CN115043741A - Preparation method of full-alkyl substituted fumaric acid bisaminoalcohol ester and hydrochloride thereof - Google Patents
Preparation method of full-alkyl substituted fumaric acid bisaminoalcohol ester and hydrochloride thereof Download PDFInfo
- Publication number
- CN115043741A CN115043741A CN202210976601.0A CN202210976601A CN115043741A CN 115043741 A CN115043741 A CN 115043741A CN 202210976601 A CN202210976601 A CN 202210976601A CN 115043741 A CN115043741 A CN 115043741A
- Authority
- CN
- China
- Prior art keywords
- organic solvent
- solution
- hydrogen chloride
- chloride
- fumaric acid
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/06—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton from hydroxy amines by reactions involving the etherification or esterification of hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/08—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups
Abstract
The invention relates to the technical field of organic synthesis, in particular to a preparation method of full-alkyl substituted fumaric acid bisaminoalcohol ester and hydrochloride thereof; dissolving fumaroyl chloride in an aprotic solvent, adding a solution of hydrogen chloride in an organic solvent, and dropwise adding corresponding alkyl-substituted amino alcohol to obtain a compound of formula (I); dispersing the compound of formula (I) in an organic solvent, neutralizing with an aqueous solution of an inorganic base, and concentrating and extracting from the organic phase to obtain a compound of formula (II); the synthesis method of the invention is a special method for inhibiting the occurrence of side reactions by additionally adding a hydrogen chloride organic solvent solution in the esterification process, so that the target compound with high purity can be conveniently prepared by fumaric chloride. Compared with the disclosed method, the method has the advantages of simple steps, mild reaction conditions, no need of high-temperature reduced pressure distillation or high-temperature azeotropic dehydration, short production time, high product yield, good properties and the like.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a preparation method of full-alkyl substituted fumaric acid bisaminoalcohol ester and hydrochloride thereof.
Background
The full-alkyl substituted fumaric acid diamino alcohol ester and the corresponding salt thereof are compounds with a plurality of potential uses, can be used as plant growth regulators (disclosed by a patent CN 105906518B), can be further alkylated to prepare cationic surfactants (disclosed by a patent CN 101648119B), and can also be converted into other fine chemicals such as functionalized tartaric acid ester and the like through common simple chemical synthesis means.
At present, the following synthetic schemes exist mainly for the compounds of the class and the corresponding salts:
1. patent CN 101648119B discloses a synthesis method for preparing a target compound from dimethyl fumarate by ester exchange, the specific reaction formula is as follows:
the synthesis method needs to use metal sodium which is high in risk and not beneficial to production amplification, meanwhile, the product needs to be collected by reduced pressure distillation at 140-150 ℃, the process energy consumption is large, and the production efficiency is low.
2. In the synthesis method disclosed in patent CN 105906518B, bis (dimethylaminoethyl) fumarate is prepared by directly esterifying fumaric acid in the presence of a catalyst such as titanyl sulfate.
The synthesis method needs to carry out reflux water diversion at a high temperature of 110-150 ℃ for a long time, and meanwhile, the amino alcohol needs to be fed in an excessive amount and then is recovered through reduced pressure distillation, so that the production energy consumption is high, and the efficiency is low. Meanwhile, the intermediate needs to be decolorized by activated clay, so that a large amount of solid waste is generated.
3. Patent CN100402095C discloses a process for direct esterification or amidation via the corresponding acid chloride of fumaric acid in the presence of a base:
the synthesis method uses 4-dimethylamino pyridine and the like as catalysts and reacts in a solvent such as toluene and the like. However, the method has very low yield and dark reaction color, and needs additional decolorization treatment.
