CN101875664B - Method for preparing ergocalciferol double-projection product - Google Patents
Method for preparing ergocalciferol double-projection product Download PDFInfo
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- CN101875664B CN101875664B CN 200910050205 CN200910050205A CN101875664B CN 101875664 B CN101875664 B CN 101875664B CN 200910050205 CN200910050205 CN 200910050205 CN 200910050205 A CN200910050205 A CN 200910050205A CN 101875664 B CN101875664 B CN 101875664B
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- MECHNRXZTMCUDQ-UHFFFAOYSA-N Vitamin D2 Natural products C1CCC2(C)C(C(C)C=CC(C)C(C)C)CCC2C1=CC=C1CC(O)CCC1=C MECHNRXZTMCUDQ-UHFFFAOYSA-N 0.000 title claims abstract description 56
- 229960002061 ergocalciferol Drugs 0.000 title claims abstract description 56
- 235000001892 vitamin D2 Nutrition 0.000 title claims abstract description 56
- 239000011653 vitamin D2 Substances 0.000 title claims abstract description 56
- MECHNRXZTMCUDQ-RKHKHRCZSA-N vitamin D2 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)/C=C/[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)CCC1=C MECHNRXZTMCUDQ-RKHKHRCZSA-N 0.000 title claims abstract description 56
- 238000000034 method Methods 0.000 title claims abstract description 23
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims abstract description 22
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 claims abstract description 20
- 239000007788 liquid Substances 0.000 claims abstract description 13
- 238000001953 recrystallisation Methods 0.000 claims abstract description 9
- 239000002904 solvent Substances 0.000 claims abstract description 7
- 150000001335 aliphatic alkanes Chemical class 0.000 claims abstract description 5
- 238000006243 chemical reaction Methods 0.000 claims description 27
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 20
- 239000007789 gas Substances 0.000 claims description 16
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 14
- 230000004224 protection Effects 0.000 claims description 14
- 150000002460 imidazoles Chemical class 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 9
- 229910052786 argon Inorganic materials 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 5
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 2
- 238000005265 energy consumption Methods 0.000 abstract description 3
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 238000005580 one pot reaction Methods 0.000 abstract description 3
- 238000007039 two-step reaction Methods 0.000 abstract description 3
- 238000005516 engineering process Methods 0.000 abstract description 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 abstract 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 9
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 8
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 7
- 238000004440 column chromatography Methods 0.000 description 7
- 235000005282 vitamin D3 Nutrition 0.000 description 7
- 239000011647 vitamin D3 Substances 0.000 description 7
- 229940021056 vitamin d3 Drugs 0.000 description 7
- 239000007787 solid Substances 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 229940125904 compound 1 Drugs 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- HHSARRMUXPDGJD-UHFFFAOYSA-N butyl(dimethyl)silicon Chemical group CCCC[Si](C)C HHSARRMUXPDGJD-UHFFFAOYSA-N 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 150000003722 vitamin derivatives Chemical class 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- DIPPFEXMRDPFBK-UHFFFAOYSA-N Vitamin D4 Natural products C1CCC2(C)C(C(C)CCC(C)C(C)C)CCC2C1=CC=C1CC(O)CCC1=C DIPPFEXMRDPFBK-UHFFFAOYSA-N 0.000 description 1
- 229960002535 alfacalcidol Drugs 0.000 description 1
- OFHCOWSQAMBJIW-AVJTYSNKSA-N alfacalcidol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C OFHCOWSQAMBJIW-AVJTYSNKSA-N 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 230000008468 bone growth Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 230000002308 calcification Effects 0.000 description 1
- 229960005084 calcitriol Drugs 0.000 description 1
- 235000020964 calcitriol Nutrition 0.000 description 1
- 239000011612 calcitriol Substances 0.000 description 1
- GMRQFYUYWCNGIN-NKMMMXOESA-N calcitriol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C GMRQFYUYWCNGIN-NKMMMXOESA-N 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 238000011210 chromatographic step Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 208000003532 hypothyroidism Diseases 0.000 description 1
- 230000002989 hypothyroidism Effects 0.000 description 1
- 230000031891 intestinal absorption Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 208000007442 rickets Diseases 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- DIPPFEXMRDPFBK-JPWDPSJFSA-N vitamin D4 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CC[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)CCC1=C DIPPFEXMRDPFBK-JPWDPSJFSA-N 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses an improved method for preparing an ergocalciferol double-projection product, which is characterized by comprising the following steps: a) adding ergocalciferol in liquid sulfur dioxide, and respectively reacting at minus 25-minus 10 DEG C, at room temperature and at 30-40 DEG C; b) directly adding tert-Butyldimethylsilyl chloride and imidazole to react; and c) adding alkane solvent, and recrystallizing to obtain a target product. The invention adopts a one-pot method to merge at two-step reaction into one-step reaction, thus lowering the solvent cost and reducing other energy consumption at the same time; and a recrystallization method instead of column chromatograph is adopted to obtain the target product so as to enable the method to be applicable to industrialized production in technology.
