阅读说明：本技术 一种5-(2-氟苯基)-1h-吡咯-3-甲醛的制备方法 (Preparation method of 5- (2-fluorophenyl) -1H-pyrrole-3-formaldehyde ) 是由 姚红 罗瑾 郑杰 杨玉平 张应军 谭艳红 于 2021-08-16 设计创作，主要内容包括：本发明属于医药化工技术领域,具体涉及一种5-(2-氟苯基)-1H-吡咯-3-甲醛的制备方法。本发明提供的5-(2-氟苯基)-1H-吡咯-3-甲醛的制备方法,包括以下步骤：将2-[2-(2-氟苯基)-2-氧代乙基]丙二腈、雷尼镍、溶剂、酸性pH值调节剂和还原剂混合,在酸性条件下进行一步反应,得到5-(2-氟苯基)-1H-吡咯-3-甲醛。按照本发明提供的制备方法能够以2-[2-(2-氟苯基)-2-氧代乙基]丙二腈为主要反应物以雷尼镍为催化剂一步合成5-(2-氟苯基)-1H-吡咯-3-甲醛,操作简单反应条件温和,减少了反应步骤。(The invention belongs to the technical field of pharmaceutical chemicals, and particularly relates to a preparation method of 5- (2-fluorophenyl) -1H-pyrrole-3-formaldehyde. The preparation method of the 5- (2-fluorophenyl) -1H-pyrrole-3-formaldehyde provided by the invention comprises the following steps: mixing 2- [2- (2-fluorophenyl) -2-oxoethyl ] malononitrile, raney nickel, a solvent, an acidic pH value regulator and a reducing agent, and carrying out one-step reaction under an acidic condition to obtain the 5- (2-fluorophenyl) -1H-pyrrole-3-formaldehyde. According to the preparation method provided by the invention, the 5- (2-fluorophenyl) -1H-pyrrole-3-formaldehyde can be synthesized in one step by taking 2- [2- (2-fluorophenyl) -2-oxoethyl ] malononitrile as a main reactant and Raney nickel as a catalyst, the operation is simple, the reaction condition is mild, and the reaction steps are reduced.)

1. A preparation method of 5- (2-fluorophenyl) -1H-pyrrole-3-formaldehyde comprises the following steps:

mixing 2- [2- (2-fluorophenyl) -2-oxoethyl ] malononitrile, raney nickel, a solvent, an acidic pH value regulator and a reducing agent, and carrying out one-step reaction under an acidic condition to obtain the 5- (2-fluorophenyl) -1H-pyrrole-3-formaldehyde.

2. The method of claim 1, wherein the mixing comprises the steps of:

firstly mixing 2- [2- (2-fluorophenyl) -2-oxoethyl ] malononitrile, a solvent and an acidic pH value regulator to obtain a first reaction liquid;

dispersing Raney nickel in the first reaction liquid to obtain a second reaction liquid;

adding a reducing agent to the second reaction solution.

3. The preparation method according to claim 1, wherein the temperature of the one-step reaction is 20-80 ℃ and the time is 2.8-3.2 h.

4. The preparation method according to claim 1, wherein the mass ratio of the 2- [2- (2-fluorophenyl) -2-oxoethyl ] malononitrile to the raney nickel is 1: 0.2-0.5.

5. The production method according to claim 1, wherein the reducing agent includes hydrogen gas or sodium hypophosphite.

6. The method according to claim 1 or 5, wherein the molar ratio of the reducing agent to 2- [2- (2-fluorophenyl) -2-oxoethyl ] malononitrile is 1-10: 1.

7. The production method according to claim 1 or 2, wherein the acidic pH adjuster comprises one or more of acetic acid, formic acid, phosphoric acid, and benzenesulfonic acid;

the pH value under the acidic condition is 5.5-6.5.

