first reaction solvent, an organic base and a substituted sulfonyl chloride to obtain a light yellow oily substance includes:

The first reaction solvent is dichloromethane solvent;

The organic base is selected from one of triethylamine, diisopropylethylamine and pyridine;

The substituted sulfonyl chloride is selected from one of methanesulfonyl chloride, trifluoromethanesulfonyl chloride and toluenesulfonyl chloride.

Further, the use of 1-Boc-3-hydroxypyrrolidine, the first reaction solvent, an organic base and a substituted sulfonyl chloride to obtain a light yellow oily substance includes:

The mass volume ratio of the 1-Boc-3-hydroxypyrrolidine to the first reaction solvent is 1g: (3-20)mL;

The equivalent ratio of the 1-Boc-3-hydroxypyrrolidine to the organic base is less than or equal to 1/2;

The equivalent ratio of the 1-Boc-3-hydroxypyrrolidine to the substituted sulfonyl chloride is 1:(1-4).

Further, dissolving the light yellow oil in the second reaction solvent and reacting with thioacetate to obtain the yellow oil includes:

Take the light yellow oil, and dissolve the light yellow oil in the second reaction solvent;

After adding thioacetate to the second mixed solution, raise the temperature of the second mixed solution to 40-100°C, and let it stand for reaction for more than 1 hour;

Dilute the second mixed solution with deionized water, extract with methyl tert-butyl ether sequentially, wash the diluted second mixed solution with aqueous sodium chloride, dry and concentrate the second mixed solution to obtain a yellow oil.

Further, dissolving the light yellow oil in the second reaction solvent and reacting with thioacetate to obtain the yellow oil includes:

Described thioacetate is selected from the one in potassium thioacetate, sodium thioacetate, lithium thioacetate;

The second reaction solvent is selected from one of N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone.

Further, dissolving the light yellow oil in the second reaction solvent and reacting with thioacetate to obtain the yellow oil includes:

The equivalent ratio of the second reaction solvent to the light yellow oil is greater than or equal to 1;

The mass volume ratio of the light yellow oil to the second reaction solvent was 1 g:5 mL.

Further, the yellow oily substance is dissolved in the third reaction solvent, and passed through a replacement gas for reaction, and the light brown oily substance obtained includes:

Take the light brown oil, dissolve the light brown oil in the third reaction solvent, and cool the third mixed solution to -20～20°C;

Pass replacement gas into the third mixed liquid, keep the temperature of the third mixed liquid below 0°C, and let it stand for reaction for more than 1 hour;

Dilute the third mixed solution with the first deionized water, wash the third mixed solution with sodium chloride aqueous solution and the second deionized water in sequence, and concentrate the third mixed solution to obtain a light brown oil.

Further, the yellow oily substance is dissolved in the third reaction solvent, and passed through a replacement gas for reaction, and the light brown oily substance obtained includes:

The replacement gas is chlorine or sulfuryl chloride;

The third reaction solvent is selected from one of dichloromethane solvent, ethyl acetate, ethanol, methanol, and tetrahydrofuran.

Further, the yellow oily substance is dissolved in the third reaction solvent, and passed through a replacement gas for reaction, and the light brown oily substance obtained includes:

The mass volume ratio of the yellow oil to the third reaction solvent is 1g:10mL;

The volume ratio of the third reaction solvent, the first deionized water, sodium chloride aqueous solution, and the second deionized water is 1:1:1:1;

The equivalent ratio of the replacement gas to the yellow oil is greater than or equal to 3.

Compared with the prior art, the beneficial effects achieved by the present invention are as follows:

The raw materials used in the present invention are low in cost and easy to obtain, and there is no cryogenic operation in the technical process, and no special production equipment is required, which is convenient for industrial scale-up production; the synthetic route of the present invention is short, the yield is high, and 1-Boc- 3-Chlorosulfonylpyrrolidine.

Detailed ways

The present invention will be further described below. The following examples are only used to illustrate the technical solution of the present invention more clearly, but not to limit the protection scope of the present invention.

In describing the present invention, it should be understood that the terms "center", "longitudinal", "transverse", "upper", "lower", "front", "rear", "left", "right", " The orientations or positional relationships indicated by "vertical", "horizontal", "top", "bottom", "inner" and "outer" are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying No device or element must have a specific orientation, be constructed, and operate in a specific orientation and therefore should not be construed as limiting the invention. In addition, the terms "first", "second", etc. are used for descriptive purposes only, and should not be understood as indicating or implying relative importance or implicitly specifying the quantity of the indicated technical features. Thus, a feature defined as "first", "second", etc. may expressly or implicitly include one or more of that feature. In the description of the present invention, unless otherwise specified, "plurality" means two or more.