Disclosure of Invention
The purpose of the invention is: overcomes the defects in the prior art, and provides a preparation method of full-alkyl substituted fumaric acid bisaminoalcohol ester, which has short steps and good product properties and is suitable for industrial production
In order to achieve the purpose, the technical scheme adopted by the invention is as follows:
a process for the preparation of a salt of a perfluoroalkyl-substituted fumaric acid bis-amino alcohol, said process comprising the steps of:
dissolving fumaroyl chloride in an aprotic solvent, adding a solution of hydrogen chloride in an organic solvent, and dropwise adding corresponding alkyl-substituted amino alcohol to obtain a compound of formula (I);
wherein R1 is selected from one of simple alkyl groups such as methyl, ethyl, isopropyl and the like;
r2 is selected from linear or branched C2-C6 alkyl.
Further, the aprotic solvent is one or a mixture of tetrahydrofuran, 1, 4-dioxane, acetone, ethyl acetate, acetonitrile and dichloromethane, the hydrogen chloride is in a solution in an organic solvent, and the organic solvent is one selected from ethyl acetate, 1, 4-dioxane, diethyl ether and tetrahydrofuran.
Further, the aprotic solvent is acetonitrile, and the solution of hydrogen chloride in the organic solvent is a hydrogen chloride ethyl acetate solution.
Another object of the invention is: overcomes the defects in the prior art, and provides a preparation method of full-alkyl substituted fumaric acid diamino alcohol ester salt which has short steps and good product properties and is suitable for industrial production.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows:
a method for preparing a dialkyl substituted bisaminoester fumarate, the method comprising the steps of:
dissolving fumaroyl chloride in an aprotic solvent, adding a solution of hydrogen chloride in an organic solvent, and dropwise adding corresponding alkyl-substituted amino alcohol to obtain a compound shown in a formula (I);
and step two, dispersing the compound of the formula (I) prepared in the step one in an organic solvent, neutralizing with an aqueous solution of an inorganic base, and concentrating and extracting from an organic phase to obtain the compound of the formula (II).
Further, in the step one, the aprotic solvent is one or a mixture of several of tetrahydrofuran, 1, 4-dioxane, acetone, ethyl acetate, acetonitrile and dichloromethane, the hydrogen chloride is in a solution in an organic solvent, and the organic solvent is one of ethyl acetate, 1, 4-dioxane, diethyl ether and tetrahydrofuran.
Further, the aprotic solvent is acetonitrile, and the solution of hydrogen chloride in the organic solvent is a hydrogen chloride ethyl acetate solution.
Further, in the second step, the organic solvent is one or a mixture of more of ethyl acetate, isopropyl acetate, dichloromethane, 2-methyltetrahydrofuran and methyl tert-butyl ether, and the inorganic base is one or a mixture of more of sodium bicarbonate, sodium carbonate, potassium bicarbonate, potassium carbonate, sodium hydroxide and potassium hydroxide.
Further, the organic solvent in the second step is dichloromethane, and the inorganic base is sodium bicarbonate.
Further, the equivalent ratio of the alkyl-substituted amino alcohol to the fumaroyl chloride is 1.5:1 to 2.5: 1; a solution of hydrogen chloride in an organic solvent, wherein the equivalent ratio of hydrogen chloride to fumaryl chloride is 0.1:1 to 2.0: 1.
Further, the equivalent ratio of the alkyl-substituted amino alcohol to the fumaroyl chloride is 1.5:1 to 2.5: 1; a solution of hydrogen chloride in an organic solvent, wherein the equivalent ratio of hydrogen chloride to fumaryl chloride is 0.25:1 to 1.5: 1.
The technical scheme adopted by the invention has the beneficial effects that:
the synthesis method of the invention is a special method for inhibiting the occurrence of side reactions by additionally adding a hydrogen chloride organic solvent solution in the esterification process, so that the target compound with high purity can be conveniently prepared by fumaric chloride. Compared with the disclosed method, the method has the advantages of simple steps, mild reaction conditions, no need of high-temperature reduced pressure distillation or high-temperature azeotropic dehydration, short production time, high product yield, good properties and the like.
Detailed Description
The invention is further illustrated by the following examples, which are not intended to limit the scope of the invention. The experimental methods without specifying specific conditions in the following examples were selected according to the conventional methods and conditions, or according to the commercial instructions. If the temperature is not particularly emphasized, the reaction is usually carried out at room temperature, and the room temperature in the present invention is 10 to 30 ℃.
