CN109456170B - Preparation method of calcium levulinate - Google Patents
Preparation method of calcium levulinate Download PDFInfo
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- CN109456170B CN109456170B CN201811443977.5A CN201811443977A CN109456170B CN 109456170 B CN109456170 B CN 109456170B CN 201811443977 A CN201811443977 A CN 201811443977A CN 109456170 B CN109456170 B CN 109456170B
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- 229940078480 calcium levulinate Drugs 0.000 title claims abstract description 31
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 title claims abstract description 31
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 claims abstract description 20
- 238000003756 stirring Methods 0.000 claims description 48
- 238000006243 chemical reaction Methods 0.000 claims description 45
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 32
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 24
- 238000010438 heat treatment Methods 0.000 claims description 24
- 239000013078 crystal Substances 0.000 claims description 17
- 238000001816 cooling Methods 0.000 claims description 16
- 238000001914 filtration Methods 0.000 claims description 16
- 239000011259 mixed solution Substances 0.000 claims description 16
- 239000000126 substance Substances 0.000 claims description 14
- 159000000007 calcium salts Chemical class 0.000 claims description 9
- 238000000746 purification Methods 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- 239000007864 aqueous solution Substances 0.000 claims description 8
- 238000002425 crystallisation Methods 0.000 claims description 8
- 230000008025 crystallization Effects 0.000 claims description 8
- 238000004821 distillation Methods 0.000 claims description 8
- 238000001035 drying Methods 0.000 claims description 8
- 239000000706 filtrate Substances 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 239000011541 reaction mixture Substances 0.000 claims description 8
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 8
- 239000007787 solid Substances 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- YCAWWWPXCXADIN-UHFFFAOYSA-L calcium 2-bromoacetate Chemical compound BrCC(=O)[O-].[Ca+2].BrCC(=O)[O-] YCAWWWPXCXADIN-UHFFFAOYSA-L 0.000 claims description 5
- OLBJZJZARFENTH-UHFFFAOYSA-L calcium;2-chloroacetate Chemical group [Ca+2].[O-]C(=O)CCl.[O-]C(=O)CCl OLBJZJZARFENTH-UHFFFAOYSA-L 0.000 claims description 5
- VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical class [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 claims description 3
- 238000000034 method Methods 0.000 abstract description 12
- 239000002994 raw material Substances 0.000 abstract description 6
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 abstract description 4
- 239000011575 calcium Substances 0.000 abstract description 4
- 229910052791 calcium Inorganic materials 0.000 abstract description 4
- -1 compound calcium salt Chemical class 0.000 abstract description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- XPFVYQJUAUNWIW-UHFFFAOYSA-N furfuryl alcohol Chemical compound OCC1=CC=CO1 XPFVYQJUAUNWIW-UHFFFAOYSA-N 0.000 description 6
- 238000004255 ion exchange chromatography Methods 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 239000000047 product Substances 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 3
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 208000013038 Hypocalcemia Diseases 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000705 hypocalcaemia Effects 0.000 description 2
- DSLZVSRJTYRBFB-LLEIAEIESA-N D-glucaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O DSLZVSRJTYRBFB-LLEIAEIESA-N 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 208000010496 Heart Arrest Diseases 0.000 description 1
- 208000002682 Hyperkalemia Diseases 0.000 description 1
- 206010020669 Hypermagnesaemia Diseases 0.000 description 1
- 206010027439 Metal poisoning Diseases 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 238000009098 adjuvant therapy Methods 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 201000005991 hyperphosphatemia Diseases 0.000 description 1
- 208000008127 lead poisoning Diseases 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/377—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups
- C07C51/38—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups by decarboxylation
Abstract
A preparation method of a calcium levulinate, and relates to a preparation method of a calcium levulinate. The method sequentially comprises the following steps: ethyl acetoacetate is used as a raw material, the ethyl acetoacetate reacts with calcium haloacetate under an alkaline condition to obtain corresponding compound calcium salt, and the compound calcium salt is hydrolyzed and decarboxylated under a strong alkaline condition to obtain the calcium levulinate.
Description
Technical Field
The invention relates to a preparation method of a calcium levulinate, and particularly relates to a method for preparing the calcium levulinate.