8. The method of claim 1, wherein the solvent comprises one or more of an alcohol, water, and tetrahydrofuran.

9. The preparation method according to claim 1 or 8, wherein the mass ratio of the 2- [2- (2-fluorophenyl) -2-oxoethyl ] malononitrile to the solvent is 1: 2-10.

10. The preparation method according to claim 1, further comprising, after the one-step reaction:

filtering the product after reaction, and taking the filtrate;

carrying out primary purification on the filtrate to obtain a crude product;

and refining the crude product to obtain a high-purity product.

Technical Field

The invention belongs to the technical field of pharmaceutical chemicals, and particularly relates to a preparation method of 5- (2-fluorophenyl) -1H-pyrrole-3-formaldehyde.

Background

Vonoprazan fumarate (TAK-438, Vonoprazan fumarate), chemically known as 1- (5- (2-fluorophenyl) -1- (pyridin-3-ylsulfonyl) -1H-pyrrol-3-yl) -N-methyl methylamine fumarate, is a novel oral gastric acid resistant drug developed in cooperation with tsukamur medicaments in wutian pharmacy, and is used for erosive esophagitis, gastric ulcer and duodenal ulcer. Marketed in japan on 26.12.2014 under the trade name Takecab for the treatment of acid-related diseases. Vonoprazan fumarate belongs to potassium ion (K)⁺) Competitive acid blocker (P-CAB), a reversible proton pump agent, is secreted in gastric parietal cells by K⁺And H⁺-K⁺The product has strong and durable gastric acid secretion effect, and compared with the traditional irreversible proton pump agents (such as omeprazole, esomeprazole and the like), the vonoprazan fumarate (Takecab) has the following advantages: the effect is quick, and the acid inhibition effect can be achieved by the administration on the 1 st day; ② the oral administration is not affected by gastric acid, and does not need to be made into an enteric administration form; and thirdly, the acid breakthrough phenomenon at night is improved to a certain extent.

5- (2-fluorophenyl) -1H-pyrrole-3-carbaldehyde is an important intermediate for preparing Vonoprazan fumarate, and Japanese Wutian pharmaceutical company, in Chinese application CN102421753A, discloses a synthetic route of 5- (2-fluorophenyl) -1H-pyrrole-3-carbaldehyde:

the route is long and uses expensive palladium as a catalyst, and 2-fluoro acetophenone is used as an initial material, and 5- (2-fluorophenyl) -1H-pyrrole-3-formaldehyde is obtained by bromination, malononitrile condensation, cyclization, dechlorination and cyano reduction. The document Discovery of a novel pyrrole derivative1- [5- (2-fluorophenyl) -1- (pyridine-3-ylsulfonyl) -1H-pyrrrol-3-yl ] -N-methylethane amine fumarate (TAK-438) as a pore-reactive acid blocker (P-CAB) (Yasuyoshi Arikawa Et. al., Journal of Medicinal Chemistry,2012,55, 4446-:

this route is similar to the route of patent CN102421753A applied by martian pharmaceutical company in japan in china, which is long and uses a relatively expensive palladium catalyst. Patent CN106243008A applied by shandong jincheng medicine gmbh discloses a synthetic route of 5- (2-fluorophenyl) -1H-pyrrole-3-formaldehyde:

the route is also long, which is not beneficial to industrialization.

The existing process route for preparing 5- (2-fluorophenyl) -1H-pyrrole-3-formaldehyde is long and is not beneficial to industrial production.

Disclosure of Invention

In view of the above, the invention provides a preparation method of 5- (2-fluorophenyl) -1H-pyrrole-3-formaldehyde, and the preparation method provided by the invention can synthesize a target product in one step, reduces reaction steps, is simple to operate and is beneficial to industrial production.

In order to solve the technical problem, the invention provides a preparation method of 5- (2-fluorophenyl) -1H-pyrrole-3-formaldehyde, which comprises the following steps:

mixing 2- [2- (2-fluorophenyl) -2-oxoethyl ] malononitrile, raney nickel, a solvent, an acidic pH value regulator and a reducing agent, and carrying out one-step reaction under an acidic condition to obtain the 5- (2-fluorophenyl) -1H-pyrrole-3-formaldehyde.

