CN108299345B - Preparation method of alpha-acetyl-gamma-butyrolactone - Google Patents
Preparation method of alpha-acetyl-gamma-butyrolactone Download PDFInfo
- Publication number
- CN108299345B CN108299345B CN201810135352.6A CN201810135352A CN108299345B CN 108299345 B CN108299345 B CN 108299345B CN 201810135352 A CN201810135352 A CN 201810135352A CN 108299345 B CN108299345 B CN 108299345B
- Authority
- CN
- China
- Prior art keywords
- butyrolactone
- gamma
- acetyl
- alpha
- preparing
- 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.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/32—Oxygen atoms
- C07D307/33—Oxygen atoms in position 2, the oxygen atom being in its keto or unsubstituted enol form
Abstract
A preparation method of alpha-acetyl-gamma-butyrolactone belongs to the technical field of compound synthesis, and comprises the following steps: under the condition of organic solvent, gamma-butyrolactone and acetaldehyde are used as initial raw materials, inorganic base is used as catalyst, acetylation reaction is carried out, the pH value of reaction liquid is regulated to be neutral by dilute acid, and then post-treatment is carried out to obtain alpha-acetyl-gamma-butyrolactone. The method has the characteristics of economy, feasibility, high yield, safety, environmental protection and suitability for industrialization.
Description
Technical Field
The invention belongs to the technical field of compound synthesis, and particularly relates to a method for preparing alpha-acetyl-gamma-butyrolactone.
Background
The alpha-acetyl-gamma-butyrolactone is an important chemical intermediate, and can be used for preparing 3-mercapto-4-oxo-amyl acetate, cyclopropylamine, bactericide prothioconazole, anticonvulsant and sedative hypnotic drugs chlormethiazide hydrochloride, chlorophyll, nystagmus, chloroquine, antipsychotic drugs risperidone, paliperidone, partial perfume and the like. Alpha-acetyl-gamma-butyrolactone is also a good drug analysis reagent, can generate a color reaction with primary amine or sulfonamides, and is commonly used for the analysis of the drug preparations. Meanwhile, the alpha-acetyl-gamma-butyrolactone also has the structural characteristic of beta-dicarbonyl and can perform complex reaction with a plurality of substances.
The synthetic process route of the alpha-acetyl-gamma-butyrolactone can be mainly divided into two processes, namely a process route taking ethylene oxide and ethyl acetoacetate as starting materials and a process route taking gamma-butyrolactone and ethyl acetate as starting materials. Because ethylene oxide belongs to a first-grade flammable and explosive chemical and has serious potential safety hazards in the storage, transportation and production links, domestic production enterprises do not adopt the process route, and usually adopt a process route taking gamma-butyrolactone and ethyl acetate as starting materials. Several routes to alpha-acetyl-gamma-butyrolactone by acylation of ethyl acetate and gamma-butyrolactone in the presence of strong bases (sodium metal, potassium metal, sodium alkoxide, sodium amide, etc.) are known in the art, and were originally reported by F, Korte et al (Angewandte Chemie,71, 1959, 23, 709-752). The sodium metal is used as a catalyst to catalyze the reaction of ethyl acetate and gamma-butyrolactone at the temperature of 100 ℃ and 105 ℃ in the presence of a toluene solvent, as reported in Chinese patents CN1548427A and CN101768141A, the yield is good and the cost is low, so that the method has great potential safety hazards, but is still a main process route adopted by domestic production enterprises at present. Chinese patent CN101092407B reports that alpha-acetyl-gamma-butyrolactone is synthesized by carrying out acylation reaction on ethyl acetate and gamma-butyrolactone under gas phase catalysis of a fluorine-alkali solid-phase catalyst, and although the potential safety hazard is solved, the problems of high cost and product quality caused by high energy consumption are solved, and the method is not adopted by production enterprises at present. In addition, the current process using metallic sodium as a catalyst usually generates a waste solvent of ternary azeotropic mixture of ethyl acetate, ethanol and toluene.
