CN114436924B - Synthesis method of hydroxy pinacolone retinoic acid ester - Google Patents
Synthesis method of hydroxy pinacolone retinoic acid ester Download PDFInfo
- Publication number
- CN114436924B CN114436924B CN202210156402.5A CN202210156402A CN114436924B CN 114436924 B CN114436924 B CN 114436924B CN 202210156402 A CN202210156402 A CN 202210156402A CN 114436924 B CN114436924 B CN 114436924B
- Authority
- CN
- China
- Prior art keywords
- retinoic acid
- hydroxy
- mass
- acid ester
- reaction
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C403/00—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone
- C07C403/20—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by carboxyl groups or halides, anhydrides, or (thio)esters thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the technical field of fine organic synthesis, and particularly relates to a synthesis method of hydroxy pinacolone retinoic acid ester. The method comprises the following steps: (1) Adding an organic solvent into retinoic acid, adding an amide catalyst, stirring uniformly, and then carrying out ice bath; (2) Adding phosphorus trichloride into the material obtained in the step (1) under the protection of nitrogen, and reacting; (3) Standing to separate out lower inorganic solution, adding 1-hydroxy-3, 3-dimethylbutane-2-one under ice bath condition, adding acid binding agent, reacting under heat preservation, vacuum filtering inorganic salt, concentrating liquid phase under reduced pressure; (4) Adding recrystallization solvent, cooling and crystallizing to obtain hydroxy pinacolone retinoic acid ester. The raw materials and the reagents adopted by the invention are all common chemical reagents, so that the cost is low and the method is easy to obtain; the solvent used in the reaction is toluene, and the next reaction can be carried out without separation and purification; the two-step reaction can be completed in the same kettle, the use of equipment is less, and the equipment utilization rate is high.
Description
Technical Field
The invention belongs to the technical field of fine organic synthesis, and particularly relates to a synthesis method of hydroxy pinacolone retinoic acid ester.
Background
Vitamin A is also known as retinol, is a natural fat-soluble vitamin, and the generalized vitamin A also comprises retinol derivatives such as retinol, retinoic acid, retinol acetate, retinol palmitate and the like, and various structures can be mutually converted. Vitamin a plays an important role in the growth, development, vision, immunization, etc. of vertebrates. In recent years, scientists have found that vitamin a has a great therapeutic effect on preventing and treating skin problems such as skin aging, and has paid attention to as an active ingredient for preventing and repairing skin aging, and has been used in various external preparations for skin diseases and often added to cosmetics. Vitamin A is extremely unstable due to the fact that molecules have long electron-rich conjugated polyene chains, and is easy to damage when meeting acid, oxide, high temperature and ultraviolet rays. To avoid its deactivation, it is often chemically modified to an ester derivative of vitamin a. The research shows that the vitamin A ester derivative not only has various physiological functions of vitamin A, but also has higher stability and wider application range. Common vitamin A ester derivatives are vitamin A acetate, vitamin A palmitate and the like. However, the existing ester derivatives have the defects of high irritation, low conversion efficiency and the like, so that the development of some products with low irritation to skin and high conversion rate has important significance.
The hydroxy pinacolone retinoic acid ester belongs to one of vitamin A ester derivatives, is an ester of vitamin A acid of a new generation, and can directly act without conversion unlike other vitamin A acid derivatives, and the principle is similar to that of all-trans A acid. Compared with tretinoin, the irritation of hydroxy pinacolone retinoic acid ester is reduced, and the use is safer around eyes, and the transdermal rate is more excellent.
Regarding the synthesis of hydroxy pinacolone retinoic acid esters, the following patent documents disclose:
CN112522331a discloses a bio-enzyme catalyzed synthesis of hydroxy pinacolin retinoic acid ester, which is prepared by reacting retinoic acid ester with 1-hydroxy-3, 3-dimethylbutan-2-one as raw material in an aqueous buffer solution containing acyltransferase with pH of 7.0-10.0. The above method has some drawbacks such as: the biological enzyme has poor environmental adaptability, strict production environment requirement, higher enzyme price and relatively higher production cost, thereby limiting the large-scale industrial production of the product.