Preferably, the mixing comprises the steps of:

firstly mixing 2- [2- (2-fluorophenyl) -2-oxoethyl ] malononitrile, a solvent and an acidic pH value regulator to obtain a first reaction liquid;

dispersing Raney nickel in the first reaction liquid to obtain a second reaction liquid;

adding a reducing agent to the second reaction solution.

Preferably, the temperature of the one-step reaction is 20-80 ℃, and the time is 2.8-3.2 h.

Preferably, the mass ratio of the 2- [2- (2-fluorophenyl) -2-oxoethyl ] malononitrile to the raney nickel is 1: 0.2-0.5.

Preferably, the reducing agent comprises hydrogen or sodium hypophosphite.

Preferably, the molar ratio of the reducing agent to the 2- [2- (2-fluorophenyl) -2-oxoethyl ] malononitrile is 1-10: 1.

Preferably, the acidic pH adjuster comprises one or more of acetic acid, formic acid, phosphoric acid, and benzenesulfonic acid;

the pH value under the acidic condition is 5.5-6.5.

Preferably, the solvent comprises one or more of an alcohol, water and tetrahydrofuran.

Preferably, the mass ratio of the 2- [2- (2-fluorophenyl) -2-oxoethyl ] malononitrile to the solvent is 1: 2-10.

Preferably, the one-step reaction further comprises:

filtering the product after reaction, and taking the filtrate;

carrying out primary purification on the filtrate to obtain a crude product;

and refining the crude product to obtain a high-purity product.

The invention provides a preparation method of 5- (2-fluorophenyl) -1H-pyrrole-3-formaldehyde, which comprises the following steps: mixing 2- [2- (2-fluorophenyl) -2-oxoethyl ] malononitrile, raney nickel, a solvent, an acidic pH value regulator and a reducing agent, and carrying out one-step reaction under an acidic condition to obtain the 5- (2-fluorophenyl) -1H-pyrrole-3-formaldehyde. According to the preparation method provided by the invention, 2- [2- (2-fluorophenyl) -2-oxoethyl ] malononitrile is used as a main reactant, Raney's nickel is used as a catalyst, and 5- (2-fluorophenyl) -1H-pyrrole-3-formaldehyde can be synthesized in one step, so that the operation is simple, and the reaction steps are reduced; meanwhile, strong corrosive reagents such as bromine, hydrogen chloride and the like are avoided being adopted in the synthetic route in the prior art, and expensive palladium is also avoided being used as a catalyst.

Drawings

FIG. 1 is a liquid chromatogram of the product prepared in example 1;

FIG. 2 is a hydrogen spectrum of the product prepared in example 1;

FIG. 3 is a mass spectrum of the product prepared in example 1;

FIG. 4 is a liquid chromatogram of the product prepared in comparative example 1;

FIG. 5 is a mass spectrum of the product prepared in comparative example 1.

Detailed Description

The invention provides a preparation method of 5- (2-fluorophenyl) -1H-pyrrole-3-formaldehyde, which comprises the following steps:

mixing 2- [2- (2-fluorophenyl) -2-oxoethyl ] malononitrile, raney nickel, a solvent, an acidic pH value regulator and a reducing agent, and carrying out one-step reaction under an acidic condition to obtain the 5- (2-fluorophenyl) -1H-pyrrole-3-formaldehyde.

The 2- [2- (2-fluorophenyl) -2-oxoethyl ] malononitrile used in the present invention is preferably a conventional commercially available product, more preferably a product obtained from Shandongxuan medical science and technology Co. In the present invention, the mass ratio of the 2- [2- (2-fluorophenyl) -2-oxoethyl ] malononitrile to the raney nickel is preferably 1:0.2 to 0.5, and more preferably 1:0.35 to 0.49.