Japanese patent 45/009538 reports that acylation reaction of butyl acetate and gamma-butyrolactone is catalyzed by solid sodium butoxide, while acylation reaction of ethyl acetate and gamma-butyrolactone is catalyzed by solid sodium methoxide in Japanese patent 58/099473, but because of the use of high boiling point solvents, the high boiling point solvents have the problem of being difficult to remove, resulting in low product yield, and the recovery of reaction materials is not concerned in the patent, therefore the method has not been industrially applied on a large scale. Meanwhile, in the reaction process of japanese patent 58/099473, the feeding molar ratio of solid sodium methoxide to liquid gamma-butyrolactone needs to be strictly controlled, while solid sodium methoxide belongs to powdery solid, the feeding speed is not easy to control and dust is easily generated, the viscosity of sodium sulfate solid generated in the reaction after filtering and adjusting pH in the post-treatment process is large, the filtering is difficult, meanwhile, part of feed liquid is carried in the sodium sulfate solid with large viscosity, the washing is not thorough, the product yield is affected, the boiling points of alcohol and ester of the raw materials are low, the subsequent high-pressure reaction is needed to completely carry out the reaction, and the continuous reactor and the high-pressure reactor (the reaction pressure can reach 4-7Mpa) are high in equipment requirement, high in investment cost and strict in operation technical requirement, so that the continuous reactor and the high-pressure reactor are not. The method takes metallic sodium as a catalyst to catalyze acetate and gamma-butyrolactone to react at 105 ℃ in the presence of a toluene solvent, as reported in Chinese patent CN1548427, the yield is good and the cost is low, and although there is a great potential safety hazard (explosion or fire accident caused by improper treatment of metallic sodium), the method is still a main process route adopted by domestic production enterprises at present. Although there are new chinese patent reports trying to reduce the safety hazard of the process by adding metallic sodium and controlling the reaction process (for example, chinese patent CN101768141 reports adding metallic sodium by batch and CN102030729 reports adding metallic sodium with a certain specific surface area by one-time), since the process route necessarily uses metallic sodium, the problem of the safety hazard cannot be solved fundamentally in nature.
Disclosure of Invention
The invention overcomes the defects in the prior art and provides the preparation method of the alpha-acetyl-gamma-butyrolactone, which is economical, feasible, high in yield, safe, environment-friendly and suitable for industrialization.
The invention aims to realize the preparation method of the alpha-acetyl-gamma-butyrolactone, which comprises the steps of carrying out acetylation reaction by using the gamma-butyrolactone and acetaldehyde as initial raw materials and using inorganic base as a catalyst under the condition of an organic solvent, adjusting the pH value of reaction liquid to be neutral by using dilute acid, and carrying out post-treatment to obtain the alpha-acetyl-gamma-butyrolactone.
The time of the acetylation reaction is 1-6h, and the preferable time of the acetylation reaction is 1.5-2 h; the molar ratio of the gamma-butyrolactone to acetaldehyde is 1:1-3, preferably 1: 1.2-1.5; the molar ratio of the gamma-butyrolactone to the inorganic base is 1:1-3, preferably 1: 1.5-2; the acid is selected from inorganic acid, and the inorganic acid is selected from one or more of hydrochloric acid and sulfuric acid; the concentration of the dilute acid is 30-80%, and the preferred concentration is 50%; the pH value is adjusted to be 6-7 when in neutralization; the temperature for adjusting the pH value is not more than 15 ℃; the post-treatment comprises the steps of stirring, filtering, washing, vacuum concentration and vacuum rectification; the temperature of the acetylation reaction is 50-120 ℃, and the preferable temperature of the acetylation reaction is 85-98 ℃; the acetylation reaction is carried out in an autoclave, and the pressure of the acetylation reaction is 0.1-1.0 MPa; the inorganic base is selected from one or more of sodium carbonate, sodium bicarbonate, potassium carbonate or potassium bicarbonate; the organic solvent is selected from one or more of ethyl acetate, butyl acetate, isopropyl acetate, methyl acetate, dichloromethane, chloroform or tetrahydrofuran; the stirring time is 6-8 hours, the stirring temperature is 20-35 ℃, and the reduced pressure concentration temperature is 65-75 ℃; before the acetylation reaction is carried out, the organic solvent, the gamma-butyrolactone, the acetaldehyde and the inorganic base are added in a feeding mode that the organic solvent and the inorganic base are added, then the gamma-butyrolactone and a mixed solution are added simultaneously, the mixed solution is formed by mixing the organic solvent and the acetaldehyde, and stirring is continued after the addition; controlling the dropping speed of the gamma-butyrolactone and the mixed solution, and ensuring that the adding speed is that the gamma-butyrolactone: the molar ratio of acetaldehyde is 1:1-1.2, and the addition is finished in 0.8-1.2 hours; the time of the continuous stirring is 20-40 minutes, and the temperature of the continuous stirring is 70-80 ℃; after the organic solvent and the inorganic base are added, the temperature is raised to 50-80 ℃, and then the gamma-butyrolactone and the mixed solution are added at the same time.
