CN112920233A - Synthetic method of emamectin benzoate with improved processability - Google Patents
Synthetic method of emamectin benzoate with improved processability Download PDFInfo
- Publication number
- CN112920233A CN112920233A CN202110208347.5A CN202110208347A CN112920233A CN 112920233 A CN112920233 A CN 112920233A CN 202110208347 A CN202110208347 A CN 202110208347A CN 112920233 A CN112920233 A CN 112920233A
- Authority
- CN
- China
- Prior art keywords
- emamectin benzoate
- reaction
- carrying
- improved processability
- catalyst
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- C07H17/08—Hetero rings containing eight or more ring members, e.g. erythromycins
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a method for synthesizing emamectin benzoate with improved processability, which takes avermectin B1a as a starting material and obtains the emamectin benzoate by four reaction processes of oxidation, ammoniation, reduction and salification in sequence. The technical scheme adopted by the invention is convenient and fast to synthesize and operate, simplifies the process steps compared with the traditional route, reduces the production cost, and obtains the emamectin benzoate pure product with the yield of more than 70% and the purity of more than 95%.
Description
Technical Field
The invention relates to the technical field of drug synthesis, in particular to a synthetic method of emamectin benzoate with improved processability.
Background
The emamectin benzoate is a novel high-efficiency semi-synthetic antibiotic pesticide synthesized from a fermentation product, namely, abamectin B1, and has the characteristics of super-high efficiency, low toxicity (the preparation is nearly nontoxic), low residue, no public nuisance and other biological pesticides. Is widely used for preventing and controlling various pests on crops such as vegetables, fruit trees, cotton and the like. The existing method for preparing emamectin benzoate mainly takes avermectin as a raw material, and hydroxyl on the 4' -position of the avermectin is transformed into methylamino. The crude emamectin benzoate is obtained through hydroxyl protection, oxidation, ammoniation, hydrogenation reduction, deprotection reaction, salifying reaction and the like in the main synthesis steps, the process is complex, and the production cost of the emamectin benzoate is high and the economic benefit is low due to the fact that the steps are multiple, the related consumption and three wastes are multiple. Therefore, it is necessary to optimize the route to reduce the components, the three wastes and improve the industrial value of the emamectin benzoate.
Disclosure of Invention
In view of the above, the present invention provides a synthetic method of emamectin benzoate, which improves the processability thereof. The technical scheme of the invention is as follows:
a synthetic method of emamectin benzoate capable of improving the processability of the emamectin benzoate takes avermectin B1a as a starting material and obtains the emamectin benzoate through four reaction processes of oxidation, ammoniation, reduction and salification in sequence.
Further, the preparation method specifically comprises the following steps:
(a) dissolving abamectin B1a in a first solvent, carrying out oxidation reaction with di-tert-butyl peroxide under the action of a catalyst, and then carrying out post-treatment to obtain an intermediate I;
(b) dissolving the intermediate I and heptamethyldisilazane in a second solvent, carrying out amination reaction under the action of an alkaline catalyst, and then carrying out aftertreatment to obtain an intermediate II;
(c) carrying out reduction reaction on the intermediate II under the action of a catalyst, and then carrying out aftertreatment to obtain a 4' -methylamino abamectin solution;
(d) and carrying out salt forming reaction on the 4' -emamectin benzoate solution and benzoic acid to obtain a crude emamectin benzoate product, and then purifying to obtain a pure emamectin benzoate product.
The source of abamectin B1a in the present invention is not particularly limited, and it may be generally commercially available or prepared according to a method known to those skilled in the art.
In some embodiments of the present invention, the solvent in step (a) is dimethylformamide or toluene.
Preferably, the control parameters of the oxidation reaction in the step (a) are as follows: the catalyst is silver carbonate and dilute hydrochloric acid with volume concentration of 5%, the addition amount of the silver carbonate is 2-4% of the mass of the abamectin B1a, the reaction temperature is below 5 ℃, and the reaction time is 20-30 min.