In the description of the present invention, it should be noted that unless otherwise specified and limited, the terms "installation", "connection" and "connection" should be understood in a broad sense, for example, it can be a fixed connection or a detachable connection. Connected, or integrally connected; it may be mechanically connected or electrically connected; it may be directly connected or indirectly connected through an intermediary, and it may be the internal communication of two components. Those of ordinary skill in the art can understand the specific meanings of the above terms in the present invention based on specific situations.

In the present invention, 1-Boc-3-hydroxypyrrolidine 1 is used as raw material to synthesize 1-Boc-3-methylsulfonyloxypyrrolidine 2 with substituted sulfuryl chloride, and then 1-Boc-3 is synthesized with thioacetate -Methanesulfonylpyrrolidine 3, finally synthesize 1-Boc-3-chlorosulfonylpyrrolidine 4 with displacement gas, the specific synthetic route is as follows:

The purity of 1-Boc-3-chlorosulfonylpyrrolidine 4 obtained in this application through the synthetic route is as high as 97%.

The synthetic method of 1-Boc-3-chlorosulfonylpyrrolidine of the present application is a three-step method, specifically as follows:

S1 Use 1-Boc-3-hydroxypyrrolidine, the first reaction solvent, organic base and substituted sulfuryl chloride to obtain a light yellow oil.

When applied, step S1 includes steps S11-S13, specifically as follows:

S11 After dissolving 1-Boc-3-hydroxypyrrolidine in the first reaction solvent, add an organic base dropwise to the first mixed solution while stirring, after the drop is complete, cool the first mixed solution to -20-30°C, Preferably, the first mixed liquid is cooled to 0-5°C.

S12 Add substituted sulfonyl chloride dropwise to the first mixed solution. After the drop is complete, warm the first mixed solution to room temperature, and let it stand for reaction for more than 2 hours.

S13 Wash the first mixed solution with hydrochloric acid, aqueous sodium bicarbonate solution, and brine in sequence, then dry and concentrate the first mixed solution to obtain a light yellow oil.

In actual application, the first reaction solvent is dichloromethane solvent; the organic base is selected from triethylamine, diisopropylethylamine, and pyridine, preferably, the organic base is triethylamine; the substituted sulfonyl chloride is selected from One of methanesulfonyl chloride, trifluoromethanesulfonyl chloride and toluenesulfonyl chloride, preferably, the substituted sulfuryl chloride is methanesulfonyl chloride.

The mass volume ratio of 1-Boc-3-hydroxypyrrolidine in step S1 of the present invention to the first reaction solvent is 1g: (3-20) mL, preferably, 1-Boc-3-hydroxypyrrolidine and the first reaction solvent The mass volume ratio of the solvent is 1g: 10mL; the equivalent ratio of 1-Boc-3-hydroxypyrrolidine to organic base is less than or equal to 1/2, preferably, the equivalent ratio of 1-Boc-3-hydroxypyrrolidine to organic base is equal to 1/2; The equivalent ratio of 1-Boc-3-hydroxypyrrolidine to substituted sulfonyl chloride is 1:(1~4), preferably, the equivalent ratio of 1-Boc-3-hydroxypyrrolidine to substituted sulfonyl chloride is 1 :1.2; the volume ratio of the first reaction solvent, hydrochloric acid, sodium bicarbonate aqueous solution, and saline is 2:1:1:1.

S2 Dissolve the light yellow oil in the second reaction solvent and react with thioacetate to obtain a yellow oil.

During application, step S2 includes steps S21-S23, specifically as follows:

S21 Take the light yellow oil, and dissolve the light yellow oil in the second reaction solvent.

S22 After adding thioacetate to the second mixed solution, raise the temperature of the second mixed solution to 40-100° C., and let it stand for reaction for more than 1 hour. Preferably, raise the temperature of the second mixed solution to 60-70° C., and Let it stand for more than 1h.

S23 Dilute the second mixed solution with deionized water, extract with methyl tert-butyl ether sequentially, wash the diluted second mixed solution with aqueous sodium chloride solution, dry and concentrate the second mixed solution to obtain a yellow oil.

In actual application, the thioacetate is selected from one of potassium thioacetate, sodium thioacetate, and lithium thioacetate, preferably, the =thioacetate is potassium thioacetate; the second reaction solvent is selected from One of N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone, preferably, the second reaction solvent is N,N-dimethylformamide;

The equivalent ratio of the second reaction solvent to the light yellow oil in the step S2 of the present invention is greater than or equal to 1, preferably, the equivalent ratio of the second reaction solvent to the light yellow oil is equal to 1.2; the ratio of the light yellow oil to the second reaction solvent The mass volume ratio is 1g:5mL; the volume ratio of the second reaction solvent, deionized water, methyl tert-butyl ether, and sodium chloride aqueous solution is 1:2:1:1.