The reaction formula is shown as follows:
the key point of the invention is a preparation method of alpha-acetyl-gamma-butyrolactone. The principle is as follows: the method uses liquid acetaldehyde which is cheaper in industrial price as an acylation reagent for reaction, and the product yield can be high by properly controlling the molar ratio of added feed liquid and the temperature of reaction liquid. Secondly, use the inorganic base that industrial price is cheaper as the catalyst, in all throwing into the reaction flask in advance, the temperature of suitable control reaction liquid can, further reduced raw materials cost. The tertiary acetylation reaction process is carried out by using the most preferable reaction solvent such as ethyl acetate, the reaction temperature such as 85-90 ℃, the catalyst such as sodium bicarbonate and the more preferable reaction molar ratio, so that the product yield is high, the operation is simple and the method is suitable for industrial production.
Compared with the prior art, the preparation method of alpha-acetyl-gamma-butyrolactone has the characteristics of lower cost of raw material reagents acetaldehyde and inorganic base, lower requirements of used weak base on equipment selection, higher yield, lower reaction pressure, no solid sodium methoxide powder charging condition, safety, environmental protection, suitability for industrialization and the like, and is widely applied to the technical field of medicines.
Detailed Description
In order to further understand the present invention, the following examples are provided to illustrate the preparation of α -acetyl- γ -butyrolactone according to the present invention. It is to be understood that these examples are described merely to illustrate the features of the present invention in further detail, and not as limitations of the invention or of the scope of the claims appended hereto.
The first embodiment is as follows: preparation of alpha-acetyl-gamma-butyrolactone
Adding 150g of isopropyl acetate and 138.2g (1000.0mmol) of potassium carbonate into a 500mL three-necked bottle, heating to 70-74 ℃, simultaneously adding 43g (500.0mmol) of gamma-butyrolactone and a mixed solution (50g of isopropyl acetate and 26.4g (600.0mmol) of liquid acetaldehyde are uniformly mixed), controlling the dropping speed of the gamma-butyrolactone and the mixed solution, and ensuring that the adding speed is gamma-butyrolactone: the mixture was added in 1.63g to 1g (molar ratio of γ -butyrolactone to acetaldehyde was 1:1.2) over 1 h. After the addition of the materials was completed, the mixture was stirred at 80 ℃ for 30min to remove the gas generated during the reaction. And (2) pressing the reaction solution into a 500mL high-pressure kettle, carrying out acetylation reaction at 94-98 ℃ for 1.5h, keeping the pressure within the range of 0.1-1.0MPa after the pressure is stabilized, introducing cooling water (10-25 ℃) to cool after the reaction is finished, discharging, washing the reaction kettle by using 20g of isopropyl acetate, and combining washing liquids into the reaction solution.