Background
Calcium levulinate, white crystals or powder, slightly bitter and astringent in taste, also known as: calcium gamma-pentanoate; calcium levulinate; calcium levo (saccharate); fructose calcium derivative; calcium levulinate; calcium levulinate (calcium levulinate); calcium levulinate is mainly used for treating acute hypocalcemia, chronic hypocalcemia, allergic diseases, lead poisoning, hyperphosphatemia and the like; also can be used for resuscitation of cardiac arrest, and adjuvant treatment of hypermagnesemia and hyperkalemia.
The medicine has mature market and large dosage, so that an appropriate synthetic route can directly determine the audience area and the application range of the medicine. At present, the domestic preparation methods of calcium levulinate mainly comprise two methods:
1, calcium levulinate is obtained by directly reacting calcium levulinate serving as a raw material with calcium carbonate, but the purity of a product obtained by the method is not high, and further purification is needed subsequently, so that the application of the method in the field of high purity is limited;
and 2, furfuryl alcohol is adopted as a raw material, and a corresponding calcium salt is obtained after hydrolysis rearrangement, so that the product obtained by the method is good in quality, but the final cost of the product is high due to the fact that the furfuryl alcohol is expensive in market price, and the method is not beneficial to market popularization.
Based on summarizing the relevant experience at home and abroad, a new route is provided, new cheap and easily available raw materials are adopted, the equipment is simple, and the operation is simple and convenient. On the premise of ensuring the quality, the production cost is effectively reduced.
Disclosure of Invention
The invention aims to provide a preparation method of calcium levulinate, which has the advantages of mild reaction conditions, simple process and equipment, convenient operation and no environmental pollution.
In order to achieve the purpose, a series of experiments are carried out, and a brand new synthetic route is provided.
The technical scheme for realizing the invention is as follows:
a preparation method of calcium levulinate is characterized by comprising the following steps: the calcium levulinate represented by formula (I) is obtained according to the following steps:
Ⅱ Ⅰ
preparation of calcium levulinate (I)
Adding 1 time of ethyl acetoacetate (II), 1.2 times of sodium ethoxide (molar ratio) and 5-10 times of ethanol (mass ratio) into a reactor, stirring uniformly, adding 0.5-0.55 times of calcium haloacetate in batches (molar ratio), heating to 60 ℃ after the addition is finished, continuing stirring for reaction for 4-6 hours, obtaining a mixed solution conforming to calcium salt after the reaction is finished, and directly using the mixed solution in the next step without purification. Wherein the halogenated calcium acetate is calcium chloroacetate or calcium bromoacetate.
Then distilling under reduced pressure to remove most of solvent ethanol, adding 6-12 times (mass ratio) of 10% sodium hydroxide aqueous solution into the mixture, uniformly stirring, heating to 30 ℃, continuously stirring for reaction for 5-8 hours, cooling to room temperature after the reaction is finished, adjusting the pH of the reaction mixture to 4 by using 5% dilute hydrochloric acid, heating to 60 ℃, stirring for reaction for 2 hours, generating gas overflow during the stirring reaction, reacting until no gas overflows, cooling to room temperature again, filtering to remove insoluble substances, removing most of water from the obtained filtrate through distillation, adding a small amount of seed crystals, standing for crystallization for 24 hours, filtering to collect precipitated solid, and drying in vacuum at 50 ℃ to obtain powdery crystal calcium levulinate.
The invention has the advantages that:
1. the new raw materials and the method adopted by the invention have the advantages of higher purity of the obtained product, effective control of the cost and convenience for market popularization of the product.
2. The raw materials in each step of the method are commercially available, the source is wide, the supply is sufficient, the reaction conditions are relatively mild, the process is simple, the reactions in each step are conventional operations and are easy to control, the pollution is reduced, the green production is realized, and the cost is effectively controlled, so that the industrial mass production of the method becomes possible.
Detailed Description
How this invention can be carried out is further illustrated by the following specific examples:
example 1
Adding ethyl acetoacetate (II) (130 g, 1.0 mol), sodium ethoxide (81.6 g, 1.2 mol) and ethanol (1300 g) into a reactor, stirring uniformly, adding calcium chloroacetate (124.8 g, about 0.55 mol) in batches, heating to 60 ℃ after the addition is finished, continuing stirring for reacting for 6 hours, obtaining a mixed solution conforming to calcium salt after the reaction is finished, and directly using the mixed solution in the next step without purification.