The experimental procedures used in the following examples are all conventional procedures unless otherwise specified.
Materials, reagents and the like used in the following examples are commercially available unless otherwise specified.
A method for preparing a dialkyl substituted bisaminoester fumarate, the method comprising the steps of:
dissolving fumaroyl chloride in an aprotic solvent, adding a solution of hydrogen chloride in an organic solvent, and dropwise adding corresponding alkyl-substituted amino alcohol to obtain a compound shown in a formula (I);
and step two, dispersing the compound of the formula (I) prepared in the step one in an organic solvent, neutralizing with an aqueous solution of an inorganic base, and concentrating and extracting from an organic phase to obtain the compound of the formula (II).
The compounds of the present invention, by their very nature and stability, are not suitable for preparation under conventional synthesis conditions. The method disclosed at present has the problems of harsh reaction conditions, high energy consumption, low production efficiency and more side reactions and dark color of the product. The invention creatively uses the conventional means, and adds the solution of hydrogen chloride in the direct esterification reaction of acyl chloride and alcohol which usually needs to additionally add alkali as an acid-binding agent, thereby preparing the product with high purity and better property under the mild condition of easy production and amplification. Wherein, the addition of the hydrogen chloride organic solvent solution effectively inhibits side reaction; and according to general chemical common knowledge, the addition of additional hydrogen chloride is not beneficial to complete conversion of the reaction, but in the method, the hydrogen chloride enables the product to be fully salified and separated out, but drives the reaction and improves the conversion rate. Therefore, the key technical improvement of the invention against the conventional and inventive method lies in the use of the hydrogen chloride organic solution. Secondly, the solvent acetonitrile preferred in the reaction and the hydrogen chloride ethyl acetate solution preferred in the organic solution of hydrogen chloride are the optimal conditions screened by a large number of comparative experiments by experimenters, are obviously superior to other solvent/reagent combinations in product quality, and are another key creation point in the invention.
Example 1: synthesis of fumaric acid bis (2- (dimethylaminoethyl)) ester dihydrochloride
Under the protection of nitrogen, the mixture is subjected toN,NDimethylethanolamine (2.21 g, 1.9 eq) was dissolved in dry acetonitrile to make a 10 mL solution ready for use. Under nitrogen protection, fumaric chloride (2.00 g, 1.0 eq) was separately dissolved in dry acetonitrile (30 mL) and cooled to 0. + -. 5 ℃. Subsequently adding dropwise the preparedN,N2.5 mL of a solution of dimethylethanolamine in acetonitrile. After completion of the dropwise addition, an ethyl acetate solution of hydrogen chloride (4M, 2.45 mL, 0.75 eq) was added to the reaction solution at once, followed by further dropwise addition of the restN,N7.5 mL of a solution of dimethylethanolamine in acetonitrile. After the dropwise addition, the reaction was carried out for 1 hour with stirring under heat preservation. Then, 30mL of absolute ethanol was added, and the mixture was filtered with stirring. The filter cake was slurried with 15 mL of cold absolute ethanol to remove unreacted starting materials, and finally filtered and dried to obtain the dihydrochloride of the target compound bis (2- (dimethylaminoethyl) fumarate as a white solid powder in a total of 3.85g, 89% yield. 1 H NMR (400 MHz, D 2 O) δ(ppm): 7.04 (s, 2H), 4.73 – 4.42 (m, 4H), 3.82 – 3.40 (m, 4H), 3.01 (s, 12H). 13 C NMR (101 MHz, D 2 O) δ(ppm): 165.5, 133.4, 59.5, 55.7, 43.1。
Example 2: synthesis of fumaric acid bis (2- (dimethylaminoethyl)) ester dihydrochloride
Under the protection of nitrogen, the mixture is subjected toN,NDimethylethanolamine (1.29 g, 2.2 eq) was dissolved in dry acetonitrile to make a 5 mL solution ready for use. Fumaric chloride (1.00 g, 1.0 eq) was separately dissolved in dry acetonitrile (12.5 mL) under nitrogen, cooled to 0 ± 5 ℃ and a solution of hydrogen chloride in ethyl acetate (4M, 2.5 mL, 1.5 eq) was added. Subsequently dropwise with maintenance of the temperatureN,N-a solution of dimethylethanolamine in acetonitrile. After the dropwise addition, the reaction was carried out for 0.5 h with stirring under heat preservation. Followed by filtration and drying to give the crude product as a white solid powder. The crude product is analyzed by NMR, and more than 10% of the crude product is presentN,N-hydrochloride salt of dimethylethanolamine. The crude product was washed by beating with 30mL of absolute ethanol at 0. + -. 5 ℃ for three times, followed by filtration and drying to give the dihydrochloride of the bis (2- (dimethylaminoethyl) fumarate, a target compound, as a white solid powder in a total of 1.82 g, in 84% yield.
