CN112209984B - Improved process for the preparation of mesyl ergosterol - Google Patents
Improved process for the preparation of mesyl ergosterol Download PDFInfo
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- OILXMJHPFNGGTO-UHFFFAOYSA-N (22E)-(24xi)-24-methylcholesta-5,22-dien-3beta-ol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)C=CC(C)C(C)C)C1(C)CC2 OILXMJHPFNGGTO-UHFFFAOYSA-N 0.000 title claims abstract description 21
- RQOCXCFLRBRBCS-UHFFFAOYSA-N (22E)-cholesta-5,7,22-trien-3beta-ol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CCC(C)C)CCC33)C)C3=CC=C21 RQOCXCFLRBRBCS-UHFFFAOYSA-N 0.000 title claims abstract description 21
- OQMZNAMGEHIHNN-UHFFFAOYSA-N 7-Dehydrostigmasterol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CC(CC)C(C)C)CCC33)C)C3=CC=C21 OQMZNAMGEHIHNN-UHFFFAOYSA-N 0.000 title claims abstract description 21
- DNVPQKQSNYMLRS-NXVQYWJNSA-N Ergosterol Natural products CC(C)[C@@H](C)C=C[C@H](C)[C@H]1CC[C@H]2C3=CC=C4C[C@@H](O)CC[C@]4(C)[C@@H]3CC[C@]12C DNVPQKQSNYMLRS-NXVQYWJNSA-N 0.000 title claims abstract description 21
- -1 mesyl ergosterol Chemical compound 0.000 title claims abstract description 13
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- 238000000034 method Methods 0.000 title claims description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 58
- 238000006243 chemical reaction Methods 0.000 claims abstract description 40
- 238000003756 stirring Methods 0.000 claims abstract description 14
- DNVPQKQSNYMLRS-SOWFXMKYSA-N ergosterol Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H](CC[C@]3([C@H]([C@H](C)/C=C/[C@@H](C)C(C)C)CC[C@H]33)C)C3=CC=C21 DNVPQKQSNYMLRS-SOWFXMKYSA-N 0.000 claims abstract description 12
- 238000002425 crystallisation Methods 0.000 claims abstract description 9
- 230000008025 crystallization Effects 0.000 claims abstract description 9
- 239000002994 raw material Substances 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 28
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 14
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 239000007810 chemical reaction solvent Substances 0.000 claims description 3
- 239000002516 radical scavenger Substances 0.000 claims description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 2
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 239000007858 starting material Substances 0.000 claims 1
- 239000012295 chemical reaction liquid Substances 0.000 abstract description 7
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 abstract 1
- 239000007787 solid Substances 0.000 description 22
- 239000000243 solution Substances 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 13
- 239000005457 ice water Substances 0.000 description 10
- 239000013078 crystal Substances 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 6
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 239000012065 filter cake Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- IXVMHGVQKLDRKH-QHBHMFGVSA-N 24-Epibrassinolide Natural products C1OC(=O)[C@H]2C[C@H](O)[C@H](O)C[C@]2(C)[C@H]2CC[C@]3(C)[C@@H]([C@H](C)[C@@H](O)[C@H](O)[C@H](C)C(C)C)CC[C@H]3[C@@H]21 IXVMHGVQKLDRKH-QHBHMFGVSA-N 0.000 description 2
- IXVMHGVQKLDRKH-VRESXRICSA-N Brassinolide Natural products O=C1OC[C@@H]2[C@@H]3[C@@](C)([C@H]([C@@H]([C@@H](O)[C@H](O)[C@H](C(C)C)C)C)CC3)CC[C@@H]2[C@]2(C)[C@@H]1C[C@H](O)[C@H](O)C2 IXVMHGVQKLDRKH-VRESXRICSA-N 0.000 description 2