In some embodiments of the present invention, the post-treatment process in step (a) comprises: sequentially adding a sodium bicarbonate solution with the mass concentration of 10-15% and a sodium sulfite solution with the mass concentration of 30-35% into an oxidation reaction system, and uniformly mixing; after filtration, the filtrate was concentrated to dryness and dried to give intermediate I.
Preferably, in the present invention, the solvent two in the step (b) is toluene.
In some embodiments of the invention, the control parameters for the amination reaction in step (b) are: the alkaline catalyst is one of sodium tert-butoxide, sodium methoxide and sodium ethoxide, the addition amount of the alkaline catalyst is 0.5-0.8 percent of the mass of the abamectin B1a, the reaction temperature is 25-35 ℃, and the reaction time is 30 min-1 h.
In some embodiments of the present invention, the post-processing in step (b) comprises: and filtering after the ammoniation reaction is finished, and concentrating the filtrate to be dry to obtain an intermediate II.
In some embodiments of the present invention, the control parameters of the reduction reaction in step (c) are: the catalyst is sodium borohydride, the adding amount of the catalyst is 5% of the mass of the abamectin B1a, the solvent is toluene, the reaction temperature is 40-45 ℃, and the reaction time is 15-30 min.
In some embodiments of the present invention, the post-processing in step (c) comprises: terminating the reaction by using an acetic acid solution with the volume concentration of 10%, adding a sodium carbonate solution with the mass concentration of 10% to adjust the pH value to 7-8, layering, extracting a water phase by using toluene, combining organic phases, and concentrating until the volume of the water phase is 1/3-1/4.
In some embodiments of the invention, the purification process in step (d) comprises: dissolving the crude emamectin benzoate by using a polar solvent, and then sequentially carrying out fine filtration and membrane filtration; adding purified water into the filtrate, concentrating until solid is separated out, cooling for crystallization, filtering and drying.
In the present invention, preferably, the polar solvent is at least one of methanol, ethanol and acetone.
Preferably, the membrane filtration is performed by using a ceramic membrane with the pore diameter of less than 0.02 mu m.
The filtration method of the present invention is not particularly limited, and may be a method known to those skilled in the art, such as suction filtration, pressure filtration, etc.
The technical scheme adopted by the invention is convenient and fast to synthesize, simplifies the process steps compared with the traditional route, reduces the production cost, and obtains the emamectin benzoate pure product with the purity of more than 95%.
Detailed Description
In the description of the present invention, it is to be noted that those whose specific conditions are not specified in the examples are carried out according to the conventional conditions or the conditions recommended by the manufacturers. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially. The following examples are only for the purpose of helping understanding the method of the present invention and the core idea thereof, and are not to be construed as limiting the present invention, it should be noted that those skilled in the art can make several improvements and modifications to the present invention without departing from the principle of the present invention, and these improvements and modifications also fall within the protection scope of the claims of the present invention.
The present invention will now be described in further detail with reference to specific examples, which are intended to be illustrative, but not limiting, of the invention.
Example 1
This example provides a method for synthesizing emamectin benzoate, which improves its processability, comprising the following steps:
(a) dissolving abamectin B1a 87.3.3 g (0.1mol) in 600mL of dimethylformamide, and carrying out oxidation reaction with di-tert-butyl peroxide under the action of a catalyst, wherein the specific control parameters are as follows: the catalyst is silver carbonate and dilute hydrochloric acid with volume concentration of 5%, the addition amount of the silver carbonate is 2.6g, the addition amount of the dilute hydrochloric acid with volume concentration of 5% is 50mL, the reaction temperature is-2 ℃, and the reaction time is 30 min. Then, sequentially adding 30mL of sodium bicarbonate solution with the mass concentration of 15% and 2mL of sodium sulfite solution with the mass concentration of 30% into an oxidation reaction system, and uniformly mixing; after filtration, the filtrate was concentrated to dryness and dried to give intermediate I.
(b) Dissolving the intermediate I and 21g (0.12mol) of heptamethyldisilazane in toluene, and carrying out amination reaction under the action of 0.6g of sodium tert-butoxide, wherein the specific control parameters are as follows: the reaction temperature is 28-30 ℃, and the reaction time is 40 min. Then filtered and the filtrate concentrated to dryness to give intermediate II.