Example 3: synthesis of fumaric acid bis (2- (dimethylaminoethyl)) ester dihydrochloride
Under the protection of nitrogen, the mixture is subjected toN,NDimethylethanolamine (1.06 g, 1.8 eq) was dissolved in dry acetonitrile to make 5 mL solution for use. Fumaric chloride (1.00 g, 1.0 eq) was separately dissolved in dry acetonitrile (12 mL) under nitrogen, cooled to 0 ± 5 ℃ and hydrogen chloride in ethyl acetate (4M, 0.4 mL, 0.25 eq) was added. Subsequently dropwise with maintenance of the temperatureN,N-a solution of dimethylethanolamine in acetonitrile. After the dropwise addition, the reaction was carried out for 0.5 h with stirring under heat preservation. Then, 15 mL of absolute ethanol was added, and the mixture was filtered with stirring. The filter cake was slurried with 8 mL of cold absolute ethanol to remove unreacted starting materials, and finally filtered and dried to obtain the dihydrochloride of the target compound bis (2- (dimethylaminoethyl) fumarate as an off-white solid powder in a total of 1.60 g, 74% yield.
Example 4: synthesis of fumaric acid bis (2- (dimethylaminoethyl)) ester dihydrochloride
Under the protection of nitrogen, the mixture is subjected toN,NDimethylethanolamine (2.21 g, 1.9 eq) was dissolved in dry tetrahydrofuran to make 10 mL solution for use. Under nitrogen, fumaric chloride (2.00 g, 1.0 eq) was separately dissolved in dry tetrahydrofuran (40 mL), cooled to 0 ± 5 ℃ and added with a solution of hydrogen chloride in ethyl acetate (4M, 2.45 mL, 0.75 eq). Then slowly dropwise adding while maintaining the temperatureN,NTetrahydrofuran solution of dimethylethanolamine, the reaction being more vigorous and withN,NThe addition of dimethylethanolamine gradually turns red in color. After the dropwise addition, the reaction was carried out for 0.5 h with stirring under heat preservation. Then, 30mL of absolute ethanol was added, and the mixture was filtered with stirring. The filter cake is beaten with 15 mL of cold absolute ethanol, 15 mL of dry acetonitrile and 15 mL of dry acetonitrile respectively, and finally filtered and dried to obtain the dihydrochloride of the target compound of fumaric acid bis (2- (dimethylaminoethyl)) ester, which is pink solid powder and has 3.01 g in total and the yield of 69%.