CN113149880a provides a method for preparing hydroxy pinacolone retinoic acid ester, which adopts chloro pinacolone to prepare corresponding pinacolone through hydrolysis reaction under strong alkaline condition, and then the pinacolone and tretinoin are obtained through condensation reaction under condensing agent and catalyst condition. In the process, DCC dehydrating agent used in condensation reaction generates DCU solid waste after the reaction is finished, the inventor roughly calculates that 900KG solid waste is generated per ton of product produced, the cost is close to one ton, and the three-waste treatment cost is high. DCU and DMAP are not easy to remove, residues exist in the product, a large amount of wastewater is generated by washing with an acidic aqueous solution, or the DCU and DMAP are removed by adopting a chromatographic column method, and if the DCU and DMAP are removed by adopting the chromatographic column method, the production efficiency is low and the cost is high.
Therefore, the improvement on the method is needed, and the production method of the hydroxy pinacolone retinoic acid ester has the advantages of simple process, low production cost and high total yield of products.
Disclosure of Invention
In order to solve the technical problems, the invention provides a production method of hydroxy pinacolone retinoic acid ester, which has the advantages of simple process, low production cost and high total yield of products.
The invention is completed by the following technical scheme: the production method comprises the steps of using retinoic acid and 1-hydroxy-3, 3-dimethylbutan-2-one as raw materials, carrying out acylation and esterification to obtain a crude product, and carrying out refining crystallization to obtain a finished product, wherein the production method comprises the following steps:
(1) Adding an organic solvent into retinoic acid, adding an amide catalyst, stirring uniformly, and then carrying out ice bath;
(2) Adding phosphorus trichloride into the material obtained in the step (1) under the protection of nitrogen, and reacting;
(3) After the reaction in the step (2) is completed, standing to separate out a lower inorganic solution, adding 1-hydroxy-3, 3-dimethylbutane-2-one under the ice bath condition, adding an acid binding agent, and carrying out heat preservation reaction; after the reaction is finished, the inorganic salt is filtered by vacuum filtration, and the liquid phase is concentrated by vacuum filtration to obtain a yellow oily crude product;
(4) Adding a recrystallization solvent into the yellow oily crude product obtained in the step (3), and cooling and crystallizing to obtain the hydroxy pinacolone retinoic acid ester.
The main chemical reaction equation is as follows:
preferably, in (1), the amide catalyst is N, N-dimethylformamide; the molar ratio of the amide catalyst to the apparent Huang Suanma is 0.1-0.5: 1, a step of; the organic solvent is toluene, and the molar ratio of toluene to retinoic acid is 15-20: 1, a step of; after stirring uniformly, controlling the temperature of the system in an ice bath at 5-15 ℃;
(2) Adding phosphorus trichloride into the ice-bath system in step (1) dropwise under the protection of nitrogen by utilizing a constant-pressure dropping funnel, after the dropwise addition, heating the system to 20-40 ℃, and preserving the temperature for 5-7 h, wherein the molar ratio of retinoic acid to phosphorus trichloride is 1:0.6-1. The proportion range of retinoic acid and phosphorus trichloride is the key point to be protected in the invention, and the prepared hydroxy pinacolone retinoic acid ester has high purity and less impurities by adjusting the proportion of retinoic acid and phosphorus trichloride.
Preferably, in the step (3), whether the reaction is complete is judged by detection of a liquid chromatograph, if the reaction is complete, 1-hydroxy-3, 3-dimethylbutan-2-one is dripped under the ice bath condition, the temperature is raised to 20-35 ℃ after the dripping is finished, the constant pressure dripping funnel is used for slowly dripping the acid binding agent, and the temperature is kept for 5-7 hours after the dripping is finished.