S3 Dissolve the yellow oil in the third reaction solvent, and pass through the replacement gas for reaction to obtain a light brown oil, namely 1-Boc-3-chlorosulfonylpyrrolidine.

During application, step S3 includes steps S31-S33, specifically as follows:

S31 Take the light brown oil, dissolve the light brown oil in the third reaction solvent, then cool the third mixed liquid to -20-20°C, preferably, cool the third mixed liquid to -10-0°C.

S32 injecting replacement gas into the third mixed liquid, keeping the temperature of the third mixed liquid below 0° C., and standing for reaction for more than 1 h.

S33 Dilute the third mixed solution with the first deionized water, wash the third mixed solution with sodium chloride aqueous solution and the second deionized water in sequence, and concentrate the third mixed solution to obtain a light brown oil.

In actual application, the replacement gas is chlorine or sulfonyl chloride, preferably, the replacement gas is chlorine; the third reaction solvent is selected from one of dichloromethane solvent, ethyl acetate, ethanol, methanol, tetrahydrofuran, preferably, the third The reaction solvent is dichloromethane solvent.

The mass volume ratio of the yellow oil in step S3 of the present invention to the third reaction solvent is 1g:10mL; the equivalent ratio of the replacement gas to the yellow oil is greater than or equal to 3, preferably, the equivalent of the replacement gas to the yellow oil is equal to 4; The volume ratio of the third reaction solvent, the first deionized water, the sodium chloride aqueous solution and the second deionized water is 1:1:1:1.

Example 1

This example describes in detail a synthetic method of 1-Boc-3-chlorosulfonylpyrrolidine.

The synthetic method of present embodiment 1-Boc-3-chlorosulfonylpyrrolidine is specifically as follows:

Step 1: Synthesis of 1-Boc-3-methanesulfonyloxypyrrolidine: use 1-Boc-3-hydroxypyrrolidine, the first reaction solvent, organic base and substituted sulfonyl chloride to obtain light yellow oil.

When applying, the specific operation of step 1 is as follows:

S11 After dissolving 1-Boc-3-hydroxypyrrolidine in the first reaction solvent, add the organic base dropwise to the first mixed solution while stirring, and after the dropping is complete, cool the first mixed solution to 0-5°C.

In actual application, first, 30.0 g of 1-Boc-3-hydroxypyrrolidine was added to 300 mL of dichloromethane to dissolve, and the 1-Boc-3-hydroxypyrrolidine at this time was 160 mmol; then, while stirring the first While slowly adding 32.4 g of triethylamine to the mixed solution, the triethylamine at this time is 320 mmol; protect with nitrogen, and cool down the first mixed solution to 0-5°C.

S12 Add substituted sulfonyl chloride dropwise to the first mixed solution. After the drop is complete, warm the first mixed solution to room temperature, and let it stand for reaction for more than 2 hours.

In actual application, 22.0 g of methanesulfonyl chloride was slowly added dropwise to the first mixed solution, and the methanesulfonyl chloride at this time was 192 mmol. After the addition was completed, the temperature was slowly raised to room temperature, and reacted at room temperature for 2 hours.

S13 Wash the first mixed solution with hydrochloric acid, aqueous sodium bicarbonate solution, and brine in sequence, then dry and concentrate the first mixed solution to obtain a light yellow oil.

In actual application, wash once with 150mL 1M hydrochloric acid, once with 150mL saturated aqueous sodium bicarbonate solution, once with 150mL saturated brine, then dry with sodium sulfate, filter, and concentrate the filtrate at 45°C to obtain 40.4g of light yellow oil. The purity of 1-Boc-3-methanesulfonyloxypyrrolidine in Example was 98A%, and the corrected yield was 95%.

Step 2: Synthesis of 1-Boc-3-acetylmercaptopyrrolidine: the light yellow oil was dissolved in the second reaction solvent and reacted with thioacetate to obtain a yellow oil.

When applying, the specific operation of step 2 is as follows:

S21 Take the light yellow oil, and dissolve the light yellow oil in the second reaction solvent.

In actual application, take 34.0g of light yellow oil, that is, 128mmol of 1-Boc-3-methanesulfonyloxypyrrolidine, and add the light yellow oil to 170mL of N,N-dimethylformamide to dissolve .

S22 After adding thioacetate to the second mixed solution, the temperature of the second mixed solution is raised to 60-70° C., and left to react for more than 1 hour.