Description
Technical field
The present invention relates to the preparation method of ergocalciferol double-projection product (9.10-open loop courage steroid-5,7 (E) 10,19,22 (E)-tetraene-3S-tertiary butyl dimethyl-silicon ether sulfurous gas adducts).
Background technology
Vitamins D on the classical meaning refers to some treatments and prevents rachitic sterol material that they comprise vitamin D2 and vitamin d, Vitamin D3 500,000 I.U/GM and Dry Vitamin D3 100 cws (perhaps vitamin D4).Vitamin D2 and Vitamin D3 500,000 I.U/GM have material impact to calcium, phosphorus metabolism and children's bone growth, and they can promote calcium, phosphorus in intestinal absorption and the normal calcification of bone, are the main medicine for the treatment of rickets, richets and hypothyroidism clinically.
Although vitamin D2 and Vitamin D3 500,000 I.U/GM have same effect, the activity intensity difference, comparatively speaking, the intensity of Vitamin D3 500,000 I.U/GM is greater than vitamin D2, and some active metabolites of Vitamin D3 500,000 I.U/GM, as calcitriol, Alfacalcidol is active better.Utilize the vitamin D2 characteristics identical with the Vitamin D3 500,000 I.U/GM basic framework; some active metabolites with the semi-synthetic Vitamin D3 500,000 I.U/GM of vitamin D2 are more feasible methods; but in building-up process owing to need use oxidizing reaction; so need be with susceptible 5 before oxidation; 6 and 10,19 conjugated double bond and hydroxyl are protected.
Document J.Org.Chem., 1993,58 (6): 1496-1500 discloses a kind of with 5 of sulfurous gas protection vitamin D2,6 and 10,19 conjugated double bond and with the method for the hydroxyl of TERT-BUTYL DIMETHYL CHLORO SILANE protection vitamin D2 comprise the steps: with dry ice sulfur dioxide gas to be cooled to liquid, the vitamin D2 that adds the methylene dichloride dissolving then, behind-10 ℃ of reaction 1.25h, room temperature reaction, evaporate to dryness; And then add the methylene dichloride dissolving, and adding a certain proportion of TERT-BUTYL DIMETHYL CHLORO SILANE and imidazoles, room temperature reaction spends the night, and handles and obtains faint yellow solid, and column chromatography obtains target product, pure product total recovery 94%.The shortcoming of this method is reaction loaded down with trivial details (two-step reaction), the time long (spending the night), and use column chromatography method, be unfavorable for industrialization.
Document Tetrahedron; 1987; 43 (20): 4609-4619 also discloses with 5 of sulfurous gas protection vitamin D2; 6 and 10; 19 conjugated double bond and the method for protecting the hydroxyl of vitamin D2 with TERT-BUTYL DIMETHYL CHLORO SILANE; comprise the steps: vitamin D2 is joined in the liquid sulfurous gas; reflux 0.5h; evaporate to dryness; with the DMF dissolving, add a certain proportion of TERT-BUTYL DIMETHYL CHLORO SILANE and imidazoles, 20 ℃ of reaction 1.5h; handle the back column chromatography and obtain target product, pure product total recovery 94%.The shortcoming of this method is that reaction is loaded down with trivial details, and the reagent dimethyl formamide of selecting for use is difficult to handle with respect to methylene dichloride, and also uses column chromatography method, is unfavorable for industrialization.
Document Chem.Pha rm.Bull.; 1995; 43 (2): 189-192 also discloses 5,6 and 10,19 conjugated double bond and the method for protecting the hydroxyl of vitamin D2 with TERT-BUTYL DIMETHYL CHLORO SILANE with sulfurous gas protection vitamin D2; comprise the steps: vitamin D2 is joined in the liquid sulfurous gas; reflux 0.5h, room temperature reaction 0.5h, evaporate to dryness; add ethyl acetate and sodium bicarbonate aqueous solution; extract washing, drying; evaporate to dryness; with the DMF dissolving, add a certain proportion of TERT-BUTYL DIMETHYL CHLORO SILANE and imidazoles, room temperature reaction 1.5h; handle the back column chromatography and obtain target product, pure product total recovery 100%.The shortcoming aftertreatment of this method is more loaded down with trivial details, and the reagent dimethyl formamide of selecting for use is difficult to handle with respect to methylene dichloride, and also uses column chromatography method, is unfavorable for industrialization.
Therefore; still need that active development is easy and simple to handle, less energy consumption, especially can adapt to suitability for industrialized production with 5 of sulfurous gas protection vitamin D2; 6 and 10,19 conjugated double bond and the method for protecting the hydroxyl of vitamin D2 with TERT-BUTYL DIMETHYL CHLORO SILANE.