Example 5: synthesis of fumaric acid bis (3- (dimethylaminopropyl)) ester dihydrochloride
Under nitrogen protection, 3-dimethylamino-1-propanol (2.56 g, 1.9 eq) was dissolved in dry acetonitrile to make a 10 mL solution for use. Fumaric chloride (2.00 g, 1.0 eq) was separately dissolved in dry acetonitrile (30 mL) under nitrogen, and after cooling to 0 ± 5 ℃, a solution of hydrogen chloride in ethyl acetate (4M, 2.45 mL) was added thereto. Subsequently, the prepared acetonitrile solution of 3-dimethylamino-1-propanol was added dropwise to the reaction. After the dropwise addition, the reaction is carried out for 1 hour under the condition of heat preservation and stirring. Then, 30mL of absolute ethanol was added, and the mixture was filtered with stirring. The filter cake was slurried with 30mL of cold absolute ethanol to remove unreacted starting materials, and finally filtered and dried to obtain the dihydrochloride of the bis (3- (dimethylaminopropyl)) fumarate, a target compound, as a white solid powder in a total of 3.61 g, in 77% yield. 1 H NMR (400 MHz, D 2 O) δ(ppm): 6.98 (s, 2H), 4.39 (t, J = 6.0 Hz, 4H), 3.51 – 3.21 (m, 4H), 2.97 (s, 12H), 2.28-2.19 (m, 4H)。
Example 6: synthesis of bis (4- (dimethylaminobutyl)) fumarate dihydrochloride
Under the protection of nitrogen, 4-dimethylamino-1-butanol (2.91 g, 1.9 eq) was dissolved in dry acetonitrile to prepare a 10 mL solution for use. Fumaric chloride (2.00 g, 1.0 eq) was separately dissolved in dry acetonitrile (30 mL) under nitrogen, and after cooling to 0 ± 5 ℃, a solution of hydrogen chloride in ethyl acetate (4M, 2.45 mL) was added thereto. Subsequently, the prepared acetonitrile solution of 4-dimethylamino-1-butanol was added dropwise to the reaction. After the dropwise addition, the reaction is carried out for 0.5 h under the condition of heat preservation and stirring. Then, 100 mL of ethyl acetate was added, followed by stirring and filtration. The filter cake was slurried with 30mL of cold absolute ethanol and finally filtered and dried to obtain the dihydrochloride of the bis (4- (dimethylaminobutyl)) fumarate, a target compound, as a white-like solid powder in a total of 3.96 g with a yield of 78%.
Example 7: synthesis of bis (2- (dimethylaminoethyl)) fumarate
Bis (2- (dimethylaminoethyl) fumarate dihydrochloride (2.0 g) was dispersed in dichloromethane (40 mL) and aqueous sodium bicarbonate (1.52 g) (20 mL) under nitrogen, stirred well and then sodium chloride was added until saturated. Undissolved solids were removed by filtration, followed by separation and retention of the organic phase, washed with 8 mL of saturated brine. The organic phase was separated and concentrated to remove the solvent to give bis (2- (dimethylaminoethyl) fumarate as a yellowish oil in a total of 1.18 g, 76% yield. 1 H NMR (400 MHz, DMSO-d 6 ) δ(ppm): 6.75 (s, 2H), 4.24 (t, J = 5.7 Hz, 4H), 2.53 (t, J = 5.7 Hz, 4H, overlap with DMSO), 2.17 (s, 12H)。
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present invention should be subject to the appended claims.
Claims (10)
1. A preparation method of full-alkyl substituted fumaric acid diamino alcohol ester salt is characterized in that: the preparation method comprises the following steps:
dissolving fumaroyl chloride in an aprotic solvent, adding a solution of hydrogen chloride in an organic solvent, and dropwise adding corresponding alkyl-substituted amino alcohol to obtain a compound of formula (I);
wherein R1 is selected from one of methyl, ethyl and isopropyl;
r2 is selected from linear or branched C2-C6 alkyl.
2. The process for preparing a dialkyl fumarate of claim 1, wherein: the aprotic solvent is one or a mixture of tetrahydrofuran, 1, 4-dioxane, acetone, ethyl acetate, acetonitrile and dichloromethane, the hydrogen chloride is a solution in an organic solvent, and the organic solvent is one selected from ethyl acetate, 1, 4-dioxane, diethyl ether and tetrahydrofuran.
3. The process for preparing a dialkyl fumarate of claim 2, wherein: the aprotic solvent is acetonitrile, and the solution of hydrogen chloride in the organic solvent is a hydrogen chloride ethyl acetate solution.