(3) In (3), controlling the mol ratio of retinoic acid to 1-hydroxy-3, 3-dimethylbutan-2-one to be 1: 1.2-2, wherein the mol ratio of retinoic acid to acid binding agent is 1:1.2 to 3; the acid binding agent is at least one of triethylamine, pyridine and sodium hydroxide;
(4) The recrystallization solvent is at least one of methanol, absolute ethyl alcohol and isopropanol; the volume ratio of the recrystallization solvent to the concentrated solution is 2-4:1.
Compared with the synthesis method reported in the prior patent document, the synthesis method disclosed by the invention has the following remarkable advantages:
(1) The raw materials and the reagents used in the invention are all commonly used chemical reagents, and are easy to obtain, low in price and low in production cost;
(2) The organic solvent adopted in the step (1) in the extraction process is toluene, and the steps are that
(3) During the reaction, the toluene remained in the upper mixed solution can still be continuously used as a solvent, and the next reaction can be carried out without separating and purifying the toluene, so that the procedure of the reaction operation is greatly simplified, and the complicated extraction step caused by the need of purifying by adopting different solvents is avoided;
(3) The product of the invention has stable income, the total yield after two steps of reaction can reach 92 percent, and the purity can reach 99.8 percent;
(4) The two-step reaction in the steps (1) and (3) can be completed in the same kettle, the equipment is few, the equipment utilization rate is high, the material transfer and the intermediate refining and purifying are reduced as much as possible, and excellent basic production conditions are provided for large-scale industrial production.
Drawings
FIG. 1 is a physical diagram of the product of the invention, hydroxypinacolone retinoic acid ester;
FIG. 2 is a diagram showing the nuclear magnetic spectrum of the product of example 2 of the present invention;
FIG. 3 is a liquid chromatogram of the product of example 2;
fig. 4-13 are liquid chromatograms of different batches of product prepared using the method of the present invention.
Detailed Description
The present invention will now be further described in connection with specific embodiments in order to enable those skilled in the art to better understand the invention.
Example 1
A method for synthesizing hydroxy pinacolone retinoic acid ester, comprising the steps of:
s1: 20g (0.07 mol) of retinoic acid, 100g (1.09 mol) of toluene and 1g (0.014 mol) of N, N-dimethylformamide are sequentially added into a 250ml three-neck flask, and after uniform stirring, the temperature of the system is reduced to about 10 ℃ by an ice bath;
s2: 5.8g (0.042 mol) of phosphorus trichloride is added into the flask dropwise under the protection of nitrogen by utilizing a constant pressure dropping funnel, after the dropping is finished, the temperature of the system is raised to 25 ℃, and the temperature is kept for 6 hours;
s3: after the reaction is detected to be complete by a liquid chromatograph, standing to separate out a lower inorganic solution, beginning to dropwise add 10.5g (0.09 mol) of 1-hydroxy-3, 3-dimethylbutane-2-one under ice bath condition, heating to room temperature after the completion of the dropwise addition, slowly dropwise adding 7.3g (0.07 mol) of triethylamine by using a constant pressure dropping funnel, keeping the temperature for 6 hours after the completion of the dropwise addition, filtering inorganic salt under reduced pressure, concentrating the liquid phase under reduced pressure to obtain a yellow oily crude product;
s4: 50ml of absolute ethyl alcohol is added into the yellow oily crude product obtained in the step S3 to be cooled and crystallized, and 20.3g of yellow solid powder is obtained. The total yield of the product hydroxylbenzone retinoic acid ester is 73% after conversion, and the purity of the product is 99.3% after HPLC detection.