In actual application, 17.6 g of potassium thioacetate was added to the second mixed solution, and the potassium thioacetate at this time was 154 mmol. The temperature of the second mixed solution was raised to 60-70° C. and allowed to stand for reaction for 1 hour.

S23 Dilute the second mixed solution with deionized water, extract with methyl tert-butyl ether sequentially, wash the diluted second mixed solution with aqueous sodium chloride solution, dry and concentrate the second mixed solution to obtain a yellow oil.

In actual application, the second mixed solution starts to solidify, dilute the second mixed solution with 340mL deionized water, then extract 3 times with 170mL methyl tert-butyl ether, then wash 4 times with 170mL saturated aqueous sodium chloride solution, and wash with anhydrous After drying over sodium sulfate, the filtrate was concentrated at 45°C to obtain 27.3 g of a yellow oil. The purity of 1-Boc-3-acetylmercaptopyrrolidine in this example is 95A%, and the corrected yield is 87%.

Step 3: Synthesis of 1-Boc-3-chlorosulfonylpyrrolidine: Dissolve the yellow oil in the third reaction solvent, and pass through the replacement gas for reaction to obtain a light brown oil, namely 1-Boc-3-chloro Sulfonylpyrrolidine.

When applying, the specific operation of step 3 is as follows:

S31 Take the light brown oil, dissolve the light brown oil in the third reaction solvent, and then cool the third mixed liquid to -10～0°C.

During practical application, 25.0g 1-Boc-3-acetylmercaptopyrrolidine was added to 250mL of dichloromethane to dissolve, and the 1-Boc-3-acetylmercaptopyrrolidine at this moment was 102mmol, and the third mixed solution was cooled to -10～0℃.

S32 injecting replacement gas into the third mixed liquid, keeping the temperature of the third mixed liquid below 0° C., and standing for reaction for more than 1 h.

In actual application, 28.9 g of chlorine gas is slowly introduced into the third mixed solution for 1 hour, and the chlorine gas at this time is 408 mmol, and the temperature of the third mixed solution is kept below 0°C.

S33 Dilute the third mixed solution with the first deionized water, wash the third mixed solution with sodium chloride aqueous solution and the second deionized water in sequence, and concentrate the third mixed solution to obtain a light brown oil.

In actual application, add 250mL of the first deionized water to the third mixed solution to separate the layers of the third mixed solution, wash the dichloromethane layer with 250mL of the second deionized water once, and wash with 250mL of saturated sodium chloride aqueous solution for 1 times, and then concentrated to give 20.6 g of light brown oil. The purity of 1-Boc-3-chlorosulfonylpyrrolidine in this example is 97A%, and the corrected yield is 75%.

In summary, it can be seen from the above examples that the raw materials used in the present invention have low cost and are easy to obtain, and the technical process does not require cryogenic operation, and does not require special production equipment, which is convenient for industrial scale-up production; the synthetic route of the present invention is short, the yield is high, and the obtained 1- Boc-3-chlorosulfonylpyrrolidine has high chemical purity.

The above is only a preferred embodiment of the present invention, and it should be pointed out that for those of ordinary skill in the art, without departing from the technical principle of the present invention, some improvements and modifications can also be made. It should also be regarded as the protection scope of the present invention.

Claims (10)

1. The synthesis method of the 1-Boc-3-chlorosulfonyl pyrrolidine is characterized by comprising the following steps of:

obtaining a pale yellow oil by using 1-Boc-3-hydroxypyrrolidine, a first reaction solvent, an organic base and substituted sulfonyl chloride;

dissolving the light yellow oily matter in a second reaction solvent and reacting with thioacetate to obtain yellow oily matter;

the yellow oil was dissolved in a third reaction solvent and reacted by passing a displacement gas to give a light brown oil, i.e., 1-Boc-3-chlorosulfonylpyrrolidine.

2. The method for synthesizing 1-Boc-3-chlorosulfonylpyrrolidine according to claim 1, wherein the obtaining of a pale yellow oil using 1-Boc-3-hydroxypyrrolidine, the first reaction solvent, the organic base, and the substituted sulfonyl chloride comprises:

after 1-Boc-3-hydroxypyrrolidine is dissolved in a first reaction solvent, dropwise adding organic alkali into the first mixed solution while stirring, and cooling the first mixed solution to-20-30 ℃ after the dropwise adding;

dropwise adding substituted sulfonyl chloride into the first mixed solution, after the dropwise adding, heating the first mixed solution to room temperature, and standing for more than 2 hours for reaction;

the first mixed solution was washed with hydrochloric acid, an aqueous sodium hydrogencarbonate solution and brine in this order, and then dried and concentrated to obtain a pale yellow oily substance.