4. A preparation method of full-alkyl substituted fumaric acid bisaminoalcohol ester is characterized in that: the preparation method comprises the following steps:
dissolving fumaroyl chloride in an aprotic solvent, adding a solution of hydrogen chloride in an organic solvent, and dropwise adding corresponding alkyl-substituted amino alcohol to obtain a compound shown in a formula (I);
and step two, dispersing the compound of the formula (I) prepared in the step one in an organic solvent, neutralizing with an aqueous solution of an inorganic base, and concentrating and extracting from an organic phase to obtain the compound of the formula (II).
5. The method for preparing the dialkyl substituted fumaric acid bisaminoalcohol ester according to claim 4, wherein: in the step one, the aprotic solvent is one or a mixture of tetrahydrofuran, 1, 4-dioxane, acetone, ethyl acetate, acetonitrile and dichloromethane, the hydrogen chloride is in a solution in an organic solvent, and the organic solvent is one selected from ethyl acetate, 1, 4-dioxane, diethyl ether and tetrahydrofuran.
6. The method for preparing the dialkyl substituted fumaric acid bisamino ester according to claim 5, wherein: the aprotic solvent is acetonitrile, and the solution of hydrogen chloride in the organic solvent is a hydrogen chloride ethyl acetate solution.
7. The method for preparing the dialkyl substituted fumaric acid bisaminoalcohol ester according to claim 4, wherein: in the second step, the organic solvent is one or a mixture of ethyl acetate, isopropyl acetate, dichloromethane, 2-methyltetrahydrofuran and methyl tert-butyl ether, and the inorganic base is one or a mixture of sodium bicarbonate, sodium carbonate, potassium bicarbonate, potassium carbonate, sodium hydroxide and potassium hydroxide.
8. The method for preparing the dialkyl substituted fumaric acid bisamino ester according to claim 7, wherein: and in the second step, the organic solvent is dichloromethane, and the inorganic base is sodium bicarbonate.
9. The method for preparing the dialkyl substituted fumaric acid bisaminoalcohol ester according to claim 4, wherein: the equivalent ratio of the alkyl-substituted amino alcohol to the fumaryl chloride is 1.5: 1-2.5: 1; a solution of hydrogen chloride in an organic solvent, wherein the equivalent ratio of hydrogen chloride to fumaryl chloride is 0.1:1 to 2.0: 1.
10. The method for preparing the dialkyl substituted fumaric acid bisamino ester according to claim 9, wherein: the equivalent ratio of the alkyl-substituted amino alcohol to the fumaryl chloride is 1.5: 1-2.5: 1; a solution of hydrogen chloride in an organic solvent, wherein the equivalent ratio of hydrogen chloride to fumaryl chloride is 0.25:1 to 1.5: 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210976601.0A CN115043741A (en) | 2022-08-15 | 2022-08-15 | Preparation method of full-alkyl substituted fumaric acid bisaminoalcohol ester and hydrochloride thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210976601.0A CN115043741A (en) | 2022-08-15 | 2022-08-15 | Preparation method of full-alkyl substituted fumaric acid bisaminoalcohol ester and hydrochloride thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115043741A true CN115043741A (en) | 2022-09-13 |
Family
ID=83166460
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210976601.0A Pending CN115043741A (en) | 2022-08-15 | 2022-08-15 | Preparation method of full-alkyl substituted fumaric acid bisaminoalcohol ester and hydrochloride thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115043741A (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1845758A (en) * | 2003-09-02 | 2006-10-11 | 吉万奥丹股份有限公司 | Aminoalkyl substituted esters and amides of fumaric acid for neutralising malodor |