Controlling the temperature of the materials at 5-15 ℃, adjusting the pH value to 6-7 by using 50% sulfuric acid, wherein the temperature in the whole process of pH adjustment is not more than 15 ℃; a large amount of solid is separated out in the process of dripping 50 percent of sulfuric acid; after the pH is adjusted, stirring is continued for 6 to 8 hours at the temperature of between 20 and 35 ℃, and solid is removed by filtration. Washing the filter cake with 20g of isopropyl acetate for 2 times, combining washing liquid and filtrate, concentrating under reduced pressure at 70 ℃ until no liquid flows out, evaporating the solvent to obtain 53.2g of crude alpha-acetyl-gamma-butyrolactone with the content of 76%, and finally performing reduced pressure rectification to obtain 50.07g of crude alpha-acetyl-gamma-butyrolactone pure product with the gas phase purity of 99.3% and the yield of 77.69%.
Example two: preparation of alpha-acetyl-gamma-butyrolactone
Adding 100g of ethyl acetate and 63.0g (750.0mmol) of sodium bicarbonate into a 500mL three-necked bottle, heating to 60-65 ℃, simultaneously adding 43g (500.0mmol) of gamma-butyrolactone and a mixed solution, uniformly mixing the mixed solution (60g of ethyl acetate and 33.0g (750.0mmol) of liquid acetaldehyde), controlling the dropping speed of the gamma-butyrolactone and the mixed solution, and ensuring that the adding speed is gamma-butyrolactone: the mixture was added in 1.95g to 1g (molar ratio of γ -butyrolactone to acetaldehyde was 1:1) for 1 h. After the addition of the materials was completed, the stirring was continued at 70 ℃ for 30min to remove the gas generated during the reaction. And (2) pressing the reaction solution into a 500mL high-pressure kettle, performing acetylation reaction at 85-90 ℃ for 2h, keeping the pressure within the range of 0.1-1.0MPa after the pressure is stabilized, introducing cooling water (10-25 ℃) to cool after the reaction is finished, discharging, washing the reaction kettle by using 20g of ethyl acetate, and combining washing liquor into the reaction solution.
Controlling the temperature of the materials at 5-15 ℃, adjusting the pH value to 6-7 by using 50% sulfuric acid, wherein the temperature in the whole process of pH adjustment is not more than 15 ℃; a large amount of solid is separated out in the process of dripping 50 percent of sulfuric acid; after the pH is adjusted, stirring is continued for 6 to 8 hours at the temperature of between 20 and 35 ℃, and solid is removed by filtration. Washing the filter cake with 20g of ethyl acetate for 2 times, combining washing liquid and filtrate, concentrating under reduced pressure at 70 ℃ until no liquid flows out, evaporating the solvent to obtain 58.5g of crude alpha-acetyl-gamma-butyrolactone with the content of 78%, and finally performing reduced pressure rectification to obtain 51.42g of crude alpha-acetyl-gamma-butyrolactone pure product with the gas phase purity of 99.1% and the yield of 79.31%.
It will be understood that modifications and variations can be made by persons skilled in the art in light of the above teachings and all such modifications and variations are intended to be included within the scope of the invention as defined in the appended claims.
Claims (13)
1. A preparation method of alpha-acetyl-gamma-butyrolactone is characterized in that: under the condition of organic solvent, gamma-butyrolactone and acetaldehyde are used as initial raw materials, inorganic base is used as catalyst, acetylation reaction is carried out, the pH value of reaction liquid is regulated to 6-7 by using dilute acid, and then post-treatment is carried out to obtain alpha-acetyl-gamma-butyrolactone.
2. The method for preparing α -acetyl- γ -butyrolactone according to claim 1, wherein the acetylation reaction time is 1-6 h; the molar ratio of the gamma-butyrolactone to acetaldehyde is 1: 1-3; the molar ratio of the gamma-butyrolactone to the inorganic base is 1: 1-3.
3. The method for preparing α -acetyl- γ -butyrolactone according to claim 2, wherein the time of acetylation is 1.5-2 h; the molar ratio of the gamma-butyrolactone to acetaldehyde is 1: 1.2-1.5; the molar ratio of the gamma-butyrolactone to the inorganic base is 1: 1.5-2.