In the present invention, the solvent preferably includes one or more of alcohol, water and tetrahydrofuran, and more preferably a mixture of alcohol and water or a mixture of tetrahydrofuran and water. In the present invention, the alcohol preferably includes methanol, ethanol, t-butanol or isopropanol, and more preferably methanol or ethanol. In the present invention, when the solvent includes two or more of the above specific substances, the ratio of the specific substances in the present invention is not particularly limited, and any ratio may be used. In the embodiment of the invention, the solvent is a mixture of tetrahydrofuran and water in a volume ratio of 13:5, or a mixture of ethanol and water in a volume ratio of 8: 3. In the invention, the mass ratio of the 2- [2- (2-fluorophenyl) -2-oxoethyl ] malononitrile to the solvent is preferably 1: 2-10, more preferably 1: 4-8, and still more preferably 1: 4.9-5.5.

In the present invention, the acidic pH adjustor preferably comprises one or more of acetic acid, formic acid, phosphoric acid and benzenesulfonic acid, more preferably acetic acid. In the present invention, when the acidic pH adjustor includes two or more of the above-mentioned specific substances, the ratio of the specific substances in the present invention is not particularly limited, and any ratio may be used. In the present invention, the pH value of the acidic condition is preferably 5.5 to 6.5, and more preferably 6. The amount of the acidic pH regulator used in the present invention is not particularly limited as long as the desired pH can be achieved.

In the present invention, the reducing agent preferably comprises hydrogen gas or sodium hypophosphite, more preferably sodium hypophosphite. In the invention, the molar ratio of the reducing agent to the 2- [2- (2-fluorophenyl) -2-oxoethyl ] malononitrile is preferably 1-10: 1, more preferably 2-6: 1, and still more preferably 3-4: 1.

In the present invention, the mixing preferably comprises the steps of:

firstly mixing 2- [2- (2-fluorophenyl) -2-oxoethyl ] malononitrile, a solvent and an acidic pH value regulator to obtain a first reaction liquid;

dispersing Raney nickel in the first reaction liquid to obtain a second reaction liquid;

adding a reducing agent to the second reaction solution.

The method comprises the steps of mixing 2- [2- (2-fluorophenyl) -2-oxoethyl ] malononitrile, a solvent and an acidic pH value regulator for the first time to obtain a first reaction liquid. In the invention, the temperature of the first mixing is preferably 20-25 ℃, and more preferably 22-24 ℃. In the present invention, the first mixing is preferably performed under stirring, and the stirring time in the present invention is not particularly limited as long as the first mixing can be uniformly mixed.

After the first reaction liquid is obtained, Raney nickel is dispersed in the first reaction liquid to obtain a second reaction liquid. The dispersion is not particularly limited in the present invention as long as it can be uniformly mixed.

After the second reaction solution is obtained, the reducing agent is added into the second reaction solution. In the invention, when the reducing agent is hydrogen, the hydrogen is preferably introduced into the second reaction solution, and the pressure of the introduced hydrogen is preferably 0.08-0.12 MPa, and more preferably 0.1 MPa. When sodium hypophosphite is selected as the reducing agent, preferably, the sodium hypophosphite is dissolved in water to prepare a sodium hypophosphite solution, and then the sodium hypophosphite solution is dripped into the second reaction liquid. In the invention, the concentration of the sodium hypophosphite solution is preferably 0.7-0.9 g/mL, and more preferably 0.76-0.84 g/mL. In the invention, the dripping speed is preferably 10-15 drops/min, and more preferably 12-14 drops/min. The dropping time is not particularly limited, and the dropping can be completed. In the examples of the present invention, the dropping time was 30 min.

The invention can control the reaction rate by limiting the flow of the introduced hydrogen and the dropping rate of the added sodium hypophosphite solution, thereby effectively controlling the reaction temperature, preventing the temperature from rising and reducing the generation of impurities.