Summary of the invention
The invention provides a kind of preparation method of improved ergocalciferol double-projection product, this method makes with 5 of sulfurous gas protection vitamin D2,6 and 10,19 conjugated double bond and finish for one pot with the hydroxyl two steps reaction of TERT-BUTYL DIMETHYL CHLORO SILANE protection vitamin D2; This method is got rid of reaction rear pillar chromatographic step simultaneously, utilizes repeatedly the method for recrystallization to obtain target product, makes it be beneficial to industrialization.
Two protections of vitamin D2 of the present invention refer to 5,6 and 10,19 conjugated double bond and the hydroxyl of protecting vitamin D2 with TERT-BUTYL DIMETHYL CHLORO SILANE with sulfurous gas protection vitamin D2.
The chemical name of ergocalciferol double-projection product of the present invention (seeing following structure 1) is 9.10-open loop courage steroid-5,7 (E) 10,19,22 (E)-tetraene-3S-tertiary butyl dimethyl-silicon ether sulfurous gas adducts.
The preparation method of ergocalciferol double-projection product of the present invention is characterized in that, this method comprises the steps:
A) vitamin D2 is joined in the liquid sulfur dioxide, respectively at reacting under-25 ℃ to-10 ℃ temperature, under the room temperature and under 30 ℃-40 ℃;
B) directly add TERT-BUTYL DIMETHYL CHLORO SILANE and imidazoles reacts;
C) add alkane solvents and carry out recrystallization, obtain target product.
According to the present invention, the vitamin D2 in the step a) can dissolve with methylene dichloride.
According to the present invention, the described reaction of step a) is preferably carried out under argon gas or nitrogen protection, and this is because the raw material vitamin D2 is variable in air; And can also drive unnecessary sulfurous gas out of with argon gas or nitrogen protection, unaffected with the reaction that guarantees the protection hydroxyl.
According to the present invention, vitamin D2 joins in the liquid sulfur dioxide, at first under-25 ℃ to-10 ℃ temperature in the reaction 1.5-2.0h; At room temperature react 0.5-1.0h; Be heated to 30 ℃-40 ℃ reaction 0.5-1.0h down then.Preferably, according to the present invention, vitamin D2 joins in the liquid sulfur dioxide, at first reaction 1.5h in-15 ℃ are descended; Place then under the room temperature and react 0.5h; Be heated to 30 ℃ of reaction 0.75h down then.
According to the present invention, the liquid sulfur dioxide in the step a) is q.s; The molar weight that adds TERT-BUTYL DIMETHYL CHLORO SILANE in the step b) is 1.05-1.3 times of vitamin D2; The molar weight that adds imidazoles is 1.3-2.2 times of vitamin D2.Preferably, according to the present invention, the molar weight that adds TERT-BUTYL DIMETHYL CHLORO SILANE in the step b) is 1.1 times of vitamin D2; The molar weight that adds imidazoles is 2.2 times of vitamin D2.
According to the present invention, described alkane solvents can be normal hexane, normal heptane or its mixture.
The present invention is with 5,6 of sulfurous gas protection vitamin D2 and 10,19 conjugated double bond and protect the reaction formula of hydroxyl of vitamin D2 as follows with TERT-BUTYL DIMETHYL CHLORO SILANE:
Above target product 1 is ergocalciferol double-projection product.
The present invention is with respect to the advantage of prior art:
1) adopts one kettle way that two-step reaction is merged into a step, not only reduced solvent cost, also reduced other energy consumptions simultaneously;
2) owing to got rid of column chromatography, adopt repeatedly the method for recrystallization to obtain target product, make it technically can suitability for industrialized production.
Embodiment
Embodiment 1
Vitamin D2 12.5g (31.6mmol) with the dissolving of the methylene dichloride of 100ml, is joined in the liquid sulfur dioxide of q.s, and argon shield keeps ℃ down reaction 1.5h of temperature-25, is put in then and reacts 0.5h under the room temperature, is heated to 30 ℃ of reaction 0.5h; The TERT-BUTYL DIMETHYL CHLORO SILANE (TBDMSC1) and 3.2g (47.4mmol) imidazoles that directly add 5.0g (33.2mmol); stir 2h; aftertreatment; evaporate to dryness obtains flaxen solid; add repeatedly recrystallization of normal hexane; get ergocalciferol double-projection product (compound 1) 17.5g, yield 96.5% (yield calculates with vitamin D2).
