CN1651417A - Preparation method of acymose - Google Patents
Preparation method of acymose Download PDFInfo
- Publication number
- CN1651417A CN1651417A CN 200410098726 CN200410098726A CN1651417A CN 1651417 A CN1651417 A CN 1651417A CN 200410098726 CN200410098726 CN 200410098726 CN 200410098726 A CN200410098726 A CN 200410098726A CN 1651417 A CN1651417 A CN 1651417A
- Authority
- CN
- China
- Prior art keywords
- reaction
- hours
- intermediate compound
- extraction
- acipimox
- 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.)
- Granted
Links
- 238000002360 preparation method Methods 0.000 title claims description 11
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims abstract description 14
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000012286 potassium permanganate Substances 0.000 claims abstract description 5
- 238000006243 chemical reaction Methods 0.000 claims description 23
- DJQOOSBJCLSSEY-UHFFFAOYSA-N Acipimox Chemical compound CC1=CN=C(C(O)=O)C=[N+]1[O-] DJQOOSBJCLSSEY-UHFFFAOYSA-N 0.000 claims description 18
- 229960003526 acipimox Drugs 0.000 claims description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 10
- 239000002904 solvent Substances 0.000 claims description 10
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 claims description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 9
- 238000003756 stirring Methods 0.000 claims description 8
- 238000000605 extraction Methods 0.000 claims description 7
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 229960000583 acetic acid Drugs 0.000 claims description 5
- 239000012362 glacial acetic acid Substances 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 4
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 4
- 239000012043 crude product Substances 0.000 claims description 4
- 238000003810 ethyl acetate extraction Methods 0.000 claims description 4
- 239000001632 sodium acetate Substances 0.000 claims description 4
- 235000017281 sodium acetate Nutrition 0.000 claims description 4
- XMVONEAAOPAGAO-UHFFFAOYSA-N sodium tungstate Chemical compound [Na+].[Na+].[O-][W]([O-])(=O)=O XMVONEAAOPAGAO-UHFFFAOYSA-N 0.000 claims description 4
- 238000000967 suction filtration Methods 0.000 claims description 4
- 229960001701 chloroform Drugs 0.000 claims description 3
- 238000001816 cooling Methods 0.000 claims description 3
- 239000000706 filtrate Substances 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- 238000001953 recrystallisation Methods 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 2
- 230000001105 regulatory effect Effects 0.000 claims description 2
- 238000000638 solvent extraction Methods 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 7
- LCZUOKDVTBMCMX-UHFFFAOYSA-N 2,5-Dimethylpyrazine Chemical compound CC1=CN=C(C)C=N1 LCZUOKDVTBMCMX-UHFFFAOYSA-N 0.000 abstract description 6
- 239000001934 2,5-dimethylpyrazine Substances 0.000 abstract description 3
- 230000001590 oxidative effect Effects 0.000 abstract 2
- 230000003301 hydrolyzing effect Effects 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 9
- 238000007254 oxidation reaction Methods 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 3
- PVNIIMVLHYAWGP-UHFFFAOYSA-N nicotinic acid Natural products OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 3
- -1 5-methylpyrazine-2-carboxylic acid-4-oxide compound Chemical class 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 108010010234 HDL Lipoproteins Proteins 0.000 description 2
- 102000015779 HDL Lipoproteins Human genes 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000007810 chemical reaction solvent Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 229960003512 nicotinic acid Drugs 0.000 description 2
- 235000001968 nicotinic acid Nutrition 0.000 description 2
- 239000011664 nicotinic acid Substances 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 108010007622 LDL Lipoproteins Proteins 0.000 description 1
- 102000007330 LDL Lipoproteins Human genes 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000021588 free fatty acids Nutrition 0.000 description 1
- 230000000055 hyoplipidemic effect Effects 0.000 description 1
- 208000006575 hypertriglyceridemia Diseases 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 125000000627 niacin group Chemical group 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 238000011020 pilot scale process Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
A process for preparing Aximosi from 2,5-dimethyl pyrazine includes such steps as oxidizing by H2O2, esterifying by acetic acid anhydride, hydrolyzing in alkaline condition, and oxidizing by potassium permanganate and H2O2.
Description
Technical field
The present invention relates to the preparation method of compound acipimox (5-methylpyrazine-2-carboxylic acid-4-oxide compound).