(c) Carrying out reduction reaction on the intermediate II under the action of sodium borohydride, wherein the specific control parameters are as follows: adding 4.36g of sodium borohydride, taking toluene as a solvent, reacting at 40-42 ℃ for 20min, terminating the reaction with 10% acetic acid solution, adding 10% sodium carbonate solution to adjust the pH value to 7.8, layering, extracting the water phase with toluene, combining the organic phases, and concentrating until 1/3 is left in volume to obtain the 4' -emamectin benzoate solution.
(d) Adding 14.6g of benzoic acid into a 4' -emamectin benzoate solution, stirring for 2 hours to obtain a emamectin benzoate crude product, then concentrating to dryness, and then purifying to obtain an emamectin benzoate pure product, wherein the purification process comprises the following steps: dissolving the crude emamectin benzoate by 50mL of methanol, and then sequentially carrying out fine filtration and membrane filtration (a ceramic membrane with the aperture less than 0.02 mu m); 600mL of purified water is added into the filtrate, the mixture is concentrated until solid is separated out, the temperature is reduced to 5 ℃ for crystallization for 1h, and the mixture is filtered and dried to obtain 74.7g of emamectin benzoate, the yield is 74.1 percent, and the HPLC purity is 96.1 percent.
Example 2
This example provides a method for synthesizing emamectin benzoate, which improves its processability, comprising the following steps:
(a) dissolving 87.3g (0.1mol) of abamectin B1a 87.3 in 500mL of toluene, and carrying out oxidation reaction with di-tert-butyl peroxide under the action of a catalyst, wherein the specific control parameters are as follows: the catalyst is silver carbonate and dilute hydrochloric acid with volume concentration of 5%, the addition amount of the silver carbonate is 2.6g, the addition amount of the dilute hydrochloric acid with volume concentration of 5% is 50mL, the reaction temperature is-2 ℃, and the reaction time is 30 min. Then, sequentially adding 30mL of sodium bicarbonate solution with the mass concentration of 15% and 2mL of sodium sulfite solution with the mass concentration of 30% into an oxidation reaction system, and uniformly mixing; after filtration, the filtrate was concentrated to dryness and dried to give intermediate I.
(b) Dissolving the intermediate I and 21g (0.12mol) of heptamethyldisilazane in toluene, and carrying out amination reaction under the action of 0.5g of sodium methoxide, wherein the specific control parameters are as follows: the reaction temperature is 28-30 ℃, and the reaction time is 40 min. Then filtered and the filtrate concentrated to dryness to give intermediate II.
(c) Carrying out reduction reaction on the intermediate II under the action of sodium borohydride, wherein the specific control parameters are as follows: adding 4.36g of sodium borohydride, adding toluene as a solvent, reacting at 40-42 ℃ for 20min, terminating the reaction with 10 vol% acetic acid solution, adding 10 vol% sodium carbonate solution, adjusting the pH value to 7.5, layering, extracting the water phase with toluene, combining the organic phases, and concentrating until 1/3 is left in volume to obtain 4' -emamectin benzoate solution.
(d) Adding 14.6g of benzoic acid into a 4' -emamectin benzoate solution, stirring for 2 hours to obtain a emamectin benzoate crude product, then concentrating to dryness, and then purifying to obtain an emamectin benzoate pure product, wherein the purification process comprises the following steps: dissolving the crude emamectin benzoate by using 50mL of ethanol, and then sequentially carrying out fine filtration and membrane filtration (a ceramic membrane with the aperture being less than 0.02 mu m); 600mL of purified water is added into the filtrate, the mixture is concentrated until solid is separated out, the temperature is reduced to 5 ℃ for crystallization for 1h, and the mixture is filtered and dried to obtain 73.5g of emamectin benzoate, the yield is 72.9 percent, and the HPLC purity is 96.5 percent.