In the present invention, the pH of the reaction solution is preferably 5.5 to 6.5, and more preferably 6. The invention limits the pH value of the reaction liquid in the range, can ensure normal one-step reaction, can avoid catalyst deactivation, can not normally perform one-step reaction when the pH value of the reaction liquid is too high, and can easily deactivate the catalyst when the pH value is too low.

In the invention, the temperature of the one-step reaction is preferably 20-80 ℃, more preferably 30-50 ℃, and further preferably 35-40 ℃; the time of the one-step reaction is preferably 2.8-3.2 h, and more preferably 3 h.

In the present invention, the reaction equation of the one-step reaction is shown in formula 1:

in the present invention, the one-step reaction preferably further comprises:

filtering the product after reaction, and taking the filtrate;

carrying out primary purification on the filtrate to obtain a crude product;

and refining the crude product to obtain a high-purity product.

The invention filters the product after reaction and takes the filtrate. The filter residue is preferably washed by tetrahydrofuran in the filtering process. In the present invention, the number of washing is preferably 1 to 3, and more preferably 2. The filtration is not particularly limited in the present invention and may be performed in a manner conventional in the art. In the present invention, the filtration enables the separation and recovery of raney nickel.

After the filtrate is obtained, the filtrate is primarily purified to obtain a crude product. In the present invention, the primary purification preferably comprises the steps of:

separating the filtrate, and distilling the upper organic layer;

dissolving the solid obtained by distillation in a mixed solution of ethyl acetate and a hydrochloric acid aqueous solution, adjusting the pH value to 3.8-4.2, then carrying out liquid separation, taking an upper organic phase, and extracting a water phase by using ethyl acetate to obtain a second organic phase;

and (4) combining the organic phase and the second organic phase, and carrying out reduced pressure distillation to obtain a crude product.

In the invention, the filtrate is subjected to liquid separation, and an upper organic layer is taken for distillation. The present invention is not particularly limited to the liquid separation, and may be carried out in a manner conventional in the art. In the invention, the distillation is preferably reduced pressure distillation, and the temperature of the reduced pressure distillation is preferably 58-62 ℃, and more preferably 60 ℃. In the present invention, the time for the reduced pressure distillation is not particularly limited as long as the solvent can be removed.

The method comprises the steps of dissolving a solid obtained by distillation in a mixed solution of ethyl acetate and a hydrochloric acid aqueous solution, adjusting the pH value to 3.8-4.2, separating the solution, taking an upper organic phase, and extracting an aqueous phase by using ethyl acetate to obtain a second organic phase. In the invention, the concentration of the hydrochloric acid aqueous solution is preferably 0.8-1.2 mol/L, and more preferably 1 mol/L. In the present invention, the volume ratio of the ethyl acetate to the hydrochloric acid aqueous solution in the mixed solution is preferably 0.8 to 1.2:1, and more preferably 1: 1. In the present invention, the mass ratio of the solid obtained by the distillation to the ethyl acetate in the mixed solution is preferably 1: 3-10, more preferably 1:4 to 6. The method for adjusting the pH value to 4 is not particularly limited, so long as the required pH value can be achieved. In the embodiment of the invention, hydrochloric acid solution with the molar concentration of 6mol/L is adopted for adjustment. The present invention is not particularly limited to the liquid separation, and may be carried out in a manner conventional in the art. The extraction is not particularly limited in the present invention and may be performed in a manner conventional in the art.

The organic phase and the second organic phase are combined and subjected to reduced pressure distillation to obtain a crude product. In the invention, the temperature of the reduced pressure distillation is preferably 58-62 ℃, and more preferably 60 ℃. In the present invention, the time for the reduced pressure distillation is not particularly limited as long as the solvent can be removed.

After the crude product is obtained, the invention refines the crude product to obtain a high-purity product. In the present invention, the refining preferably comprises the steps of:

dissolving the crude product in acetonitrile to obtain an acetonitrile solution of the crude product;

and mixing the acetonitrile solution of the crude product with water, and then sequentially carrying out cooling crystallization and filtration to obtain a high-purity product.