Embodiment 2
Vitamin D2 12.5g (31.6mmol) with the dissolving of the methylene dichloride of 100ml, is joined in the liquid sulfur dioxide of q.s, and argon shield keeps ℃ down reaction 2.0h of temperature-10, is put in then and reacts 1.0h under the room temperature, is heated to 40 ℃ of reaction 0.75h; The TERT-BUTYL DIMETHYL CHLORO SILANE (TBDMSC1) and 4.7g (69.5mmol) imidazoles that directly add 5.2g (34.8mmol); stir 2h; aftertreatment; evaporate to dryness obtains flaxen solid; add repeatedly recrystallization of normal heptane; get ergocalciferol double-projection product (compound 1) 17.5g, yield 97.8% (yield calculates with vitamin D2).
Embodiment 3
Vitamin D2 25g (63.1mmol) with the dissolving of the methylene dichloride of 200ml, is joined in the liquid sulfur dioxide of q.s, and argon shield keeps ℃ down reaction 2.0h of temperature-10, is put in then and reacts 1.0h under the room temperature, is heated to 40 ℃ of reaction 1.0h; The TERT-BUTYL DIMETHYL CHLORO SILANE (TBDMSC1) and 9.4g (139.0mmol) imidazoles that directly add 10.4g (69.6mmol); stir 2.0h; aftertreatment; evaporate to dryness obtains flaxen solid; add normal heptane: normal hexane=more than 20: 1 recrystallization; get ergocalciferol double-projection product (compound 1) 17.5g, yield 98.1% (yield calculates with vitamin D2).
Embodiment 4
Vitamin D2 25g (63.1mmol) with the dissolving of the methylene dichloride of 200ml, is joined in the liquid sulfur dioxide of q.s, and argon shield keeps answering 2.0h under the temperature-15 ℃, is put in then under the room temperature and reacts 1.0h, is heated to 35 ℃ of reaction 1.0h; The TERT-BUTYL DIMETHYL CHLORO SILANE (TBDMSC1) and 9.4g (139.0mmol) imidazoles that directly add 10.4g (69.6mmol); stir 2h; aftertreatment; evaporate to dryness obtains flaxen solid; add normal heptane: normal hexane=more than 50: 1 recrystallization; get ergocalciferol double-projection product (compound 1) 17.5g, yield 97.5% (yield calculates with vitamin D2).
Claims (5)
1. the preparation method of ergocalciferol double-projection product is characterized in that, this method comprises the steps:
A) will join in the liquid sulfur dioxide with the vitamin D2 of methylene dichloride dissolving, react 0.5-1.0h down respectively at reaction 0.5-1.0h under reaction 1.5-2.0 hour, the room temperature under-25 ℃ to-10 ℃ temperature and 30 ℃-40 ℃;
B) directly add TERT-BUTYL DIMETHYL CHLORO SILANE and imidazoles reacts;
C) add alkane solvents and carry out recrystallization, obtain target product.
2. preparation method according to claim 1 is characterized in that, described being reflected under argon gas or the nitrogen protection of step a) carried out.
3. preparation method according to claim 1 is characterized in that, the molar weight that adds TERT-BUTYL DIMETHYL CHLORO SILANE in the step b) is 1.05-1.3 times of vitamin D2.
4. preparation method according to claim 1 is characterized in that, the molar weight that adds imidazoles in the step b) is 1.3-2.1 times of vitamin D2.
5. preparation method according to claim 1 is characterized in that, the alkane solvents in the step c) is normal hexane, normal heptane or its mixture.
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| CN 200910050205 CN101875664B (en) | 2009-04-28 | 2009-04-28 | Method for preparing ergocalciferol double-projection product |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6359012B1 (en) * | 1999-12-22 | 2002-03-19 | Bone Care International, Inc. | Method for making 24(S)-hydroxyvitamin D2 |
| CN1948283A (en) * | 2005-10-14 | 2007-04-18 | 台耀化学股份有限公司 | Preparation method of vitamin D derivative |
-
2009
- 2009-04-28 CN CN 200910050205 patent/CN101875664B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6359012B1 (en) * | 1999-12-22 | 2002-03-19 | Bone Care International, Inc. | Method for making 24(S)-hydroxyvitamin D2 |
| CN1948283A (en) * | 2005-10-14 | 2007-04-18 | 台耀化学股份有限公司 | Preparation method of vitamin D derivative |
Non-Patent Citations (4)
| Title |
|---|
| Kaori Ando, et al..An improved synthesis of 24,24-difluoro-1α,25-dihydroxyvitamin D3 from readily available vitamin D2..《Chem. Pharm. Bull.》.1995,第43卷(第2期),189-192. * |
| KaoriAndo et al..An improved synthesis of 24 |
| Martin J.Calverley,et al..A biologically active vitamin D metabilite analogue..《Tetrahedron》.1987,第43卷(第20期),4609-4619. * |
| Satish C. Choudhry,et al..Synthesis of a biologically active vitamin-D2 metabolite..《J. Org. Chem.》.1993,第58卷1496-1500. * |
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| CN101875664A (en) | 2010-11-03 |
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