Example 2
A method for synthesizing hydroxy pinacolone retinoic acid ester, comprising the steps of:
s1: 20g (0.07 mol) of retinoic acid, 100g (1.09 mol) of toluene and 2g (0.028 mol) of N, N-dimethylformamide are sequentially added into a 250ml three-neck flask, and after uniform stirring, the temperature of the system is reduced to about 10 ℃ by an ice bath;
s2: 6.7g (0.049 mol) of phosphorus trichloride is added into the flask dropwise under the protection of nitrogen by utilizing a constant pressure dropping funnel, after the dropping is finished, the temperature of the system is raised to 30 ℃, and the temperature is kept for 6 hours;
s3: after the reaction is detected to be complete by a liquid chromatograph, standing to separate out a lower inorganic solution, beginning to dropwise add 10.5g (0.09 mol) of 1-hydroxy-3, 3-dimethylbutane-2-one under ice bath condition, after the dropwise addition is completed, slowly dropwise adding 8.5g (0.084 mol) of triethylamine by using a constant pressure dropping funnel to room temperature, after the dropwise addition is completed, carrying out heat preservation reaction for 6 hours, carrying out vacuum filtration on inorganic salt after the reaction is completed, concentrating a liquid phase under reduced pressure to obtain a yellow oily crude product;
s4: 50ml of methanol was added to the yellow oily crude product obtained in S3, and the mixture was cooled and crystallized to obtain 25.6g of yellow solid powder, the purity of which was 99.8% as measured by HPLC.
The total yield of the product, hydroxy-pinacolone retinoic acid ester, was 92% by conversion.
The physical diagram of the product is shown in fig. 1, the nuclear magnetic spectrum characterization is shown in fig. 2, and the detected product is hydroxy pinacolone retinoic acid ester with the purity reaching 99.8% as can be seen from the liquid chromatogram 3.
TABLE 1HPLC detection results
Example 3
A method for synthesizing hydroxy pinacolone retinoic acid ester, comprising the steps of:
s1: 20g (0.07 mol) of retinoic acid, 100g (1.09 mol) of toluene and 2g (0.028 mol) of N, N-dimethylformamide are sequentially added into a 250ml three-neck flask, and after uniform stirring, the temperature of the system is reduced to about 10 ℃ by an ice bath;
s2: 6.7g (0.049 mol) of phosphorus trichloride is added into the flask dropwise under the protection of nitrogen by utilizing a constant pressure dropping funnel, after the dropping is finished, the temperature of the system is raised to 30 ℃, and the temperature is kept for 6 hours;
s3: after the reaction is detected to be complete by a liquid chromatograph, standing to separate out a lower inorganic solution, beginning to dropwise add 10.5g (0.09 mol) of 1-hydroxy-3, 3-dimethylbutane-2-one under ice bath condition, after the dropwise addition is completed, slowly dropwise adding 7.1g (0.07 mol) of triethylamine by using a constant pressure dropping funnel, after the dropwise addition is completed, carrying out heat preservation reaction for 6 hours, after the reaction is completed, carrying out vacuum filtration on inorganic salt under reduced pressure, concentrating a liquid phase under reduced pressure to obtain a yellow oily crude product;
s4: 60ml of absolute ethyl alcohol is added into the yellow oily crude product obtained in the step S3 to be cooled and crystallized, and 23.4g of yellow solid powder is obtained.
The total yield of the product hydroxylbenzone retinoic acid ester is 84% after conversion, and the purity of the product is 98.8% after HPLC detection.
Example 4
A method for synthesizing hydroxy pinacolone retinoic acid ester, comprising the steps of:
s1: 20g (0.07 mol) of retinoic acid, 100g (1.09 mol) of toluene and 2g (0.028 mol) of N, N-dimethylformamide are sequentially added into a 250ml three-neck flask, and after uniform stirring, the temperature of the system is reduced to about 10 ℃ by an ice bath;
s2: 6.7g (0.049 mol) of phosphorus trichloride is added into the flask dropwise under the protection of nitrogen by utilizing a constant pressure dropping funnel, after the dropping is finished, the temperature of the system is raised to 30 ℃, and the temperature is kept for 6 hours;
s3: after the reaction is detected to be complete by a liquid chromatograph, standing to separate out a lower inorganic solution, beginning to dropwise add 9.8g (0.084 mol) of 1-hydroxy-3, 3-dimethylbutane-2-one under ice bath condition, after the dropwise addition is completed, slowly dropwise adding 14.6g (0.14 mol) of triethylamine by using a constant pressure dropping funnel, after the dropwise addition is completed, carrying out heat preservation reaction for 6 hours, after the reaction is completed, carrying out vacuum filtration on inorganic salt, concentrating a liquid phase under reduced pressure to obtain a yellow oily crude product;
s4: 60ml of absolute ethyl alcohol is added for cooling and crystallization, and 21.8g of yellow solid powder is obtained.