The crude product is dissolved in acetonitrile to obtain an acetonitrile solution of the crude product. In the invention, the dissolving temperature is preferably 53-57 ℃, and more preferably 55 ℃. In the invention, the mass ratio of the crude product to the acetonitrile is preferably 34.3-68-72, and more preferably 34.3: 70.

After the acetonitrile solution of the crude product is obtained, the acetonitrile solution of the crude product and water are mixed, then cooling crystallization and filtration are sequentially carried out, and a filter cake obtained by filtration is leached to obtain a high-purity product. In the invention, the mass ratio of the water to the acetonitrile is preferably 1.8-2.2: 1, and more preferably 2: 1. In the invention, the temperature reduction crystallization is preferably reduced to 23-27 ℃, and more preferably to 25 ℃. In the invention, the crystallization time of the temperature-reducing crystallization is preferably 1.8-2.2 h, and more preferably 2 h. The filtration is not particularly limited in the present invention and may be performed in a manner conventional in the art. In the present invention, the solvent for rinsing is preferably acetonitrile water-soluble. In the present invention, the mass concentration of the acetonitrile aqueous solution is preferably 18 to 22%, and more preferably 20%. In the present invention, after the rinsing, the rinsing further preferably includes: and drying the washing liquid obtained by leaching. In the present invention, the drying is preferably vacuum drying, and the vacuum degree of the vacuum drying is preferably-0.12 to-0.08 MPa, and more preferably-0.1 MPa; the temperature of the vacuum drying is preferably 53-57 ℃, and more preferably 55 ℃; the vacuum drying time is preferably 14-18 h, and more preferably 16 h. In the present invention, the highly pure product is yellow.

In order to further illustrate the present invention, the following embodiments are described in detail, but they should not be construed as limiting the scope of the present invention.

Example 1

36.5g of 2- [2- (2-fluorophenyl) -2-oxoethyl ] malononitrile, which is purchased from Shandongxuan medical science and technology Co., Ltd., 130mL of tetrahydrofuran, 105mL of acetic acid and 50mL of water are stirred and mixed at 25 ℃ to obtain a first reaction solution;

dispersing 18g of Raney nickel in the first reaction liquid to obtain a second reaction liquid;

dripping 120mL of sodium hypophosphite aqueous solution with the mass concentration of 0.76g/mL into the second reaction liquid according to the dripping speed of 12 drops/min, and finishing the dripping within 30 min; reacting for 3 hours in one step at 40 ℃;

filtering a product after reaction, washing filter residues twice by using 50mL of tetrahydrofuran respectively, separating the filtrate obtained by filtering, and carrying out reduced pressure distillation on an upper organic layer at 60 ℃; dissolving the solid obtained by distillation in a mixed solution of 200mL of ethyl acetate and 200mL of hydrochloric acid aqueous solution with the molar concentration of 1mol/L, adjusting the pH value to 4 by using 6mol/L hydrochloric acid aqueous solution, separating the solution, and taking an organic phase; extracting the water phase by using 100mL of ethyl acetate to obtain a second organic phase, combining the organic phase and the second organic phase, and then carrying out reduced pressure distillation at 60 ℃ to obtain 34.3g of a crude product;

dissolving 34.3g of the crude product in 70g of acetonitrile at 55 ℃, mixing with 140g of water, cooling to 25 ℃, crystallizing for 2h, filtering, leaching a filter cake with 50mL of acetonitrile aqueous solution with the mass concentration of 20%, and drying the obtained leaching solution in vacuum for 16h under the conditions of the temperature of 55 ℃ and the vacuum degree of-0.1 MPa to obtain 28.5g of a yellow solid; the yellow solid was 5- (2-fluorophenyl) -1H-pyrrole-3-carbaldehyde with a yield of 85.0% and a purity of 99%.