- UWDOJFUZFOFARA-ZFWJPAOCSA-N CC(C)[C@@H](C)/C=C/[C@@H](C)[C@@H](C(C1)S(C)(=O)=O)[C@]2(C)[C@@H]1C1=CC=C(C[C@H](CC3)O)[C@@]3(C)[C@H]1CC2 Chemical compound CC(C)[C@@H](C)/C=C/[C@@H](C)[C@@H](C(C1)S(C)(=O)=O)[C@]2(C)[C@@H]1C1=CC=C(C[C@H](CC3)O)[C@@]3(C)[C@H]1CC2 UWDOJFUZFOFARA-ZFWJPAOCSA-N 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- IXVMHGVQKLDRKH-KNBKMWSGSA-N brassinolide Chemical compound C1OC(=O)[C@H]2C[C@H](O)[C@H](O)C[C@]2(C)[C@H]2CC[C@]3(C)[C@@H]([C@H](C)[C@@H](O)[C@H](O)[C@@H](C)C(C)C)CC[C@H]3[C@@H]21 IXVMHGVQKLDRKH-KNBKMWSGSA-N 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229930002875 chlorophyll Natural products 0.000 description 1
- 235000019804 chlorophyll Nutrition 0.000 description 1
- ATNHDLDRLWWWCB-AENOIHSZSA-M chlorophyll a Chemical compound C1([C@@H](C(=O)OC)C(=O)C2=C3C)=C2N2C3=CC(C(CC)=C3C)=[N+]4C3=CC3=C(C=C)C(C)=C5N3[Mg-2]42[N+]2=C1[C@@H](CCC(=O)OC\C=C(/C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)[C@H](C)C2=C5 ATNHDLDRLWWWCB-AENOIHSZSA-M 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000029553 photosynthesis Effects 0.000 description 1
- 238000010672 photosynthesis Methods 0.000 description 1
- 239000005648 plant growth regulator Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 230000021749 root development Effects 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
Abstract
The application relates to methanesulfonic acidThe improved preparation method of the acyl ergosterol is characterized in that after the reaction is finished, water is dripped into the reaction liquid in three batches, the total water amount dripped in the three batches is 5-8 times of the mass of the ergosterol as the raw material compound, the first batch of water is firstly dripped until the reaction liquid is clear, then the second batch of water is dripped until crystallization just occurs, and the rest water is dripped into the third batch after the slow stirring is carried out for 0.5-2 hours.
Description
Technical Field
The present invention relates to an improved process for the preparation of mesyl ergosterol.
Background
Methylsulfonyl ergosterol is an important chemical feedstock and intermediate that can be used to prepare, for example, 24-epibrassinolide.
The 24-epibrassinolide belongs to a sterol plant growth regulator, has double effects of promoting plant cell division and delaying, can promote crop root development, enhance photosynthesis, improve the chlorophyll content of crops, promote crop metabolism, and assist the favorable growth of inferior parts of crops, thereby promoting crop growth.
Non-patent document 1 reports a process for producing methanesulfonylergosterol by dropping methanesulfonyl chloride in an ice-water bath at 10 ℃ and then crystallizing the reaction mixture by pouring the reaction mixture into ice-water (see pages 13 to 14 and 23 of non-patent document 1).
Non-patent document 2 describes that ergosterol represented by formula (1) is converted to a sulfonylate at 10 ℃ by adding methanesulfonyl chloride dropwise to a pyridine solution of ergosterol at 10 ℃ and reacting the mixture under stirring at 10 ℃ for 1 hour, and then introducing the reaction mixture into ice water under vigorous stirring to precipitate (see middle right column on page 2338 of non-patent document 2).
The above method is also reported in patent document CN10181211A, which describes in paragraph [0037 ]: ergosterol (200, 0.5 mol) was dissolved in 1.0L of anhydrous pyridine, the temperature was lowered to-5 to 10 ℃ and a pyridine solution of methanesulfonyl chloride (100g, 0.55mol, dissolved in 200mL of anhydrous pyridine) was slowly added dropwise. The reaction is stirred for 3-4h at 15 ℃. After the reaction was completed, the reaction solution was poured into a vigorously stirred bath of brine ice, and a large amount of solid was precipitated. Finally 290g of sulfonylated ergosterol was obtained with a yield of 104%.