The total yield of the product hydroxylbenzone retinoic acid ester is 82% after conversion, and the purity of the product is 99.4% after HPLC detection.
Example 5
A method for synthesizing hydroxy pinacolone retinoic acid ester, comprising the steps of:
s1: 20g (0.07 mol) of retinoic acid, 100g (1.09 mol) of toluene and 2g (0.028 mol) of N, N-dimethylformamide are sequentially added into a 250ml three-neck flask, and after uniform stirring, the temperature of the system is reduced to about 10 ℃ by an ice bath;
s2: 7.7g (0.056 mol) of phosphorus trichloride is added into the flask dropwise under the protection of nitrogen by utilizing a constant pressure dropping funnel, after the dropping is finished, the temperature of the system is raised to 25 ℃, and the temperature is kept for 6 hours;
s3: after the reaction is detected to be complete by a liquid chromatograph, standing to separate out a lower inorganic solution, beginning to dropwise add 9.8g (0.084 mol) of 1-hydroxy-3, 3-dimethylbutane-2-one under ice bath condition, after the dropwise addition is completed, slowly dropwise adding 8.5g (0.084 mol) of triethylamine by using a constant pressure dropping funnel, after the dropwise addition is completed, carrying out heat preservation reaction for 6 hours, after the reaction is completed, carrying out vacuum filtration on inorganic salt, concentrating a liquid phase under reduced pressure to obtain a yellow oily crude product;
s4: 50ml of isopropanol was added to the mixture to carry out cooling crystallization, thereby obtaining 21.2g of yellow solid powder.
The total yield of the product hydroxylbenzone retinoic acid ester is 76% after conversion, and the purity of the product is 98.8% after HPLC detection.
The product yields and purities in examples 1 to 5 are shown in the following table in tabular form:
table 2 the yields and purities (%)
| Example 1 | Example 2 | Example 3 | Example 4 | Example 5 | Comparative example 1 | Comparative example 2 | |
| Total yield of | 73 | 92 | 84 | 82 | 76 | 36 | 21.53 |
| Purity of | 99.3 | 99.8 | 98.8 | 99.4 | 98.8 | 97.6 | 94.6 |
The total yield refers to the yield of the final product, hydroxy-fundamental-frequency pinacol retinoic acid ester.
Comparative example 1
A method for synthesizing hydroxy pinacolone retinoic acid ester, comprising the steps of:
s1: 20g (0.07 mol) of retinoic acid, 100g (1.09 mol) of toluene and 2g (0.028 mol) of N, N-dimethylformamide are sequentially added into a 250ml three-neck flask, and after uniform stirring, the temperature of the system is reduced to about 10 ℃ by an ice bath;
s2: adding 9.2g (0.077 mol) of thionyl chloride into a flask dropwise under the protection of nitrogen by using a constant pressure dropping funnel, heating the system to 25 ℃ after the addition, and preserving the heat for 6 hours;
s3: after the reaction is detected to be complete by a liquid chromatograph, after the thionyl chloride is removed under reduced pressure, 9.8g (0.084 mol) of 1-hydroxy-3, 3-dimethylbutane-2-one is dripped under ice bath condition, the temperature is raised to the room temperature after the dripping is finished, 14.6g (0.14 mol) of triethylamine is slowly dripped by a constant pressure dripping funnel, the temperature is kept for 6 hours after the dripping is finished, after the reaction is finished, inorganic salt is filtered under reduced pressure, and the liquid phase is concentrated under reduced pressure to obtain a yellow oily crude product;
s4: 50ml of absolute ethyl alcohol is added for cooling and crystallization, and 10g of yellow solid powder is obtained.
