CN102584742A - Piperazine ferulate synthesis process - Google Patents
Piperazine ferulate synthesis process Download PDFInfo
- Publication number
- CN102584742A CN102584742A CN2011100055848A CN201110005584A CN102584742A CN 102584742 A CN102584742 A CN 102584742A CN 2011100055848 A CN2011100055848 A CN 2011100055848A CN 201110005584 A CN201110005584 A CN 201110005584A CN 102584742 A CN102584742 A CN 102584742A
- Authority
- CN
- China
- Prior art keywords
- piperazine
- piperazine ferulate
- less
- ferulate
- minutes
- 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
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a piperazine ferulate synthesis process. Ethanol of which the concentration is 50-95 percent is taken as a solvent; the mass ratio of the ethanol solvent to ferulic acid is not less than 4:1 but less than 8:1; the mass ratio of the ethanol solvent to anhydrous piperazidine is not less than 3:1 but less than 8:1; the crystalizing and salt-forming time of piperazine ferulate is more than 50 minutes but does not surpass 180 minutes; and the yield of the piperazine ferulate synthesized under the condition is more than 90 percent, and the content is not less than 99 percent. A small amount of ethanol solvent is used, the yield of the piperazine ferulate is high, a large amount of piperazine ferulate is synthesized at the same reaction volume, and the cost is saved greatly.
Description
Technical field
The present invention relates to a kind of synthesis technique of piperazine ferulate, the synthetic piperazine ferulate is mainly as medicinal use.
Background technology
Piperazine ferulate chemistry 3-methoxyl group by name-4-Hydroxycinnamic Acid piperazine, molecular formula is C
24H
30N
2O
8Piperazine ferulate also is the main active ingredient of Chinese medicine Ligusticum wallichii; Have anticoagulation, platelet aggregation-against, microcirculation improvement, releasing vasospasm and increase the effect of coronary flow, be applicable to clinically with assisting therapy such as the renal glomerulus ephrosis of microscopic hematuria and hypercoagulative state and coronary heart disease, cerebral infarction, vasculitiss.
Publication number be CN101555235A Invention Announce a kind of be solvent with ethanol; FLA and Piperazine anhydrous are the technology of the synthetic piperazine ferulate of starting raw material; Reactions step comprises dissolving, filtration, crystallization and whiz, it is characterized in that alcohol solvent concentration is 60% ~ 95%, and the mass ratio of alcohol solvent and FLA is 15:1 ~ 8:1; The mass ratio of alcohol solvent and Piperazine anhydrous is 15:1 ~ 8:1; The reaction mol ratio of FLA and Piperazine anhydrous is 4:1 ~ 2:1, and it is 10 minutes ~ 50 minutes that piperazine ferulate crystallizes into the reactant salt time, and the yield of piperazine ferulate is no more than 90%.
Summary of the invention
The objective of the invention is to improve the invention that publication number is CN101555235A, a kind of synthesis technique of piperazine ferulate, the consumption of minimizing alcohol solvent increases the reactant salt time that crystallizes into, and improves the yield of piperazine ferulate.The synthesis condition of the improved piperazine ferulate of the present invention comprises:
1, the mass ratio of alcohol solvent and FLA is less than 8:1, more than or equal to 4:1, is optimized for 7.5:1 ~ 6:1;
2, the mass ratio of alcohol solvent and Piperazine anhydrous more than or equal to 3:1, is optimized for 6:1 ~ 4:1 less than 8:1;
3, piperazine ferulate crystallization salt time is greater than 50 minutes, less than 180 minutes;
4, alcohol solvent concentration is 50% ~ 95% in the above-mentioned condition, is optimized for 65% ~ 85%.
All greater than 90%, its content is greater than 99% according to above-mentioned condition synthetic piperazine ferulate yield.The invention has the advantages that used alcohol solvent is few, the yield of piperazine ferulate is high, and same reaction volume synthetic piperazine ferulate is many, has greatly practiced thrift cost.Piperazine ferulate has a extensive future, and market capacity is big, under the suitability for industrialized production situation, with publication number be the invention ratio of CN101555235A, the present invention cost-saved 20% ~ 40%.
Embodiment
The present invention is on the basis of invention of CN101555235A at publication number, improve alcohol solvent and FLA ingredient proportion, alcohol solvent and Piperazine anhydrous ingredient proportion and piperazine ferulate crystallization salt time after, carried out series of studies, the result is following.
Embodiment 1
30 kilograms of FLA charging capacitys are dissolved in concentration and are in 200 liters of 70% ethanol; 7.5 kilograms of Piperazine anhydrous charging capacitys are dissolved in concentration and are in 37.5 liters of 70% ethanol; Both are filtered, slowly add the latter among the former, it is fully reacted, piperazine ferulate crystallization salt time is 90 minutes, through whiz, obtains 34.3 kilograms of piperazine ferulates, and yield is 91.5%, and content is 99.2%.
Embodiment 2
30 kilograms of FLA charging capacitys are dissolved in concentration and are in 190 liters of 70% ethanol; 7.5 kilograms of Piperazine anhydrous charging capacitys are dissolved in concentration and are in 37.5 liters of 70% ethanol; Both are filtered, slowly add the latter among the former, it is fully reacted, piperazine ferulate crystallization salt time is 120 minutes, through whiz, obtains 34.7 kilograms of piperazine ferulates, and yield is 92.5%, and content is 99.3%.