Then, distilling under reduced pressure to remove most of solvent ethanol, adding 10% sodium hydroxide aqueous solution (1550 g) into the mixture, uniformly stirring, heating to 30 ℃, continuing to stir for 8 hours, cooling to room temperature after the reaction is finished, adjusting the pH of the reaction mixture to 4 by using 5% diluted hydrochloric acid, heating to 60 ℃, stirring for reaction for 2 hours, generating gas during the stirring reaction, reacting until no gas overflows, cooling to room temperature again, filtering to remove insoluble substances, removing most of water from the obtained filtrate through distillation, adding a small amount of seed crystals, standing for crystallization for 24 hours, filtering to collect precipitated solid, and drying in vacuum at 50 ℃ to obtain 237.6g of powdery crystals which are calcium levulinate, wherein the yield is about 88.0%.
1H NMR (D2O,500MHz) δ:2.65-2.82(4H,m),2.15(3H,s)。
Melting point: the ion chromatography is matched with the standard substance at the temperature of between 124.6 and 125.2 ℃.
Example 2
Adding ethyl acetoacetate (II) (130 g, 1.0 mol), sodium ethoxide (81.6 g, 1.2 mol) and ethanol (650 g) into a reactor, stirring uniformly, adding calcium chloroacetate (113.5 g, 0.5 mol) in batches, heating to 60 ℃ after the addition is finished, continuing stirring for reaction for 4 hours, obtaining a mixed solution conforming to calcium salt after the reaction is finished, and directly using the mixed solution in the next step without purification.
Then, distilling under reduced pressure to remove most of solvent ethanol, adding 10% sodium hydroxide aqueous solution (800 g) into the mixture, uniformly stirring, heating to 30 ℃, continuing to stir for 5 hours, cooling to room temperature after the reaction is finished, adjusting the pH of the reaction mixture to 4 by using 5% diluted hydrochloric acid, heating to 60 ℃, stirring for reaction for 2 hours, generating gas during the stirring reaction, reacting until no gas overflows, cooling to room temperature again, filtering to remove insoluble substances, removing most of water from the obtained filtrate through distillation, adding a small amount of seed crystals, standing for crystallization for 24 hours, filtering to collect precipitated solid, and drying in vacuum at 50 ℃ to obtain 212.4g of powdery crystals which are calcium levulinate, wherein the yield is about 78.7%.
1H NMR (D2O,500MHz) δ:2.65-2.82(4H,m),2.15(3H,s)。
Melting point: the ion chromatography is matched with the standard substance at the temperature of between 124.6 and 125.2 ℃.
Example 3
Adding ethyl acetoacetate (II) (130 g, 1.0 mol), sodium ethoxide (81.6 g, 1.2 mol) and ethanol (1000 g) into a reactor, stirring uniformly, adding calcium chloroacetate (120.3 g, about 0.53 mol) in batches, heating to 60 ℃ after the addition is finished, continuing stirring for reaction for 5 hours, obtaining a mixed solution conforming to calcium salt after the reaction is finished, and directly using the mixed solution in the next step without purification.
Then, distilling under reduced pressure to remove most of solvent ethanol, adding 10% sodium hydroxide aqueous solution (1200 g) into the mixture, uniformly stirring, heating to 30 ℃, continuing to stir for reaction for 6 hours, cooling to room temperature after the reaction is finished, adjusting the pH of the reaction mixture to 4 by using 5% diluted hydrochloric acid, heating to 60 ℃, stirring for reaction for 2 hours, generating gas during the stirring reaction, reacting until no gas overflows, cooling to room temperature again, filtering to remove insoluble substances, removing most of water from the obtained filtrate through distillation, adding a small amount of seed crystals, standing for crystallization for 24 hours, filtering to collect precipitated solid, and drying in vacuum at 50 ℃ to obtain 226.3g of powdery crystals which are calcium levulinate, wherein the yield is about 83.8%.