The total yield of the product hydroxylbenzone retinoic acid ester is 36% after conversion, and the purity of the product is 97.6% after HPLC detection.
Comparative example 2
A method for synthesizing hydroxy pinacolone retinoic acid ester, comprising the steps of:
s1: 20g (0.07 mol) of retinoic acid, 100g (1.09 mol) of toluene and 2g (0.028 mol) of N, N-dimethylformamide are sequentially added into a 250ml three-neck flask, and after uniform stirring, the temperature of the system is reduced to about 10 ℃ by an ice bath;
s2: 6.9g (0.05 mol) of phosphorus trichloride is added into the flask dropwise under the protection of nitrogen by utilizing a constant pressure dropping funnel, after the dropping is finished, the temperature of the system is raised to 30 ℃, and the temperature is kept for 6 hours;
s3: after the reaction is detected to be complete by a liquid chromatograph, standing to separate out an inorganic solution at the lower layer, adding 2.8g (0.07 mol) of sodium hydroxide into the mixture, beginning to dropwise add 9.8g (0.084 mol) of 1-hydroxy-3, 3-dimethylbutane-2-one under the ice bath condition, keeping the temperature at 30 ℃ for reaction for 6 hours after the dropwise addition, filtering inorganic salt under reduced pressure after the reaction is finished, concentrating the liquid phase under reduced pressure to obtain a yellow oily crude product;
s4: 50ml of absolute ethyl alcohol is added for cooling and crystallization, and 6g of yellow solid powder is obtained.
The total yield of the product hydroxypinacolone retinoic acid ester is 21.53% after conversion, and the purity of the product is 94.6% after HPLC detection.
Example 6
The inventor also detects products in different batches respectively, and a liquid chromatogram is shown in figures 4-13;
TABLE 3 sample 1 liquid chromatography detection results
TABLE 4 sample 2 liquid chromatography detection results
TABLE 5 sample 3 liquid chromatography detection results
TABLE 6 sample 4 liquid chromatography detection results
TABLE 7 sample 5 liquid chromatography detection results
TABLE 8 sample 6 liquid chromatography detection results
TABLE 9 sample 7 liquid chromatography detection results
TABLE 10 sample 8 liquid chromatography detection results
TABLE 11 sample 9 liquid chromatography detection results
TABLE 12 sample 10 liquid chromatography detection results
From the above table and the liquid chromatogram of each batch of samples, it can be seen that the yield and purity of the hydroxy pinacolone retinoic acid ester obtained by the preparation method of the present invention are high.
Claims (1)
1. A synthesis method of hydroxy pinacolone retinoic acid ester comprises the following steps:
(1) Sequentially adding 20g of retinoic acid with the mass of 0.07mol of substances, 100g of toluene with the mass of 1.09mol of substances and 2g of N, N-dimethylformamide with the mass of 0.028mol of substances into a 250ml three-neck flask, uniformly stirring, and then cooling the system to 10 ℃ by an ice bath;
(2) Adding phosphorus trichloride with the mass of 6.7g and the mass of 0.049mol into a flask dropwise under the protection of nitrogen by utilizing a constant-pressure dropping funnel, and after the dropping is finished, raising the temperature of the system to 30 ℃ and preserving heat for 6 hours;