Non-patent document 1: a academic thesis: (22E, 24R) -5 a-ergosta-2, 22-dien-6-one (Wang, 6.2004);
non-patent document 2: chem.1993,58,2338-2339.
Disclosure of Invention
The inventors of the present application found, when preparing methanesulfonylergosterol by referring to the above-mentioned literature methods: after the reaction is finished, the reaction solution is directly poured into ice water to precipitate out crystals, and the crystals are sticky and are not easy to filter and wash, so that the production efficiency is influenced. In addition, the reaction liquid after the reaction is finished contains solids, and in actual operation, the reaction liquid is directly poured into water, so that the problem of blockage of a pipeline or a discharge hole exists, and the operation is inconvenient.
In view of the above problems, the present invention aims to provide an improved process for the preparation of methanesulfonyl ergosterol.
Specifically, the present invention provides:
(1) The improved preparation method of the mesyl ergosterol is characterized in that after the reaction is finished, water is dripped into the reaction liquid in three batches, the total water amount dripped in the three batches is 5-8 times of the mass of the ergosterol as the raw material compound, the first batch of water is firstly dripped until the reaction liquid is clear, then the second batch of water is dripped until crystallization is just separated out, and the rest water is dripped into the third batch of water after the slow stirring is carried out for 0.5-2 hours.
(2) The method described in the above (1), wherein the total amount of water added dropwise is 6 to 7 times by mass as much as the ergosterol as the raw material compound.
(3) The method of (1) or (2) above, wherein the amount of water added dropwise in the first batch is 3% to 5% of the total amount of water, and the amount of water added dropwise in the second batch is 1% to 5% of the total amount of water.
(4) The method of any one of (1) to (3) above, wherein the temperature of the reaction solution is maintained at 30 ℃ or lower during the dropwise addition of water in the reaction solution.
(5) The process according to any one of the above (1) to (4), wherein after the addition of the remaining water to the third batch is completed, the mixture is further stirred for 0.5 to 1 hour.
(6) The process according to any one of the above (1) to (4), wherein the reaction solvent is one or more selected from the group consisting of pyridine, dichloromethane, acetone, tetrahydrofuran, ethyl acetate, N-dimethylformamide and N, N-dimethylacetamide.
(7) The process according to any one of the above (1) to (5), wherein the reaction is carried out in the presence of an acid-binding agent.
(8) The process according to the above (7), wherein the acid scavenger is pyridine, triethylamine, an alkali metal salt or an alkaline earth metal salt.
Detailed Description
The reaction route in the production method of the present invention is as shown above, and has been publicly reported, and various raw materials used therein are also known substances, and commercially available products can be used or the production can be carried out by a known method.
As described above, the methods reported in the prior art all comprise pouring the reaction solution directly into ice water for crystallization after the above reaction is completed. However, the present inventors found that the crystalline solid thus obtained was sticky, not easy to filter and wash, and long in time, thus lowering the production efficiency.
In addition, the inventor of the present application has found that after the reaction is completed, solids exist in the reaction solution, and if the reaction solution is directly poured into ice water for crystallization after the reaction, the solids not only cause blockage of pipelines and discharge ports, but also can be mixed or wrapped in the precipitated crystals to pollute target products.
The present inventors have found that the solid in the reaction solution is well soluble in water by filtering out the solid and attempting to dissolve it in water, and thus have presumed that the solid is a salt formed between the solvent or acid-binding agent used in the reaction and the reaction product hydrochloric acid. No matter organic alkali or inorganic alkali is used as an acid-binding agent, the salt is not easily dissolved in an organic solvent used for reaction after being salified with hydrochloric acid, and therefore, the salt is separated out. In addition, when pyridine is used as a solvent in the reaction, pyridine hydrochloride formed by pyridine and hydrochloric acid is not dissolved in pyridine and is precipitated as a solid.
In the improved method of the invention, water is dripped into the reaction liquid in three batches after the reaction is finished. The amount of water added dropwise in the three batches is 5 to 8 times, preferably 6 to 7 times, the mass of the ergosterol represented by formula (1) as the raw material.