Example 3
This example provides a method for synthesizing emamectin benzoate, which improves its processability, comprising the following steps:
(a) dissolving 87.3g (0.1mol) of abamectin B1a 87.3 in 500mL of toluene, and carrying out oxidation reaction with di-tert-butyl peroxide under the action of a catalyst, wherein the specific control parameters are as follows: the catalyst is silver carbonate and dilute hydrochloric acid with volume concentration of 5%, the addition amount of the silver carbonate is 2.6g, the addition amount of the dilute hydrochloric acid with volume concentration of 5% is 50mL, the reaction temperature is-2 ℃, and the reaction time is 30 min. Then, sequentially adding 30mL of sodium bicarbonate solution with the mass concentration of 15% and 2mL of sodium sulfite solution with the mass concentration of 30% into an oxidation reaction system, and uniformly mixing; after filtration, the filtrate was concentrated to dryness and dried to give intermediate I.
(b) Dissolving the intermediate I and 21g (0.12mol) of heptamethyldisilazane in toluene, and carrying out amination reaction under the action of 0.5g of sodium ethoxide, wherein the specific control parameters are as follows: the reaction temperature is 28-30 ℃, and the reaction time is 40 min. Then filtered and the filtrate concentrated to dryness to give intermediate II.
(c) Carrying out reduction reaction on the intermediate II under the action of sodium borohydride, wherein the specific control parameters are as follows: adding 4.36g of sodium borohydride, adding toluene as a solvent, reacting at 40-42 ℃ for 20min, terminating the reaction with 10 vol% acetic acid solution, adding 10 vol% sodium carbonate solution, adjusting the pH value to 7.5, layering, extracting the water phase with toluene, combining the organic phases, and concentrating until 1/3 is left in volume to obtain 4' -emamectin benzoate solution.
(d) Adding 15g of benzoic acid into the 4' -emamectin benzoate solution, stirring for 2h to obtain a emamectin benzoate crude product, then concentrating to dryness, and then purifying to obtain an emamectin benzoate pure product, wherein the purification process comprises the following steps: dissolving the crude emamectin benzoate by using 50mL of acetone, and then sequentially carrying out fine filtration and membrane filtration (a ceramic membrane with the aperture being less than 0.02 mu m); 600mL of purified water is added into the filtrate, the mixture is concentrated until solid is separated out, the temperature is reduced to 5 ℃ for crystallization for 1h, and the mixture is filtered and dried to obtain 73.5g of emamectin benzoate, the yield is 72.9 percent, and the HPLC purity is 96.5 percent.
In conclusion, the technical scheme adopted by the invention is convenient and fast to synthesize and operate, compared with the traditional route, the process steps are simplified, the production cost is reduced, and the pure emamectin benzoate with the purity of more than 95% is obtained.
While the foregoing description shows and describes several preferred embodiments of the invention, it is to be understood, as noted above, that the invention is not limited to the forms disclosed herein, but is not to be construed as excluding other embodiments and is capable of use in various other combinations, modifications, and environments and is capable of changes within the scope of the inventive concept as expressed herein, commensurate with the above teachings, or the skill or knowledge of the relevant art. And that modifications and variations may be effected by those skilled in the art without departing from the spirit and scope of the invention as defined by the appended claims.
Claims (9)
1. A synthetic method of emamectin benzoate capable of improving the processability is characterized in that the emamectin benzoate is obtained by taking abamectin B1a as a starting raw material and sequentially carrying out four reaction processes of oxidation, ammoniation, reduction and salification.
2. The method for synthesizing emamectin benzoate with improved processability as claimed in claim 1, wherein the preparation method comprises the following steps:
(a) dissolving abamectin B1a in a first solvent, carrying out oxidation reaction with di-tert-butyl peroxide under the action of a catalyst, and then carrying out post-treatment to obtain an intermediate I;
(b) dissolving the intermediate I and heptamethyldisilazane in a second solvent, carrying out amination reaction under the action of an alkaline catalyst, and then carrying out aftertreatment to obtain an intermediate II;
(c) carrying out reduction reaction on the intermediate II under the action of a catalyst, and then carrying out aftertreatment to obtain a 4' -methylamino abamectin solution;
(d) and carrying out salt forming reaction on the 4' -emamectin benzoate solution and benzoic acid to obtain a crude emamectin benzoate product, and then purifying to obtain a pure emamectin benzoate product.