(3) After the reaction is detected to be complete by a liquid chromatograph, standing to separate out an inorganic solution at the lower layer, starting to dropwise add 1-hydroxy-3, 3-dimethylbutane-2-one with the mass of 10.5g and the mass of 0.09mol under the ice bath condition, after the completion of the dropwise addition, slowly adding triethylamine with the mass of 8.5g and the mass of 0.084mol by using a constant pressure dropping funnel to room temperature, after the completion of the dropwise addition, carrying out heat preservation reaction for 6 hours, carrying out vacuum filtration on inorganic salt under reduced pressure, and concentrating the liquid phase under reduced pressure to obtain a yellow oily crude product;
(4) And (3) adding 50ml of methanol into the yellow oily crude product obtained in the step (3) for cooling and crystallizing to obtain yellow solid powder of the hydroxy-pinacolone retinoic acid ester.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210156402.5A CN114436924B (en) | 2022-02-21 | 2022-02-21 | Synthesis method of hydroxy pinacolone retinoic acid ester |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210156402.5A CN114436924B (en) | 2022-02-21 | 2022-02-21 | Synthesis method of hydroxy pinacolone retinoic acid ester |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114436924A CN114436924A (en) | 2022-05-06 |
| CN114436924B true CN114436924B (en) | 2023-09-29 |
Family
ID=81372932
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210156402.5A Active CN114436924B (en) | 2022-02-21 | 2022-02-21 | Synthesis method of hydroxy pinacolone retinoic acid ester |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114436924B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115260071A (en) * | 2022-07-20 | 2022-11-01 | 湖州硕邦生物科技有限公司 | Preparation method of hydroxy pinacolone retinoic acid ester |
| CN116283697A (en) * | 2023-02-24 | 2023-06-23 | 英格尔检测技术服务（上海）有限公司 | Preparation method of hydroxy pinacolone retinoic acid ester |
| CN116396198B (en) * | 2023-03-29 | 2023-10-03 | 硕邦(湖州)生物医药科技有限公司 | Synthesis process of hydroxy pinacolone retinoic acid ester |
| WO2024199669A1 (en) | 2023-03-31 | 2024-10-03 | Symrise Ag | Preparations comprising hydroxy pinacolone retinoate |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4743400A (en) * | 1986-09-22 | 1988-05-10 | Mcneilab, Inc. | Process for preparing retinoyl chlorides |
| CN1130376A (en) * | 1993-07-20 | 1996-09-04 | 邻位药品公司 | Process for preparation of N-(4hydroxyphenyl)-retinamide |
| CN101139311A (en) * | 2007-09-11 | 2008-03-12 | 东南大学 | Method for mass preparation of formamide phenol compound |
| CN106631950A (en) * | 2016-09-23 | 2017-05-10 | 苏州药基美研医药科技有限公司 | Vitamin A compound and paeonol condensed derivatives and preparation method |
| CN110218168A (en) * | 2018-03-02 | 2019-09-10 | 上海现代药物制剂工程研究中心有限公司 | A kind of preparation method of the sodium salt of N- (alltrans-view Huang acyl group)-L- cysteic acid methyl ester |
| CN113149880A (en) * | 2021-04-24 | 2021-07-23 | 苏州铭开生物医药技术有限公司 | Preparation method of hydroxy pinacolone retinoic acid ester |
| US11072575B1 (en) * | 2020-09-19 | 2021-07-27 | Xi'an Taikomed Pharmaceutical Technology Co., Ltd. | Method of preparing a cinnamyl alcohol retinoic acid ester with antioxidant and antibacterial activities |
| CN113880797A (en) * | 2021-09-29 | 2022-01-04 | 南京先达医药科技有限公司 | Synthesis process of hydroxy pinacolone retinoic acid ester |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005020400A (en) * | 2003-06-26 | 2005-01-20 | Hitachi Communication Technologies Ltd | Radio base station, radio communication system, communication control method of radio base station, and construction method of radio communication network |
-
2022
- 2022-02-21 CN CN202210156402.5A patent/CN114436924B/en active Active
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4743400A (en) * | 1986-09-22 | 1988-05-10 | Mcneilab, Inc. | Process for preparing retinoyl chlorides |