Example 2

20.2g of 2- [2- (2-fluorophenyl) -2-oxoethyl ] malononitrile, which is purchased from Shandongxuan medical science and technology Co., Ltd., 80mL of ethanol, 60mL of acetic acid and 30mL of water are stirred and mixed at 25 ℃ to obtain a first reaction solution;

dispersing 10g of Raney nickel in the first reaction liquid to obtain a second reaction liquid;

dropwise adding 700mL of sodium hypophosphite aqueous solution with the mass concentration of 0.84g/mL into the second reaction liquid according to the dropwise adding speed of 13 drops/min, and completing dropwise adding within 30 min; reacting for 3 hours in one step at 38 ℃;

filtering a product after reaction, washing filter residues twice by using 50mL of tetrahydrofuran respectively, separating the filtrate obtained by filtering, and carrying out reduced pressure distillation on an upper organic layer at 60 ℃; dissolving the solid obtained by distillation in a mixed solution of 200mL of ethyl acetate and 200mL of hydrochloric acid aqueous solution with the molar concentration of 1mol/L, adjusting the pH value to 4 by using 6mol/L hydrochloric acid aqueous solution, separating the solution, and taking an organic phase; extracting the water phase by using 100mL of ethyl acetate to obtain a second organic phase, combining the organic phase and the second organic phase, and then carrying out reduced pressure distillation at 60 ℃ to obtain 18.1g of a crude product;

dissolving 18.1g of crude product in 40g of acetonitrile at 55 ℃, mixing with 80g of water, cooling to 25 ℃, crystallizing for 2h, filtering, leaching a filter cake with 50mL of acetonitrile aqueous solution with the mass concentration of 20%, and drying the obtained leaching solution in vacuum for 16h under the conditions of the temperature of 55 ℃ and the vacuum degree of-0.1 MPa to obtain 15.7g of yellow solid; the yellow solid was 5- (2-fluorophenyl) -1H-pyrrole-3-carbaldehyde with a yield of 83.2% and a purity of 99%.

Example 3

5- (2-fluorophenyl) -1H-pyrrole-3-carbaldehyde was prepared by the method of example 1, except that the reducing agent was replaced with hydrogen gas from sodium hypophosphite, and the pressure of the hydrogen gas introduced into the second reaction liquid was 0.1 MPa; the 5- (2-fluorophenyl) -1H-pyrrole-3-carbaldehyde was prepared in a yield of 75% and a purity of 98%.

Comparative example 1

An experiment was conducted in accordance with the procedure of example 3 except that the catalyst was replaced with 18g of Raney nickel and 3.6g of 5% palladium on carbon.

Performing liquid chromatography detection, hydrogen spectrum detection and mass spectrum detection on the product of example 1 to obtain figures 1-3, wherein figure 1 is a liquid chromatogram, figure 2 is a hydrogen spectrum, and figure 3 is a mass spectrum. The purity of the product was determined from FIG. 1 and, in combination with FIGS. 2 and 3, the product was 5- (2-fluorophenyl) -1H-pyrrole-3-carbaldehyde.

And (3) carrying out liquid chromatography detection and mass spectrometry detection on the product of the comparative example 1 to obtain a liquid chromatogram and a mass spectrum, wherein the liquid chromatogram is shown in fig. 4, and the mass spectrum is shown in fig. 5. In combination with FIG. 4 and FIG. 5, it can be determined that the product formed in comparative example 1 is not 5- (2-fluorophenyl) -1H-pyrrole-3-carbaldehyde, i.e., that the comparative example does not form 5- (2-fluorophenyl) -1H-pyrrole-3-carbaldehyde.

Although the present invention has been described in detail with reference to the above embodiments, it is only a part of the embodiments of the present invention, not all of the embodiments, and other embodiments can be obtained without inventive step according to the embodiments, and the embodiments are within the scope of the present invention.