3. The method for synthesizing 1-Boc-3-chlorosulfonylpyrrolidine according to claim 2, wherein the obtaining of a pale yellow oil using 1-Boc-3-hydroxypyrrolidine, the first reaction solvent, the organic base, and the substituted sulfonyl chloride comprises:

the first reaction solvent is a dichloromethane solvent;

the organic base is selected from one of triethylamine, diisopropylethylamine and pyridine;

the substituted sulfonyl chloride is selected from one of methanesulfonyl chloride, trifluoromethanesulfonyl chloride and toluenesulfonyl chloride.

4. The method for synthesizing 1-Boc-3-chlorosulfonylpyrrolidine according to claim 2, wherein the obtaining of a pale yellow oil using 1-Boc-3-hydroxypyrrolidine, the first reaction solvent, the organic base, and the substituted sulfonyl chloride comprises:

the mass volume ratio of the 1-Boc-3-hydroxypyrrolidine to the first reaction solvent is 1g: (3-20) mL;

the equivalent ratio of the 1-Boc-3-hydroxypyrrolidine to the organic base is less than or equal to 1/2;

the equivalent ratio of the 1-Boc-3-hydroxypyrrolidine to the substituted sulfonyl chloride is 1 (1-4).

5. The method of synthesizing 1-Boc-3-chlorosulfonylpyrrolidine according to claim 1, wherein the dissolving the pale yellow oil in the second reaction solvent and reacting with the thioacetate to obtain a yellow oil comprises:

dissolving pale yellow oily matter in a second reaction solvent;

adding thioacetate into the second mixed solution, heating the second mixed solution to 40-100 ℃, and standing for reaction for more than 1 h;

diluting the second mixed solution with deionized water, sequentially extracting with methyl tertiary butyl ether, washing the diluted second mixed solution with sodium chloride aqueous solution, drying, concentrating, and processing the second mixed solution to obtain yellow oily matter.

6. The method of synthesizing 4-Boc-3-chlorosulfonylpyrrolidine according to claim 5, wherein the dissolving the pale yellow oil in the second reaction solvent and reacting with the thioacetate to obtain a yellow oil comprises:

the thioacetate is selected from one of potassium thioacetate, sodium thioacetate and lithium thioacetate;

the second reaction solvent is selected from one of N, N-dimethylformamide, N-dimethylacetamide and N-methylpyrrolidone.

7. The method of synthesizing 4-Boc-3-chlorosulfonylpyrrolidine according to claim 5, wherein the dissolving the pale yellow oil in the second reaction solvent and reacting with the thioacetate to obtain a yellow oil comprises:

the equivalent ratio of the second reaction solvent to the pale yellow oily matter is more than or equal to 1;

the mass volume ratio of the pale yellow oily matter to the second reaction solvent is 1g:5mL.

8. The method for synthesizing 1-Boc-3-chlorosulfonylpyrrolidine according to claim 1, wherein the dissolving the yellow oil in the third reaction solvent and introducing a displacement gas to react, the obtaining a light brown oil comprises:

taking light brown oily matter, dissolving the light brown oily matter in a third reaction solvent, and cooling the third mixed solution to-20 ℃;

introducing replacement gas into the third mixed solution, keeping the temperature of the third mixed solution below 0 ℃, and standing for more than 1h for reaction;

and diluting the third mixed solution by using the first deionized water, washing the third mixed solution by using a sodium chloride aqueous solution and the second deionized water in sequence, and concentrating the third mixed solution to obtain light brown oily matter.

9. The method for synthesizing 1-Boc-3-chlorosulfonylpyrrolidine according to claim 8, wherein the dissolving the yellow oil in the third reaction solvent and introducing a displacement gas to react, the obtaining a light brown oil comprises:

the replacement gas is chlorine or sulfonyl chloride;

the third reaction solvent is selected from one of dichloromethane solvent, ethyl acetate, ethanol, methanol and tetrahydrofuran.

10. The method for synthesizing 1-Boc-3-chlorosulfonylpyrrolidine according to claim 8, wherein the dissolving the yellow oil in the third reaction solvent and introducing a displacement gas to react, the obtaining a light brown oil comprises:

the mass volume ratio of the yellow oily matter to the third reaction solvent is 1g:10mL;

the volume ratio of the third reaction solvent to the first deionized water to the sodium chloride aqueous solution to the second deionized water is 1:1:1:1, a step of;

and the equivalent ratio of the replacement gas to the yellow oily matter is more than or equal to 3.