| CN101648119A (en) * | 2009-09-11 | 2010-02-17 | 蚌埠丰原医药科技发展有限公司 | Cation Gemini surfactant and preparation method thereof |
| CN103145565A (en) * | 2013-03-15 | 2013-06-12 | 河南工业大学 | Preparation method of diester plasticizer containing tertiary amino |
| US20140275048A1 (en) * | 2013-03-14 | 2014-09-18 | Alkermes Pharma Ireland Limited | Prodrugs of fumarates and their use in treating various diseases |
| CN105906518A (en) * | 2016-05-24 | 2016-08-31 | 苏州科技学院 | Plant growth regulator fumaric bisdiethylamino ethanol ester citrate compound and preparation method thereof |
-
2022
- 2022-08-15 CN CN202210976601.0A patent/CN115043741A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1845758A (en) * | 2003-09-02 | 2006-10-11 | 吉万奥丹股份有限公司 | Aminoalkyl substituted esters and amides of fumaric acid for neutralising malodor |
| CN101648119A (en) * | 2009-09-11 | 2010-02-17 | 蚌埠丰原医药科技发展有限公司 | Cation Gemini surfactant and preparation method thereof |
| US20140275048A1 (en) * | 2013-03-14 | 2014-09-18 | Alkermes Pharma Ireland Limited | Prodrugs of fumarates and their use in treating various diseases |
| CN103145565A (en) * | 2013-03-15 | 2013-06-12 | 河南工业大学 | Preparation method of diester plasticizer containing tertiary amino |
| CN105906518A (en) * | 2016-05-24 | 2016-08-31 | 苏州科技学院 | Plant growth regulator fumaric bisdiethylamino ethanol ester citrate compound and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR20130129180A (en) | Process for preparing aminobenzoylbenzofuran derivatives | |
| CN101367760A (en) | Synthesis of 2-chlorine apellagrin | |
| CN108864050B (en) | Method for synthesizing Arotinib and hydrochloride thereof | |
| CN104591959B (en) | A kind of preparation method of diphenylethylene compounds | |
| KR101595747B1 (en) | Method for preparing of nafamostat mesilate | |
| CN115043741A (en) | Preparation method of full-alkyl substituted fumaric acid bisaminoalcohol ester and hydrochloride thereof | |
| JP2021536481A (en) | How to prepare lenvatinib | |
| JP4284423B2 (en) | Method for producing styrene derivative | |
| CN110818619B (en) | Synthetic method of N- (3-chloro-4- (2-pyridylmethoxy) phenyl) -2-cyanoacetamide | |
| CN111233745B (en) | (E)1- (9-alkyl-carbazole-3-) -acrylic acid and preparation method thereof | |
| CN109796360B (en) | Preparation process of 3-amino-2-naphthoic acid compound | |
| BG63116B1 (en) | Method for the preparation of 0-(3-amino-2-hydroxy-propyl)-hydroxime acylhalogenides | |
| EP1222179A4 (en) | Process for preparing piperazine-substituted aliphatic carboxylates | |
| US4450274A (en) | Preparation of ethambutol-diisoniazide methane sulfonic acid salt | |
| CN106008357A (en) | Novel impurity of telmisartan and synthesis method thereof | |
| CN110845371A (en) | Method for synthesizing o-sulfobenzaldehyde under normal pressure | |
| CN109851542A (en) | One kind (S)-N- methyl-N- (pyrrolidin-3-yl) acetamid dihydrochloride and its synthetic method | |
| CN112225736B (en) | Preparation method of 6-bromoimidazo [1.2-a ] pyridine-3-formaldehyde | |
| CN111592451B (en) | Preparation method of 4- (4-phenylbutoxy) benzoic acid | |
| JPS61233658A (en) | Novel cyclopropane derivative | |
| CN111004141B (en) | New method for synthesizing nintedanib intermediate 2-chloro-N-methyl-N- (4-nitrophenyl) acetamide | |
| CN108383781B (en) | Synthesis method of 6-hydroxy-3, 4-dihydro-2 (1H) -quinolinone | |
| CN117534613A (en) | Preparation method of 3-aminopyridine-2-carboxylic acid methyl ester | |
| US4434104A (en) | Preparation of high purity di-lower alkyl naphthalenedisulfonates | |
| US2782231A (en) | Preparation of malonanilic acid and substituted malonanilic acids |
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 |