4. The method for preparing alpha-acetyl-gamma-butyrolactone according to claim 1, wherein said acid is selected from inorganic acids, said inorganic acids are selected from one or more of hydrochloric acid and sulfuric acid; the concentration of the dilute acid is 30-80%; the temperature during the pH adjustment is not more than 15 ℃.
5. The process according to claim 4, wherein the dilute acid concentration is 50%.
6. The method for preparing alpha-acetyl-gamma-butyrolactone according to claim 1, wherein the post-treatment comprises the steps of stirring, filtering, washing, vacuum concentration, and vacuum rectification.
7. The method for preparing alpha-acetyl-gamma-butyrolactone according to claim 1, wherein the temperature of acetylation reaction is 50-120 deg.C; the acetylation reaction is carried out in an autoclave, and the pressure of the acetylation reaction is 0.1-1.0 MPa.
8. The process according to claim 7, wherein the acetylation reaction is carried out at a temperature of 85 to 98 ℃.
9. The method for preparing alpha-acetyl-gamma-butyrolactone according to claim 1, wherein said inorganic base is selected from one or more of sodium carbonate, sodium bicarbonate, potassium carbonate and potassium bicarbonate.
10. The method for preparing alpha-acetyl-gamma-butyrolactone according to claim 1, wherein said organic solvent is selected from one or more of ethyl acetate, butyl acetate, isopropyl acetate, methyl acetate, dichloromethane, chloroform or tetrahydrofuran.
11. The method for preparing α -acetyl- γ -butyrolactone according to claim 6, wherein the stirring time is 6-8 hours, the stirring temperature is 20-35 ℃, and the reduced pressure concentration temperature is 65-75 ℃.
12. The method for preparing α -acetyl- γ -butyrolactone according to claim 1, wherein the organic solvent, γ -butyrolactone, acetaldehyde and inorganic base are added before the acetylation reaction, and then the γ -butyrolactone and the mixed solution are added simultaneously, wherein the mixed solution is prepared by mixing the organic solvent and acetaldehyde, and then the stirring is continued after the addition.
13. The method for preparing α -acetyl- γ -butyrolactone according to claim 12, wherein the dropping rate of γ -butyrolactone and the mixed solution is controlled to ensure that the dropping rate is γ -butyrolactone: the molar ratio of acetaldehyde is 1:1-1.2, and the addition is finished in 0.8-1.2 hours; the time of the continuous stirring is 20-40 minutes, and the temperature of the continuous stirring is 70-80 ℃; after the organic solvent and the inorganic base are added, the temperature is raised to 50-80 ℃, and then the gamma-butyrolactone and the mixed solution are added at the same time.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810135352.6A CN108299345B (en) | 2018-02-09 | 2018-02-09 | Preparation method of alpha-acetyl-gamma-butyrolactone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810135352.6A CN108299345B (en) | 2018-02-09 | 2018-02-09 | Preparation method of alpha-acetyl-gamma-butyrolactone |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108299345A CN108299345A (en) | 2018-07-20 |
| CN108299345B true CN108299345B (en) | 2021-06-11 |
Family
ID=62864977
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810135352.6A Active CN108299345B (en) | 2018-02-09 | 2018-02-09 | Preparation method of alpha-acetyl-gamma-butyrolactone |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108299345B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112759566B (en) * | 2020-12-31 | 2023-05-02 | 江苏兄弟维生素有限公司 | Application of liquid sodium methoxide in synthesis of alpha-acetyl-gamma-butyrolactone and synthesis method of alpha-acetyl-gamma-butyrolactone |