The first batch of water is dripped until the reaction solution is dissolved clearly, so that the solid in the reaction solution can be eliminated, and the problems of target product pollution and pipe blockage caused by the solid are avoided. The amount of water added dropwise in the first batch is preferably 3 to 5% of the total amount of water.
The second batch of water is added dropwise until crystals are just precipitated in the reaction solution, and the amount of water added dropwise is preferably 1 to 5% of the total amount of water.
After the second batch of water is added dropwise, the reaction mixture is stirred slowly for 0.5 to 2 hours, preferably 1 to 1.5 hours. The slow stirring process is an integral crystallization process, and more solids with good crystal forms are gradually separated out, so that the finally obtained crystals have good filterability. If the stirring time is too short, the solid precipitation is insufficient in the whole crystallization process, and a large amount of solid is precipitated instantly after a large amount of water is added in the subsequent third batch, so that the obtained crystal form is poor, sticky and not easy to filter.
The slow stirring speed may be, for example, 30 to 40 revolutions per minute.
After slow stirring, the remaining water was added dropwise in a third batch, the purpose of this dropwise addition being to bring about more complete crystallization and increase the yield.
From the viewpoint of further improving the yield, it is preferable to further stir the third batch of water for 0.5 to 1 hour after the completion of the dropwise addition.
When a volatile solvent such as pyridine is used for the reaction, the temperature of the reaction mixture is preferably controlled to 30 ℃ or lower, more preferably 15 to 30 ℃ in the above-mentioned process of dropwise adding water. When the temperature is higher than 30 ℃, on one hand, the reaction solvent can volatilize to pollute the environment, and on the other hand, the residual methanesulfonyl chloride can react with water and release heat, so that the safety coefficient is low.
Preferred embodiments of the method of the present invention will be described below with reference to specific examples, but the present invention is not limited to these examples, and any modifications and alterations within the scope of the present invention are within the scope of the present invention.
Examples
Example 1
Adding 50g of ergosterol into a reaction bottle, adding 300mL of pyridine, stirring, cooling to 10 ℃ in an ice water bath, dropwise adding 42.5g of methanesulfonyl chloride, keeping the temperature of a reaction mixture below 10 ℃ in the dropwise adding process, removing the ice water bath after the dropwise adding is finished, stirring for reacting for 1.5h, and monitoring the completion of the reaction by HPLC. 10mL of water was added dropwise to the reaction mixture until the reaction mixture was clear, 5mL of water was added dropwise to precipitate a solid, the mixture was slowly stirred for 1 hour, and then the remaining 285mL of water was added dropwise to the reaction mixture, and the temperature of the reaction mixture was controlled to 30 ℃ or lower throughout the addition. After the dropwise addition, the mixture is further stirred for 30 minutes, filtered, and the filter cake is washed by 100mL of multiplied by 3 water and dried by pumping to obtain white granulated sugar-like solid. The filtration was fast, taking only 10 minutes, without stickiness, and the filter cake washed very well.
The HPLC detection conditions were as follows:
the instrument comprises the following steps: liquid chromatograph, UV detector;
a chromatographic column: ZORBAX BONUS-RP 250mm × 4.6mm × 5um;
mobile phase: 100% acetonitrile;
wavelength: 280nm; column temperature: 30 ℃; flow rate: 1.0ml/min.
Comparative example 1
Adding 50g of ergosterol into a reaction bottle, adding 300mL of pyridine, stirring, cooling to 10 ℃ in an ice water bath, dropwise adding 42.5g of methanesulfonyl chloride, keeping the temperature of a reaction mixture below 10 ℃ in the dropwise adding process, removing the ice water bath after the dropwise adding is finished, stirring for reacting for 1.5h, and monitoring the completion of the reaction by HPLC. 450mL of water is poured into the reaction solution to separate out a solid, the solid is filtered, and the filter cake is pulped by 750mL of water to wash the solid, so that a solid with a random shape is obtained. The solid precipitated therein was sticky and the filtration was slow, taking 1.5 hours.