3. The method for synthesizing emamectin benzoate having improved processability as claimed in claim 2, wherein the solvent in step (a) is dimethylformamide or toluene.
4. The method for synthesizing emamectin benzoate with improved processability as claimed in claim 2, wherein the control parameters of the oxidation reaction in step (a) are as follows: the catalyst is silver carbonate and dilute hydrochloric acid with volume concentration of 5%, the addition amount of the silver carbonate is 2-4% of the mass of the abamectin B1a, the reaction temperature is below 5 ℃, and the reaction time is 20-30 min.
5. The method for synthesizing emamectin benzoate with improved processability as claimed in claim 2, wherein the post-treatment process in the step (a) comprises the following steps: sequentially adding a sodium bicarbonate solution with the mass concentration of 10-15% and a sodium sulfite solution with the mass concentration of 30-35% into an oxidation reaction system, and uniformly mixing; after filtration, the filtrate was concentrated to dryness and dried to give intermediate I.
6. The method for synthesizing emamectin benzoate with improved processability as claimed in claim 2, wherein the solvent II in step (b) is toluene.
7. A process for the synthesis of emamectin benzoate having improved processability as claimed in claim 2 wherein the control parameters for the amination reaction in step (b) are: the alkaline catalyst is one of sodium tert-butoxide, sodium methoxide and sodium ethoxide, the addition amount of the alkaline catalyst is 0.5-0.8 percent of the mass of the abamectin B1a, the reaction temperature is 25-35 ℃, and the reaction time is 30 min-1 h.
8. The method for synthesizing emamectin benzoate with improved processability as claimed in claim 2, wherein the parameters for controlling the reduction reaction in step (c) are as follows: the catalyst is sodium borohydride, the adding amount of the catalyst is 5% of the mass of the abamectin B1a, the solvent is toluene, the reaction temperature is 40-45 ℃, and the reaction time is 15-30 min.
9. The method for synthesizing emamectin benzoate with improved processability as claimed in claim 2, wherein the purification process in step (d) comprises: dissolving the crude emamectin benzoate by using a polar solvent, and then sequentially carrying out fine filtration and membrane filtration; adding purified water into the filtrate, concentrating until solid is separated out, cooling for crystallization, filtering and drying.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110208347.5A CN112920233A (en) | 2021-02-24 | 2021-02-24 | Synthetic method of emamectin benzoate with improved processability |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110208347.5A CN112920233A (en) | 2021-02-24 | 2021-02-24 | Synthetic method of emamectin benzoate with improved processability |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112920233A true CN112920233A (en) | 2021-06-08 |
Family
ID=76171641
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110208347.5A Pending CN112920233A (en) | 2021-02-24 | 2021-02-24 | Synthetic method of emamectin benzoate with improved processability |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112920233A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116444582A (en) * | 2023-04-18 | 2023-07-18 | 河北兴柏农业科技股份有限公司 | Emamectin benzoate purification process |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR059435A1 (en) * | 2006-11-08 | 2008-04-09 | Dow Agrosciences Llc | N-REPLACED SULFOXIMINES OF HETEROARIL RENT (REPLACED) AS INSECTICIDED |
| CN101817858A (en) * | 2010-04-15 | 2010-09-01 | 山东京博控股发展有限公司 | Method for synthesizing emamectin benzoate |
| CN104876990A (en) * | 2015-06-02 | 2015-09-02 | 宁夏泰瑞制药股份有限公司 | Method for purifying crude emamectin benzoate |