1H NMR (D2O,500MHz) δ:2.65-2.82(4H,m),2.15(3H,s)。
Melting point: the ion chromatography is matched with the standard substance at the temperature of between 124.6 and 125.2 ℃.
Example 4
Adding ethyl acetoacetate (II) (130 g, 1.0 mol), sodium ethoxide (81.6 g, 1.2 mol) and ethanol (1300 g) into a reactor, stirring uniformly, adding calcium bromoacetate (173.8 g, 0.55 mol) in batches, heating to 60 ℃ after the addition is finished, continuing stirring for reacting for 6 hours, obtaining a mixed solution conforming to calcium salt after the reaction is finished, and directly using the mixed solution in the next step without purification.
Then, distilling under reduced pressure to remove most of solvent ethanol, adding 10% sodium hydroxide aqueous solution (1550 g) into the mixture, uniformly stirring, heating to 30 ℃, continuing to stir for 8 hours, cooling to room temperature after the reaction is finished, adjusting the pH of the reaction mixture to 4 by using 5% diluted hydrochloric acid, heating to 60 ℃, stirring for reaction for 2 hours, generating gas during the stirring reaction, reacting until no gas overflows, cooling to room temperature again, filtering to remove insoluble substances, removing most of water from the obtained filtrate through distillation, adding a small amount of seed crystals, standing for crystallization for 24 hours, filtering to collect precipitated solid, and drying in vacuum at 50 ℃ to obtain 230.5g of powdery crystals which are calcium levulinate, wherein the yield is about 85.4%.
1H NMR (D2O,500MHz) δ:2.65-2.82(4H,m),2.15(3H,s)。
Melting point: the ion chromatography is matched with the standard substance at the temperature of between 124.6 and 125.2 ℃.
Example 5
Adding ethyl acetoacetate (II) (130 g, 1.0 mol), sodium ethoxide (81.6 g, 1.2 mol) and ethanol (650 g) into a reactor, stirring uniformly, adding calcium bromoacetate (158 g, 0.5 mol) in batches, heating to 60 ℃ after the addition is finished, continuing stirring for reaction for 4 hours, obtaining a mixed solution conforming to calcium salt after the reaction is finished, and directly using the mixed solution in the next step without purification.
Then, distilling under reduced pressure to remove most of solvent ethanol, adding 10% sodium hydroxide aqueous solution (800 g) into the mixture, uniformly stirring, heating to 30 ℃, continuing to stir for 5 hours, cooling to room temperature after the reaction is finished, adjusting the pH of the reaction mixture to 4 by using 5% diluted hydrochloric acid, heating to 60 ℃, stirring for reaction for 2 hours, generating gas during the stirring reaction, reacting until no gas overflows, cooling to room temperature again, filtering to remove insoluble substances, removing most of water from the obtained filtrate through distillation, adding a small amount of seed crystals, standing for crystallization for 24 hours, filtering to collect precipitated solid, and drying in vacuum at 50 ℃ to obtain 202.9g of powdery crystals which are calcium levulinate, wherein the yield is about 75.1%.
1H NMR (D2O,500MHz) δ:2.65-2.82(4H,m),2.15(3H,s)。
Melting point: the ion chromatography is matched with the standard substance at the temperature of between 124.6 and 125.2 ℃.
Example 6
Adding ethyl acetoacetate (II) (130 g, 1.0 mol), sodium ethoxide (81.6 g, 1.2 mol) and ethanol (1000 g) into a reactor, stirring uniformly, adding calcium bromoacetate (167.5 g, about 0.53 mol) in batches, heating to 60 ℃ after the addition is finished, continuing stirring for reaction for 5 hours, and obtaining a mixed solution conforming to calcium salt after the reaction is finished, wherein the mixed solution can be directly used in the next step without purification.
Then, distilling under reduced pressure to remove most of solvent ethanol, adding 10% sodium hydroxide aqueous solution (1200 g) into the mixture, uniformly stirring, heating to 30 ℃, continuing to stir for reaction for 6 hours, cooling to room temperature after the reaction is finished, adjusting the pH of the reaction mixture to 4 by using 5% diluted hydrochloric acid, heating to 60 ℃, stirring for reaction for 2 hours, generating gas during the stirring reaction, reacting until no gas overflows, cooling to room temperature again, filtering to remove insoluble substances, removing most of water from the obtained filtrate through distillation, adding a small amount of seed crystals, standing for crystallization for 24 hours, filtering to collect precipitated solid, and drying in vacuum at 50 ℃ to obtain 218.3g of powdery crystals which are calcium levulinate, wherein the yield is about 80.9%.