| CN114835661A (en) * | 2022-05-07 | 2022-08-02 | 南京杰运医药科技有限公司 | Industrial preparation method of a-acetyl-r-butyrolactone |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3823668B2 (en) * | 2000-03-08 | 2006-09-20 | ダイソー株式会社 | Sphingomyelin analogs and methods for their production |
| WO2005014565A2 (en) * | 2003-08-07 | 2005-02-17 | E.I. Dupont De Nemours And Company | Cis-3,5-disubstituted-dihydro-furan-2-ones and the preparation and use thereof |
| CN101092407B (en) * | 2007-07-27 | 2010-05-19 | 泰州延龄精细化工有限公司 | Method for preparing alpha - acetyl - gamma - butyrolactone |
| CN101230054A (en) * | 2008-02-04 | 2008-07-30 | 吴江信谊化工有限公司 | Method for preparing alpha-acetyl-gamma-butyrolactone |
| CN103387556A (en) * | 2012-05-08 | 2013-11-13 | 江苏兄弟维生素有限公司 | Synthetic method for alpha-acetyl-gamma-butyrolactone |
-
2018
- 2018-02-09 CN CN201810135352.6A patent/CN108299345B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN108299345A (en) | 2018-07-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102229586B (en) | Preparation method for alpha-acetyl-gamma-butyrolactone | |
| CN108299345B (en) | Preparation method of alpha-acetyl-gamma-butyrolactone | |
| CN108129288B (en) | Synthesis method of trans-3-hydroxycyclobutylformic acid | |
| CN109776337A (en) | The preparation method of 2- methoxyl group -4- nitroaniline | |
| CN107827800B (en) | Method for preparing zeaxanthin crystals from wastewater-free marigold oleoresin | |
| CN110804031B (en) | Synthetic method of alpha-acetyl-gamma-butyrolactone | |
| CN111620844B (en) | Preparation method of alpha-acetyl-gamma-butyrolactone | |
| CN101186603A (en) | Process for preparing tetramethyl glycolide | |
| CN112028788A (en) | Preparation method for continuously preparing tert-butyl hydrazine hydrochloride | |
| CN104151251A (en) | Method for one-pot synthesis of 5-acetylacetamido-benzimidazolone | |
| CN108484439B (en) | Preparation method of alpha-formyl-beta-formamido propionitrile alkali metal salt | |
| CN101619064B (en) | Synthesis and process method for novel polynitrogen heterocycle pharmaceutical intermediates | |
| CN106749235B (en) | The preparation method of poly-substituted quinoline and azole derivatives | |
| CN112266390B (en) | Preparation method of Barosavir intermediate | |
| CN114478216A (en) | Novel synthesis method of 1-acetyl-1-chlorocyclopropane | |
| CN112142750A (en) | Process for preparing 4, 7-dihydro- [1, 2, 4] triazolo [1, 5-a ] pyrimidine derivatives as pharmaceutical intermediates | |
| CN101830820A (en) | Method for preparing 2,5-diparamethylaniline terephthalic acid (DTTA) | |
| CN111470970A (en) | Preparation method of p-substituted benzyl alcohol | |
| CN101443310A (en) | Process for continuously preparing n- ethyl-2-pyrrolidone (NEP) | |
| CN107325049B (en) | Preparation method of neratinib intermediate | |
| CN114671810B (en) | Preparation method of imidazole phenylurea | |
| CN112679440A (en) | Preparation method of 5-n-butyl-2-ethylamino-4-hydroxy-6-methylpyrimidine | |
| CN113956258B (en) | Preparation method of indolo [2,3-A ] carbazole by adopting acidic ionic liquid | |
| CN103483283A (en) | Synthesis method for antioxidant 1790 | |
| CN110028379B (en) | Preparation method of 4, 4' -dichloromethyl biphenyl |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20230812 Address after: No. 20-4, Shenxi Fourth East Road, Shenyang Economic and Technological Development Zone, Shenyang City, Liaoning Province, 110142 Patentee after: SHENYANG DONGRUI FINE CHEMICAL Co.,Ltd. Address before: 110027 8 Kunming Hu Street, Shenyang economic and Technological Development Zone, Liaoning Patentee before: Northeast Pharmaceutical Group Co.,Ltd. Patentee before: SHENYANG DONGRUI FINE CHEMICAL Co.,Ltd. |
|
| TR01 | Transfer of patent right |