Background technology
Acipimox (Acipimox) is the common name of 5-methylpyrazine-2-carboxylic acid-4-oxide compound, and its structural formula is:
Acipimox is a nicotinic acid derivates, is used for the treatment of hypertriglyceridemia and hypercholesterolemia, and its steatolysis restraining effect activity is 20 times of nicotinic acid.It can suppress fatty tissue and discharge free fatty acids, reduce the blood level of vldl and low-density lipoprotein, cause the reduction of triglyceride level and total cholesterol level in the blood, simultaneously high-density lipoprotein (HDL)---cholesterol amount can be improved, the content of lipid in the blood can be improved within one month taking medicine usually.Therefore, acipimox is a kind of hypolipidemic that market outlook are arranged very much.
J.Org.Chem.26 discloses the preparation method of acipimox in 126 (1961), and with 2, the 5-dimethylpyrazine is a starting raw material, through H
2O
2Oxidation has prepared intermediate compound I, becomes ester through the diacetyl oxide esterification then, has prepared intermediate II, after hydrolysis has prepared intermediate III through NaOH, prepared intermediate compound IV with potassium permanganate oxidation then, at last again through H
2O
2Oxidation obtains acipimox.Through the reaction of five steps, the total recovery of acipimox crude product is about 10% altogether for this reaction scheme.Because the total recovery of this reaction scheme is too low, production cost is too high, is difficult to realize suitability for industrialized production.
Summary of the invention
Purpose of the present invention on the basis of existing technology, improve the deficiencies in the prior art, grope by a large amount of experiments, appropriate catalyst, reaction solvent and processing condition have been selected for use, optimized reaction conditions, provide a kind of stable operation, quality controllable, yield is higher and the preparation method of lower-cost acipimox.
The technical solution adopted in the present invention comprises the steps:
A. in reactor, drop into 2, the 5-dimethylpyrazine, hydrogen peroxide, glacial acetic acid, the ratio of three's amount of substance is 1: 2: 5～10, and temperature of reaction is 70～80 ℃, and the reaction times is 10～14 hours.Remove acetate after reacting completely under reduced pressure, add adjusting PH with base＞10, use organic solvent extraction, dry back is steamed and is desolventized, and residue obtains intermediate compound I with benzene or toluene recrystallization.Used extraction solvent is a methylene dichloride, trichloromethane, 1,2-ethylene dichloride.
B. drop into glacial acetic acid, diacetyl oxide, sodium acetate and intermediate compound I in reactor, back flow reaction 4～7 hours removes solvent under reduced pressure, and the cut of collecting 120 ℃/12mmHg is an intermediate II.Wherein acetate is solvent, and sodium acetate is a catalyzer, makes yield than J.Org.Chem.26, the raising in 126 (1961) nearly 50%.
C. intermediate II is put in 10% the sodium hydroxide solution, ethyl acetate extraction use in stirring at room reaction 24 hours, dry back concentrated intermediate III.In this reactions steps, J.Org.Chem.26, reaction conditions in 126 (1961) is reaction 96h, adopt ether extraction, and the applicant is being surprisingly found out that in fact this reaction does not need so long hydrolysis time, and finds to adopt ethyl acetate extraction to have unforeseeable high yield.
D. intermediate III is soluble in water, splash into potassium permanganate solution under stirring, react after 1 hour, add hydrochloric acid the solution purple is disappeared, filter the rear filtrate butanone extraction, remove solvent after the drying under reduced pressure and obtain intermediate compound IV.
E. input sodium wolframate and 30% hydrogen peroxide in water are regulated pH=1.5, add intermediate compound IV, 70 ℃ of reactions 14～16 hours, and cooling, suction filtration gets the acipimox crude product after the oven dry.Wherein sodium wolframate is a catalyzer.The applicant also finds to adopt above-mentioned condition to have extraordinary selectivity and higher yield for the nitrogen-atoms on the oxidation pyrazine ring in synthetic acipimox process.
Above-mentioned reaction scheme is:
2,5-dimethylpyrazine intermediate compound I intermediate II
Intermediate III intermediate compound IV acipimox
In the acipimox building-up process, we are mainly around how improving processing condition to improve product yield, we are to the feed ratio of reaction, temperature of reaction, and reaction times and terminal point are controlled, the selection of reaction solvent, by constantly groping, each step process has all been done to study in great detail, optimize and select, processing condition are gradually improved, and yield is improved.Whole production technology after the improvement, stable operation, yield is higher, and production cost has also had decline significantly, and through the pilot scale checking, big production test-manufactured, and can be fit to big production requirement fully.
Embodiment
The invention will be further elaborated below by embodiment.
Embodiment 1: the preparation of intermediate compound I
2,5-dimethylpyrazine 200g (1.85mol) and 200ml30% hydrogen peroxide, 900ml acetate remove solvent under reduced pressure 70 ℃ of stirring reactions 12 hours, add the 500ml frozen water in the residuum, transfer pH＞10 with 20% sodium hydroxide solution, use chloroform extraction, dry back is steamed and is desolventized residuum toluene recrystallization, suction filtration, after the drying white solid 177g, yield 77%, m.p.105～107 ℃.