1H NMR (D2O,500MHz) δ:2.65-2.82(4H,m),2.15(3H,s)。
Melting point: the ion chromatography is matched with the standard substance at the temperature of between 124.6 and 125.2 ℃.
Claims (1)
1. A preparation method of calcium levulinate is characterized by comprising the following steps: the calcium levulinate represented by formula (I) is obtained according to the following steps:
Ⅱ Ⅰ
preparation of calcium levulinate (I)
Adding ethanol with the molar ratio of ethyl acetoacetate (II) being 1 time, the molar ratio of sodium ethoxide being 1.2 times and the mass of ethyl acetoacetate being 5-10 times into a reactor, stirring uniformly, adding halogenated calcium acetate with the molar ratio being 0.5-0.55 times in batches, heating to 60 ℃ after the addition is finished, continuing stirring for reaction for 4-6 hours, obtaining a mixed solution conforming to calcium salt after the reaction is finished, and directly using the mixed solution in the next step without purification; wherein the halogenated calcium acetate is calcium chloroacetate or calcium bromoacetate;
then distilling under reduced pressure to remove most of solvent ethanol, adding 6-12 times of 10% sodium hydroxide aqueous solution by mass ratio into the mixture, uniformly stirring, heating to 30 ℃, continuing to stir for reaction for 5-8 hours, cooling to room temperature after the reaction is finished, adjusting the pH of the reaction mixture to 4 by using 5% dilute hydrochloric acid, heating to 60 ℃, stirring for reaction for 2 hours, generating gas overflow during the stirring reaction, reacting until no gas overflows, cooling to room temperature again, filtering to remove insoluble substances, removing most of water from the obtained filtrate through distillation, adding a small amount of seed crystals, standing for crystallization for 24 hours, filtering to collect precipitated solid, and drying in vacuum at 50 ℃ to obtain powdery crystal calcium levulinate.
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1304923A (en) * | 2000-12-04 | 2001-07-25 | 薛宝祺 | Preparing process and application of calcium levulinate |
CN103980108A (en) * | 2014-05-21 | 2014-08-13 | 华东理工大学 | Method for preparing 2-(1-methylalkyl) succinic acid |
WO2015134349A1 (en) * | 2014-03-03 | 2015-09-11 | Segetis, Inc. | Oxidation of solids bio-char from levulinic acid processes |
CN108358783A (en) * | 2018-04-13 | 2018-08-03 | 华烁科技股份有限公司 | The preparation method of 3- substituent glutaric acids diester and glutaconate diester |
-
2018
- 2018-11-29 CN CN201811443977.5A patent/CN109456170B/en active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1304923A (en) * | 2000-12-04 | 2001-07-25 | 薛宝祺 | Preparing process and application of calcium levulinate |
WO2015134349A1 (en) * | 2014-03-03 | 2015-09-11 | Segetis, Inc. | Oxidation of solids bio-char from levulinic acid processes |
CN103980108A (en) * | 2014-05-21 | 2014-08-13 | 华东理工大学 | Method for preparing 2-(1-methylalkyl) succinic acid |
CN108358783A (en) * | 2018-04-13 | 2018-08-03 | 华烁科技股份有限公司 | The preparation method of 3- substituent glutaric acids diester and glutaconate diester |
Non-Patent Citations (2)
Title |
---|
SYNTHESIS OF 3-ETHOXYCARBONYL-3-BUTEN-4-OLIDES AND 3-ETHOXYCARBONYL-4-BUTANOLIDES;GUADEMARBARDONE, F et al.;《SYNTHESIS》;19851231(第11期);第1043-1047页 * |
Synthesis of β-ethoxycarbonyl γ-lactones;Gaudemar-Bardone, F. et al.;《Tetrahedron Letters》;19841231;第25卷(第10期);第1047-1048页 * |
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