Embodiment 3
30 kilograms of FLA charging capacitys are dissolved in concentration and are in 180 liters of 70% ethanol; 7.5 kilograms of Piperazine anhydrous charging capacitys are dissolved in concentration and are in 37.5 liters of 70% ethanol; Both are filtered, slowly add the latter among the former, it is fully reacted, piperazine ferulate crystallization salt time is 150 minutes, through whiz, obtains 35.1 kilograms of piperazine ferulates, and yield is 93.6%, and content is 99.4%.
Claims (3)
1. piperazine ferulate synthesis technique, it is characterized in that comprising following some: the mass ratio of (1) alcohol solvent and FLA more than or equal to 4:1, is optimized for 7.5:1 ~ 6:1 for less than 8:1; (2) mass ratio of alcohol solvent and Piperazine anhydrous more than or equal to 3:1, is optimized for 6:1 ~ 4:1 less than 8:1; (3) piperazine ferulate crystallization salt time is greater than 50 minutes, less than 180 minutes.
2. according to the said piperazine ferulate synthesis technique of claim 1, it is characterized in that described alcohol solvent concentration is 50% ~ 95%, be optimized for 65% ~ 85%.
3. according to the said piperazine ferulate synthesis technique of claim 1, it is characterized in that according to above-mentioned condition synthetic piperazine ferulate yield greater than 90%, content is not less than 99%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011100055848A CN102584742A (en) | 2011-01-12 | 2011-01-12 | Piperazine ferulate synthesis process |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011100055848A CN102584742A (en) | 2011-01-12 | 2011-01-12 | Piperazine ferulate synthesis process |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102584742A true CN102584742A (en) | 2012-07-18 |
Family
ID=46474069
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011100055848A Pending CN102584742A (en) | 2011-01-12 | 2011-01-12 | Piperazine ferulate synthesis process |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102584742A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110540528A (en) * | 2019-08-26 | 2019-12-06 | 成都亨达药业有限公司 | novel piperazine ferulate crystal form I and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101555235A (en) * | 2009-05-20 | 2009-10-14 | 湖南康普制药有限公司 | Manufacture process of piperazine ferulate |
| US20090326259A1 (en) * | 2006-06-14 | 2009-12-31 | Tokyo University Of Marine Science And Technology | NF-Kappabeta Activation Inhibitor |
-
2011
- 2011-01-12 CN CN2011100055848A patent/CN102584742A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090326259A1 (en) * | 2006-06-14 | 2009-12-31 | Tokyo University Of Marine Science And Technology | NF-Kappabeta Activation Inhibitor |
| CN101555235A (en) * | 2009-05-20 | 2009-10-14 | 湖南康普制药有限公司 | Manufacture process of piperazine ferulate |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110540528A (en) * | 2019-08-26 | 2019-12-06 | 成都亨达药业有限公司 | novel piperazine ferulate crystal form I and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102731512B (en) | Preparation method of lurasidone intermediate and lurasidone | |
| CN101613341B (en) | Synthetic method of key intermediate of rosuvastatin calcium side chain | |
| US8153842B2 (en) | Method for producing 3-(2,2,2-trimethyl-hydrazinium) propionate dihydrate | |
| CN101624390B (en) | Preparation method of key intermediate of rosuvastatin calcium side chain | |
| CN109988132B (en) | Preparation method of amiodarone hydrochloride | |
| CN101434552A (en) | Method for splitting 4,5- dimethoxy-1-(methyl amino methyl)-benzocyclobutane | |
| CN102503805B (en) | Method for preparing 4-felbinac through rearrangement reaction | |
| CN103819475A (en) | Synthetic method of sitagliptin and salt thereof | |
| CN101979391B (en) | Method for preparing tiotropium bromide | |
| CN101824011A (en) | Method for preparing 3-O-alkyl ascorbic acid | |
| CN102702232A (en) | Method for preparation of fine cefamandole nafate | |
| CN101798280B (en) | Method for preparing S-(-)-amlodipine and R-(+)-amlodipine by chirally resolving racemic amlodipine | |
| CN103319487A (en) | Preparation method of sitagliptin and intermediate of sitagliptin | |
| CN102898418B (en) | Preparation method of esomeprazole magnesium | |
| CN102584742A (en) | Piperazine ferulate synthesis process | |
| JP7414814B2 (en) | (-)-New manufacturing process for cibenzoline succinate | |
| CN102363599B (en) | A kind of sitagliptin intermediate chiral separation method | |
| CN103145636A (en) | 1,4-diacyl-3,6-diphenyl-1,4-dihydrotetrazine compound as well as preparation method and application thereof | |
| CN102875397B (en) | Meclofenoxatum preparation method | |
| CN101514163B (en) | Optically pure Sibutramine and process for preparing salt derivative thereof | |
| CN102417482A (en) | Method for synthesizing ozagrel ethyl ester or ozagrel methyl ester | |
| CN103113408A (en) | Novel method for preparing fosfomycin phenylethylamine | |
| CN102977077A (en) | Method for preparing dabigatran etexilate intermediate | |
| CN103044361B (en) | Preparation method of (2R,3S)-epoxidation amino-benzene butane | |
| CN102424655B (en) | Preparation method of R-(-)-2-acetamido-3-methoxy-N-benzyl propionamide |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20120718 |