Embodiment 2: the preparation of intermediate II
Diacetyl oxide 270ml, sodium acetate 78g and glacial acetic acid 1750ml are joined in the reactor, stir after 10 minutes, if intermediate compound I 133g (1.07mol), after the back flow reaction 5 hours, remove solvent earlier under reduced pressure, collect cut then, obtain the 151g intermediate II, yield is 85%, b.p.120～123 ℃/12mmHg.
Embodiment 3: the preparation of intermediate III
With the sodium hydroxide solution of intermediate II 64g (0.38mol) and 300ml 10% stirring reaction 24 hours at room temperature, use ethyl acetate extraction, anhydrous MgSO
4After the drying, concentrate intermediate III 39g, yield is 83%, m.p.34～36 ℃.
Embodiment 4: the preparation of intermediate compound IV
Intermediate III 12.5g (0.10mol) is dissolved in the 160ml water, under fully stirring, drips potassium permanganate solution [KmnO
420g (0.13mol), H
2O280ml], react after 1 hour, add hydrochloric acid the solution purple is disappeared, filter the rear filtrate butanone extraction, remove solvent after the drying under reduced pressure and obtain intermediate compound IV 11g, yield is 80%, m.p.163～167 ℃.
Embodiment 5: the preparation of acipimox
At the sodium wolframate aqueous solution (Na
2WO
42H
2O 1g, H
2O 50ml) adds 30% hydrogen peroxide 12ml in, behind dilute sulphuric acid accent pH to 1.5, add 20g intermediate compound IV (0.14mol), reacted 3 hours down at 70 ℃, the reaction solution cooling, suction filtration, drying, after the oven dry acipimox crude product 19.5g, yield is 90%, m.p.182～184 ℃.
Claims (2)
1. the preparation method of an acipimox is characterized in that this method may further comprise the steps:
A. in reactor, drop into 2, the 5-dimethylpyrazine, hydrogen peroxide, glacial acetic acid, the ratio of three's amount of substance is 1: 2: 5～10, temperature of reaction is 70～80 ℃, and the reaction times is 10～14 hours, removes acetate under reduced pressure after reacting completely, add adjusting PH with base＞10, use organic solvent extraction, dry back is steamed and is desolventized, and residue obtains intermediate compound I with benzene or toluene recrystallization;
B. drop into glacial acetic acid, diacetyl oxide, sodium acetate and intermediate compound I in reactor, back flow reaction 4～7 hours removes solvent under reduced pressure, and the cut of collecting 120 ℃/12mmHg is an intermediate II;
C. intermediate II is put in 10% the sodium hydroxide solution, ethyl acetate extraction use in stirring at room reaction 24 hours, dry back concentrated intermediate III;
D. intermediate III is soluble in water, splash into potassium permanganate solution under stirring, react after 1 hour, add hydrochloric acid the solution purple is disappeared, filter the rear filtrate butanone extraction, remove solvent after the drying under reduced pressure and obtain intermediate compound IV;
E. input sodium wolframate and 30% hydrogen peroxide in water are regulated pH=1.5, add intermediate compound IV, 70 ℃ of reactions 14～16 hours, and cooling, suction filtration gets the acipimox crude product after the oven dry.
