CN101486748A - Preparation of 5,7-diene cholesterol - Google Patents
Preparation of 5,7-diene cholesterol Download PDFInfo
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- CN101486748A CN101486748A CNA2008100592992A CN200810059299A CN101486748A CN 101486748 A CN101486748 A CN 101486748A CN A2008100592992 A CNA2008100592992 A CN A2008100592992A CN 200810059299 A CN200810059299 A CN 200810059299A CN 101486748 A CN101486748 A CN 101486748A
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- cholesteryl ester
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Abstract
The invention discloses a preparation method of 5, 7-diene cholesteryl ester which serves as important intermediate in production of vitamin D3. The preparation method adopts a special effective catalyzer which is the combination of a superfine sodium carbonate and a triethyl orthoformate. Compared with the prior art, the preparation method obviously has the advantages of less side effect, higher reaction and recovery rate, lower cost and less environmental pollution.
Description
Technical field
The present invention relates to the preparation method of important intermediate 5,7-diene cholesteryl ester of Vitamin D3 500,000 I.U/GM.
Background technology
5,7-diene cholesteryl ester is for generating the important intermediate of pre-D3 (7-dehydrocholesterol), and reaction formula is as follows:
5,7-diene 4,6-diene
The employed catalyzer of this reaction traditional method is benzenethiol, peroxy acid, triethylamine, liquefied ammonia, alkaline metal fluoride cpd, pyridines etc.Wherein reported in literature is the most effective is liquefied ammonia.Adopt above-mentioned catalyzer, target product 5,7-diene cholesteryl ester selectivity is bad, and yield is about 58-62%, and a spot of water is unfavorable for that reaction carries out fully in the reaction system, and especially triethylamine, liquefied ammonia are very big to environmental influence.
At the existing problem of above-mentioned catalyzer, we have sought a kind of effective catalyzer: ultra-fine yellow soda ash and triethyl orthoformate combination catalyst.
Summary of the invention
Technical problem to be solved by this invention is to overcome the defective that above-mentioned prior art exists, provide that a kind of raw material is easy to get, the gentle easily control of reaction conditions 5, the preparation method of 7-diene cholesteryl ester, select special effective catalyzer for use: ultra-fine yellow soda ash and triethyl orthoformate combination catalyst, what play debromination is yellow soda ash, through be ground into ultra-fine after, increase its specific surface area, can improve speed of response, increase reaction yield.Catalyzer of the present invention is the catalyzer that a kind of selectivity is good, security is good, and the reaction conditions gentleness is not subject to poisoning of impurity, and environmentally friendly.
For this reason, the present invention adopts following technical scheme: a kind of 5, the preparation method of 7-diene cholesteryl ester, in the presence of organic solvent, with catalyst 7-bromo cholesteryl ester, the crystallization of reaction postcooling, 5,7-diene cholesteryl ester.
As the further of technique scheme improved and replenish, the present invention takes following technical measures:
The preparation method of above-mentioned 5,7-diene cholesteryl ester, catalyzer is the combination catalyst of ultra-fine yellow soda ash and triethyl orthoformate, and the particle diameter of the ultra-fine yellow soda ash of catalyzer is the 50-200 order, and this catalyzer has improved speed of response greatly, has increased reaction yield.
The preparation method of above-mentioned 5,7-diene cholesteryl ester is characterized in that the mol ratio of 7-bromo cholesteryl ester and catalyzer (calculating with triethyl orthoformate) is 1:0.3-2.0, preferred 1:0.5-0.7.
Above-mentioned 5, the preparation method of 7-diene cholesteryl ester, reaction raw materials 7-bromo cholesteryl ester is 7-bromo cholesterol benzoate and 7-bromo cholesterol acetate, it is aromatic hydrocarbons and acid amides that reaction solvent is selected organic solvent for use, particularly dimethylbenzene, a trimethylbenzene and DMF temperature of reaction are 80 ℃-150 ℃, preferred 100-130 ℃.
This reaction produces a spot of water and is steamed after the triethyl orthoformate reaction, thereby has guaranteed to remain in the reaction system anhydrous, has avoided the influence of water to reaction yield, has also promoted molecular balance to move to target product.Use its target product 5,7-diene cholesteryl ester yield of aforesaid combination catalyzer to be about 75-78%.
The present invention has following beneficial effect: the reaction conditions gentleness of this method, and side reaction is few, and flow process is short, and technological operation is simple; Environmental pollution is few, has avoided the pollution to water of pollution that triethylamine, liquefied ammonia cause air and metal fluoride.The reaction yield height, production cost is low, is fit to scale operation.
The invention will be further described below in conjunction with embodiment.
Embodiment
Embodiment 1
Get 7-bromo cholesterol benzoate, 30.0 grams (content 85%, 0.0447mol) after the 500mL four-hole bottle adds vacuum-drying, dimethylbenzene 200ML, ultra-fine yellow soda ash 3.0 grams, triethyl orthoformate 4mL (0.0243mol), be warming up to 125 ℃ of timing insulations 2 hours, be warming up to 130 ℃ again and continued insulation reaction 2 hours, collection unit is divided fraction, and the raw material peak is considered as reacting completely less than 2.0% after testing.Reaction is finished and to be cooled to room temperature and to filter, and decompression and solvent recovery is to doing, 26.4 grams of weighing (content about 65%, yield 78.7%).Get 5 through acetone recrystallization, get Precalciferol3 (7-dehydrocholesterol) after 7-diene cholesterol benzoate (content the reaches 85%) saponification reaction.