| US20160280660A1 (en) * | 2013-11-20 | 2016-09-29 | E. I. Du Pont De Nemours And Company | 1-aryl-3-alkylpyrazole insecticides |
| US20170355724A1 (en) * | 2014-10-22 | 2017-12-14 | Norbrook Laboratories Limited | Anthelminthic macrolide synthesis |
| CN108484702A (en) * | 2018-01-27 | 2018-09-04 | 湖北荆洪生物科技股份有限公司 | A kind of synthetic method of emamection benaoate |
| CN110563784A (en) * | 2019-09-20 | 2019-12-13 | 宁夏泰益欣生物科技有限公司 | Synthetic method of emamectin benzoate crude product |
-
2021
- 2021-02-24 CN CN202110208347.5A patent/CN112920233A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR059435A1 (en) * | 2006-11-08 | 2008-04-09 | Dow Agrosciences Llc | N-REPLACED SULFOXIMINES OF HETEROARIL RENT (REPLACED) AS INSECTICIDED |
| CN101817858A (en) * | 2010-04-15 | 2010-09-01 | 山东京博控股发展有限公司 | Method for synthesizing emamectin benzoate |
| US20160280660A1 (en) * | 2013-11-20 | 2016-09-29 | E. I. Du Pont De Nemours And Company | 1-aryl-3-alkylpyrazole insecticides |
| US20170355724A1 (en) * | 2014-10-22 | 2017-12-14 | Norbrook Laboratories Limited | Anthelminthic macrolide synthesis |
| CN104876990A (en) * | 2015-06-02 | 2015-09-02 | 宁夏泰瑞制药股份有限公司 | Method for purifying crude emamectin benzoate |
| CN108484702A (en) * | 2018-01-27 | 2018-09-04 | 湖北荆洪生物科技股份有限公司 | A kind of synthetic method of emamection benaoate |
| CN110563784A (en) * | 2019-09-20 | 2019-12-13 | 宁夏泰益欣生物科技有限公司 | Synthetic method of emamectin benzoate crude product |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116444582A (en) * | 2023-04-18 | 2023-07-18 | 河北兴柏农业科技股份有限公司 | Emamectin benzoate purification process |
| CN116444582B (en) * | 2023-04-18 | 2024-03-08 | 河北兴柏农业科技股份有限公司 | Emamectin benzoate purification process |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110305080A (en) | A kind of purification process of docetaxel | |
| CN112920233A (en) | Synthetic method of emamectin benzoate with improved processability | |
| KR100434991B1 (en) | Preparation method of N-methyl-N'-nitroguanidine | |
| CN108484543B (en) | Preparation method of potassium dehydroandrographolide succinate or potassium dehydroandrographolide succinate | |
| US5922849A (en) | Process for preparation of N-demethyl-4"-deoxy-erthromycins A and B | |
| IL156463A (en) | Process for the preparation of 25-cyclohexyl-22,23-dihydro-5-oxoavermectin b1 | |
| CN110563784B (en) | Synthetic method of emamectin benzoate crude product | |
| KR20150084165A (en) | Method for preparing of nafamostat mesilate | |
| CN111138351A (en) | Synthetic method of 2-aminomethyl-3-chloro-5-trifluoromethylpyridine acetate | |
| CN114717280A (en) | Synthesis method of monopilavir | |
| CN113004245B (en) | Preparation method of desloratadine | |
| CN109651234B (en) | Synthesis method of donepezil hydrochloride | |
| CN111574458A (en) | Synthetic method of ergothioneine | |
| CN113233998B (en) | Preparation method of mesotrione | |
| CN108997454B (en) | Chemical synthesis method of beta-arbutin | |
| CN115772136A (en) | Preparation method of parecoxib sodium and intermediate thereof | |
| CN112225736A (en) | Preparation method of 6-bromoimidazo [1.2-a ] pyridine-3-formaldehyde | |
| RU2351604C1 (en) | Method of producing 2,3-monoacetonide 20-hydroxyecdysone | |
| CN115477618A (en) | Synthesis method of benzyl triazole | |
| CN117417398A (en) | Preparation method of ivermectin | |
| WO2023078722A1 (en) | Synthesis of pantothenic acid butyrate | |
| CN115894374A (en) | Preparation method and application of fluorocarbonitrile | |
| KR20220044684A (en) | Salicylamine Acetate Preparation Method | |
| CN117586151A (en) | Industrial production method of efficient Fmoc-Asp (OtBu) -OH | |
| CN114105908A (en) | Preparation method of key intermediate of tetrahydronaphthalene benzamide |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20210608 |