| CN1130376A (en) * | 1993-07-20 | 1996-09-04 | 邻位药品公司 | Process for preparation of N-(4hydroxyphenyl)-retinamide |
| CN101139311A (en) * | 2007-09-11 | 2008-03-12 | 东南大学 | Method for mass preparation of formamide phenol compound |
| CN106631950A (en) * | 2016-09-23 | 2017-05-10 | 苏州药基美研医药科技有限公司 | Vitamin A compound and paeonol condensed derivatives and preparation method |
| CN110218168A (en) * | 2018-03-02 | 2019-09-10 | 上海现代药物制剂工程研究中心有限公司 | A kind of preparation method of the sodium salt of N- (alltrans-view Huang acyl group)-L- cysteic acid methyl ester |
| US11072575B1 (en) * | 2020-09-19 | 2021-07-27 | Xi'an Taikomed Pharmaceutical Technology Co., Ltd. | Method of preparing a cinnamyl alcohol retinoic acid ester with antioxidant and antibacterial activities |
| CN113149880A (en) * | 2021-04-24 | 2021-07-23 | 苏州铭开生物医药技术有限公司 | Preparation method of hydroxy pinacolone retinoic acid ester |
| CN113880797A (en) * | 2021-09-29 | 2022-01-04 | 南京先达医药科技有限公司 | Synthesis process of hydroxy pinacolone retinoic acid ester |
Non-Patent Citations (3)
| Title |
|---|
| Correlation of fluorescence quenching in carotenoporphyrin dyads with the energy of intramolecular charge transfer states. Effect of the number of conjugated double bonds of the carotenoid moiety;Fungo, Fernando 等;Physical Chemistry Chemical Physics;第5卷(第3期);469-475 * |
| 全反式维甲酸-正丁酸（丙戊酸） 前体药物的设计、合成及抗肿瘤活性研究;王欣 等;中国药物化学杂志;第18卷(第1期);1-5 * |
| 全反式维甲酸—正丁酸、丙戊酸相结合的化合物的设计、合成及抗肿瘤活性研究;王欣;沈阳药科大学硕士学位论文;全文 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN114436924A (en) | 2022-05-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN114436924B (en) | Synthesis method of hydroxy pinacolone retinoic acid ester | |
| CN106810426B (en) | Method for synthesizing cannabidiol | |
| CN102850248A (en) | Technology for preparing vitamin D3 | |
| CN108623507A (en) | The preparation method of Retinol Palmitate | |
| CN113861057A (en) | Oseltamivir phosphate intermediate impurity compound and preparation method and application thereof | |
| US11753389B2 (en) | Method for preparing dihydroquercetin | |
| CN114315535A (en) | Preparation method of eldecalcitol isomer impurity | |
| CN103044468A (en) | Preparation method of N-(2-pyrazine carbonyl)-L-phenylalanine-L- leucine boracic acid | |
| CA2497066C (en) | Process for the preparation of 13-cis-retinoic acid | |
| CN113354526B (en) | Alkali purification method of coenzyme Q10 | |
| AU2003217324A1 (en) | METHOD FOR PRODUCTION OF Beta-CRYPTOXANTHIN AND Alpha-CRYPTOXANTHIN FROM COMMERCIALLY AVAILABLE LUTEIN | |
| CN104418825A (en) | Method for purifying lipstatin | |
| CN113501752A (en) | Acid purification method of coenzyme Q10 | |
| CN113527064A (en) | Preparation method of phloroglucinol | |
| CN114853593A (en) | Method for extracting high-purity nervonic acid from acer truncatum buge oil | |
| CN114163411A (en) | Preparation method of enantiomer pure dihydromyricetin | |
| CN105732547A (en) | Preparation method of dehydrated andrographolide diacid half ester basic salt | |
| CN115677456B (en) | Preparation method of cannabidiol | |
| CN107235837B (en) | Preparation method of fenofibric acid | |
| CN1472183A (en) | Preparing method for high-purity lycopene | |
| CN111592553A (en) | Method for preparing moxidectin | |
| JP4397990B2 (en) | Purification method of 3-alkylflavanonol derivatives | |
| CN113045583A (en) | Preparation method of pinoxaden metabolite | |
| CN111187161B (en) | Preparation method of dihydrocapsaicin and dihydrocapsaicin ester | |
| CN105646530B (en) | Phenylpyrazole compound and preparation method and application thereof |
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 |