Industrial applicability
The improved preparation method of the mesyl ergosterol treats the reaction mixture in a batch water adding mode after the reaction, not only improves the shape and filterability of the obtained crystal, but also avoids the solid existing in the reaction mixture before crystallization from being mixed or wrapped in the precipitated target product, and is beneficial to improving the purity of the target product.
Claims (7)
1. An improved preparation method of mesyl ergosterol is prepared by the following reaction, and is characterized in that after the reaction is finished, water is dripped into a reaction solution in three batches, the total water amount of the three batches of water is 5-8 times of the mass of the ergosterol as a raw material compound, the first batch of water is firstly dripped until the reaction solution is clear, then the second batch of water is dripped until crystallization just occurs, and after 0.5-2 hours of slow stirring, the rest water is dripped into the third batch of water, wherein the water amount of the first batch of water is 3-5% of the total water amount, the water amount of the second batch of water is 1-5% of the total water amount,
2. the process as claimed in claim 1, wherein the total amount of water added dropwise in three batches is 6 to 7 times by mass the amount of ergosterol as the starting compound.
3. The method of claim 1 or 2, wherein the temperature of the reaction solution is maintained below 30 ℃ during the addition of water to the reaction solution in a batch-wise manner.
4. The process of claim 1 or 2, wherein the third batch is stirred for a further 0.5 to 1 hour after the addition of the remaining water is completed.
5. The process according to claim 1 or 2, wherein the reaction solvent is one or more selected from the group consisting of pyridine, dichloromethane, acetone, tetrahydrofuran, ethyl acetate, N-dimethylformamide and N, N-dimethylacetamide.
6. The process of claim 1 or 2, wherein the reaction is carried out in the presence of an acid scavenger.
7. The process of claim 6, wherein the acid scavenger is pyridine, triethylamine, an alkali metal salt or an alkaline earth metal salt.
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|---|---|---|---|---|
| CN1708508A (en) * | 2002-11-08 | 2005-12-14 | 株式会社钟化 | Method of separating ergosterol |
| RU2272044C1 (en) * | 2004-09-13 | 2006-03-20 | Некоммерческое научно-производственное партнерство "Нэст М" | Method for preparing 24-epibrassinolide |
| CN101812114A (en) * | 2010-05-14 | 2010-08-25 | 上海威敌生化(南昌)有限公司 | Preparation method of 24-epibrassinolide |
| CN102659913A (en) * | 2012-04-20 | 2012-09-12 | 吴中兴 | Reductive composition for preparing 24-epibrassinolide |
| CN111004303A (en) * | 2019-12-17 | 2020-04-14 | 京博农化科技有限公司 | Method for synthesizing 24-epibrassinolide |
| CN111518154A (en) * | 2020-05-29 | 2020-08-11 | 郑州郑氏化工产品有限公司 | Preparation method of 24-epibrassinol intermediate |
-
2020
- 2020-11-18 CN CN202011290973.5A patent/CN112209984B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1708508A (en) * | 2002-11-08 | 2005-12-14 | 株式会社钟化 | Method of separating ergosterol |
| RU2272044C1 (en) * | 2004-09-13 | 2006-03-20 | Некоммерческое научно-производственное партнерство "Нэст М" | Method for preparing 24-epibrassinolide |
| CN101812114A (en) * | 2010-05-14 | 2010-08-25 | 上海威敌生化(南昌)有限公司 | Preparation method of 24-epibrassinolide |
| CN102659913A (en) * | 2012-04-20 | 2012-09-12 | 吴中兴 | Reductive composition for preparing 24-epibrassinolide |
| CN111004303A (en) * | 2019-12-17 | 2020-04-14 | 京博农化科技有限公司 | Method for synthesizing 24-epibrassinolide |
| CN111518154A (en) * | 2020-05-29 | 2020-08-11 | 郑州郑氏化工产品有限公司 | Preparation method of 24-epibrassinol intermediate |
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