2. method according to claim 1 is characterized in that the used extraction solvent of step a is methylene dichloride, trichloromethane or 1, the 2-ethylene dichloride.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410098726 CN1282647C (en) | 2004-12-15 | 2004-12-15 | Preparation method of acymose |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410098726 CN1282647C (en) | 2004-12-15 | 2004-12-15 | Preparation method of acymose |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1651417A true CN1651417A (en) | 2005-08-10 |
| CN1282647C CN1282647C (en) | 2006-11-01 |
Family
ID=34869525
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410098726 Expired - Fee Related CN1282647C (en) | 2004-12-15 | 2004-12-15 | Preparation method of acymose |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1282647C (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101434609B (en) * | 2008-12-19 | 2011-03-30 | 齐鲁天和惠世制药有限公司 | Catalytic oxidation system and use thereof in tazobactam synthesis |
| CN101899012B (en) * | 2009-05-30 | 2012-05-30 | 鲁南制药集团股份有限公司 | Method for improving synthesis process of Acipimox |
| CN103664805A (en) * | 2013-12-05 | 2014-03-26 | 华北水利水电大学 | Method for preparing acipimox |
| CN103923024A (en) * | 2014-04-25 | 2014-07-16 | 山东新时代药业有限公司 | Refining method of acipimox |
| CN105218464A (en) * | 2014-05-26 | 2016-01-06 | 四川亿明药业股份有限公司 | The synthesis technique of acipimox |
| CN108017586A (en) * | 2018-01-26 | 2018-05-11 | 常州工程职业技术学院 | A kind of preparation method of 5-Methylpyrazine-2-carboxylic acid |
| CN112125857A (en) * | 2019-06-25 | 2020-12-25 | 鲁南制药集团股份有限公司 | Preparation method of acipimox |
-
2004
- 2004-12-15 CN CN 200410098726 patent/CN1282647C/en not_active Expired - Fee Related
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101434609B (en) * | 2008-12-19 | 2011-03-30 | 齐鲁天和惠世制药有限公司 | Catalytic oxidation system and use thereof in tazobactam synthesis |
| CN101899012B (en) * | 2009-05-30 | 2012-05-30 | 鲁南制药集团股份有限公司 | Method for improving synthesis process of Acipimox |
| CN103664805A (en) * | 2013-12-05 | 2014-03-26 | 华北水利水电大学 | Method for preparing acipimox |
| CN103664805B (en) * | 2013-12-05 | 2016-05-11 | 华北水利水电大学 | A kind of method of preparing Acipimox |
| CN103923024A (en) * | 2014-04-25 | 2014-07-16 | 山东新时代药业有限公司 | Refining method of acipimox |
| CN105218464A (en) * | 2014-05-26 | 2016-01-06 | 四川亿明药业股份有限公司 | The synthesis technique of acipimox |
| CN105218464B (en) * | 2014-05-26 | 2018-04-06 | 四川亿明药业股份有限公司 | The synthesis technique of Acipimox |
| CN108017586A (en) * | 2018-01-26 | 2018-05-11 | 常州工程职业技术学院 | A kind of preparation method of 5-Methylpyrazine-2-carboxylic acid |
| CN108017586B (en) * | 2018-01-26 | 2021-04-23 | 常州工程职业技术学院 | Preparation method of 5-methylpyrazine-2-carboxylic acid |
| CN112125857A (en) * | 2019-06-25 | 2020-12-25 | 鲁南制药集团股份有限公司 | Preparation method of acipimox |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1282647C (en) | 2006-11-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109762043B (en) | Chenodeoxycholic acid and preparation method thereof | |
| CN105777835B (en) | Method for preparing chenodeoxycholic acid analogue | |
| CN101987860B (en) | Preparation method of ursodesoxycholic acid | |
| CN1282647C (en) | Preparation method of acymose | |
| CN109929896B (en) | Production process of ursodeoxycholic acid | |
| CN107602651A (en) | A kind of preparation method of dehydroepiandros-sterone intermediate and dehydroepiandros-sterone | |
| CN113493814B (en) | Dehydroepiandrosterone biosynthesis method | |
| CN109734656B (en) | Preparation method of nitrendipine | |
| CN103665078B (en) | A kind of preparation method of 17 Alpha-hydroxy steroidal esters | |
| WO2006128952A1 (en) | Process for the preparation of adamantane derivatives | |
| CN105481926A (en) | Method for directly preparing chenodeoxycholic acid from duck bile | |
| CN113461764A (en) | Synthetic method of ursodeoxycholic acid | |
| CN114315948A (en) | Method for extracting hyodeoxycholic acid from pig bile paste | |
| CN1101401C (en) | Stereo-selective synthesizing method for ursodesoxycholic acid | |
| CA1150239A (en) | Process for preparing high purity ursodeoxycholic acid | |
| CN110003302B (en) | Refining method of 7-ketolithocholic acid | |
| FR2464961A1 (en) | PROCESS FOR THE PREPARATION OF L-A-GLYCERYLPHOSPHORYL CHOLINE | |
| JP4393640B2 (en) | Production of plant sterols | |
| CN1061985C (en) | Method for preparation of progestol by degradation of steroidal saponin | |
| CN109651244A (en) | A kind of preparation method of niacin | |
| CN1308085A (en) | Preparation process of deoxycholeic acid of bear | |
| CN1673223A (en) | Dihydromyricitrin fatty ester preparing process | |
| DE60310683T2 (en) | PROCESS FOR THE PREPARATION OF 1- (MERCAPTOMETHYL) CYCLOPROPANIC ACIDIC ACID | |
| CN108440629A (en) | A method of preparing shellfish cholic acid intermediate difficult to understand and shellfish cholic acid difficult to understand | |
| CN114317663B (en) | Method for synthesizing ursodeoxycholic acid by utilizing feed after bilirubin extraction of pig gall |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20061101 |