Embodiment 2
Get 7-bromo cholesterol acetate, 30.0 grams (content 85%, 0.0502mol) after the 500mL four-hole bottle adds vacuum-drying, dimethylbenzene 200ML, ultra-fine yellow soda ash 3.0 grams, triethyl orthoformate 5mL (0.0304mol), be warming up to 115 ℃ of timing insulations 4 hours, collection unit is divided fraction, and the raw material peak is considered as reacting completely less than 1.0% after testing.Reaction is finished and to be cooled to room temperature and to filter, and decompression and solvent recovery is to doing, 25.0 grams of weighing (content about 65%, yield 76.0%).
Embodiment 3
The particle diameter of combination catalyst yellow soda ash is to the influence of product yield
| The particle diameter of yellow soda ash | Yellow soda ash (industrial goods) | Ultra-fine yellow soda ash (100 order) |
| Product yield % | 70 | 78.5 |
Embodiment 4
Be that raw material is adjusted the influence of the amount of different catalysts (triethyl orthoformate) to yield with 7-bromo cholesterol benzoate below:
| Raw material and catalyst molar ratio | Assembly catalyze molar product yield % | Single catalyst article molar yield % |
| 1.0:0.54 | 78.7 | 65 |
| 1.0:0.61 | 76.0 | 64 |
| 1.0:0.30 | 66.8 | 56 |
| 1.0:1.0 | 69.1 | 57 |
| 1.0:2.0 | 65.2 | 55 |
Claims (10)
1, a kind of preparation method of 5,7-diene cholesteryl ester is in the presence of organic solvent, with catalyst 7-bromo cholesteryl ester, the crystallization of reaction postcooling gets 5,7-diene cholesteryl ester, it is characterized in that the catalyzer that reacts used is yellow soda ash and triethyl orthoformate combination catalyst.
2, the preparation method of 5,7-diene cholesteryl ester according to claim 1 is characterized in that catalyzer is the combination catalyst of ultra-fine yellow soda ash and triethyl orthoformate.
3, the preparation method of 5,7-diene cholesteryl ester according to claim 2, the particle diameter that it is characterized in that the ultra-fine yellow soda ash of combination catalyst is the 50-200 order.
4, the preparation method of 5,7-diene cholesteryl ester according to claim 1 is characterized in that the mol ratio of 7-bromo cholesteryl ester and catalyzer (calculating with triethyl orthoformate) is 1:0.3-2.0.
5, the preparation method of 5,7-diene cholesteryl ester according to claim 4 is characterized in that the mol ratio of 7-bromo cholesteryl ester and catalyzer (calculating with triethyl orthoformate) is 1:0.5-0.7.
6, the preparation method of 5,7-diene cholesteryl ester according to claim 1 is characterized in that described organic solvent is aromatic hydrocarbons and acid amides.
7, the preparation method of 5,7-diene cholesteryl ester according to claim 6 is characterized in that described organic solvent is dimethylbenzene, a trimethylbenzene and DMF.
8, the preparation method of 5,7-diene cholesteryl ester according to claim 1 is characterized in that temperature of reaction is 80 ℃-150 ℃.
9, the preparation method of 5,7-diene cholesteryl ester according to claim 8 is characterized in that temperature of reaction is 100 ℃-130 ℃.
10, the preparation method of 5,7-diene cholesteryl ester according to claim 1 is characterized in that described raw material 7-bromo cholesteryl ester is 7-bromo cholesterol benzoate and 7-bromo cholesterol acetate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008100592992A CN101486748B (en) | 2008-01-15 | 2008-01-15 | Preparation method of preparation of 5,7-diene cholesterol |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008100592992A CN101486748B (en) | 2008-01-15 | 2008-01-15 | Preparation method of preparation of 5,7-diene cholesterol |
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| CN101486748A true CN101486748A (en) | 2009-07-22 |
| CN101486748B CN101486748B (en) | 2011-11-02 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102002518A (en) * | 2010-10-28 | 2011-04-06 | 浙江大学 | Method for preparing 7beta-hydroxyl-3beta cholesterol acetate from hydroxylase 3beta-cholesterol acetate |
| KR20160108599A (en) * | 2011-07-28 | 2016-09-19 | 산산 왕 | Composite collagen sponge and preparation method thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SU910654A1 (en) * | 1980-07-31 | 1982-03-07 | Ордена Трудового Красного Знамени Институт Биохимии Им.А.В.Палладина Ан Усср | Process for producing 7-dehydrocholesterol benzoate |
| EP0084199B1 (en) * | 1982-01-14 | 1987-04-29 | Duphar International Research B.V | Method of preparing delta 5,7-steroids |
-
2008
- 2008-01-15 CN CN2008100592992A patent/CN101486748B/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102002518A (en) * | 2010-10-28 | 2011-04-06 | 浙江大学 | Method for preparing 7beta-hydroxyl-3beta cholesterol acetate from hydroxylase 3beta-cholesterol acetate |
| CN102002518B (en) * | 2010-10-28 | 2015-05-13 | 浙江大学 | Method for preparing 7beta-hydroxyl-3beta cholesterol acetate from hydroxylase 3beta-cholesterol acetate |
| KR20160108599A (en) * | 2011-07-28 | 2016-09-19 | 산산 왕 | Composite collagen sponge and preparation method thereof |
| KR101717266B1 (en) | 2011-07-28 | 2017-03-16 | 산산 왕 | Composite collagen sponge and preparation method thereof |
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| CN101486748B (en) | 2011-11-02 |
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