CN102603724B - Method for purifying and refining dimethoxy taxane compound - Google Patents
Method for purifying and refining dimethoxy taxane compound Download PDFInfo
- Publication number
- CN102603724B CN102603724B CN201210038631.3A CN201210038631A CN102603724B CN 102603724 B CN102603724 B CN 102603724B CN 201210038631 A CN201210038631 A CN 201210038631A CN 102603724 B CN102603724 B CN 102603724B
- Authority
- CN
- China
- Prior art keywords
- dimethoxy
- product
- equivalent
- ethyl acetate
- reaction
- 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.)
- Active
Links
- 238000000034 method Methods 0.000 title claims abstract description 18
- 229940123237 Taxane Drugs 0.000 title claims abstract description 13
- -1 dimethoxy taxane compound Chemical class 0.000 title abstract description 3
- 238000007670 refining Methods 0.000 title abstract 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 54
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract description 18
- 238000006243 chemical reaction Methods 0.000 claims abstract description 17
- 150000002148 esters Chemical class 0.000 claims abstract description 9
- 238000010898 silica gel chromatography Methods 0.000 claims abstract description 8
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 20
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 15
- 230000006837 decompression Effects 0.000 claims description 13
- 238000000746 purification Methods 0.000 claims description 11
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
- 125000001891 dimethoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 8
- 229960003328 benzoyl peroxide Drugs 0.000 claims description 8
- 239000012046 mixed solvent Substances 0.000 claims description 8
- 239000000741 silica gel Substances 0.000 claims description 8
- 229910002027 silica gel Inorganic materials 0.000 claims description 8
- 229960001866 silicon dioxide Drugs 0.000 claims description 8
- 239000012074 organic phase Substances 0.000 claims description 7
- 238000003756 stirring Methods 0.000 claims description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 claims description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
- KPZSTOVTJYRDIO-UHFFFAOYSA-K trichlorocerium;heptahydrate Chemical compound O.O.O.O.O.O.O.Cl[Ce](Cl)Cl KPZSTOVTJYRDIO-UHFFFAOYSA-K 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 4
- 239000003480 eluent Substances 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims 1
- 239000000047 product Substances 0.000 abstract description 35
- 239000012043 crude product Substances 0.000 abstract description 9
- 239000006227 byproduct Substances 0.000 abstract description 4
- 238000005406 washing Methods 0.000 abstract description 4
- 238000013329 compounding Methods 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- 239000003208 petroleum Substances 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 15
- 238000004587 chromatography analysis Methods 0.000 description 6
- 238000000926 separation method Methods 0.000 description 6
- MSVWUXLRSKRKFZ-IPMKNSEASA-N (2r,4s,5r)-2-(4-methoxyphenyl)-3-[(2-methylpropan-2-yl)oxycarbonyl]-4-phenyl-1,3-oxazolidine-5-carboxylic acid Chemical compound C1=CC(OC)=CC=C1[C@@H]1N(C(=O)OC(C)(C)C)[C@@H](C=2C=CC=CC=2)[C@H](C(O)=O)O1 MSVWUXLRSKRKFZ-IPMKNSEASA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 description 1
Abstract
The invention relates to a method for purifying and refining a dimethoxy taxane compound, in particular to the method for purifying and refining 3-tert-butoxycarbonyl-2-p-methoxyphenyl-4-phenyl-(2R,4S,5R)-1,3-oxazolidinyl-5-carboxylic acid-4alpha-acetoxyl-2alpha-benzoyloxy-5beta,20-epoxy-1beta-hydroxy-9-oxo-7beta,10beta-dimethoxy-11-taxadiene-13alpha ester. The method comprises the following steps: carrying out silica-gel column chromatography on a crude product; eluting the crude product by using petroleum ether/ethyl acetate; collecting the eluate; concentrating to obtain an initial product; allowing reaction between a compounding reagent with the initial product; washing; and refining to prepare the required product. The method is simple in operation and easy for industrial production; and byproducts cannot be generated in the reaction process, so that the reaction yield is increased and the product purity is improved.
Description
Technical field
The present invention relates to a kind of method of dimethoxy bearing taxanes purification refine, be specifically related to a kind of 3-tertbutyloxycarbonyl-2-p-methoxyphenyl-4-phenyl-(2R, 4S, 5R)-1,3-oxazolidine-5-carboxylic acid 4 α-acetoxyl group-2 α-benzoyloxy-5 β, 20-epoxy-1 beta-hydroxy-9-oxygen-7 β, the process for purification refine of 10 β-dimethoxy-11-yew alkene-13 α ester.
Background technology
3-tertbutyloxycarbonyl-2-p-methoxyphenyl-4-phenyl-(2R, 4S, 5R)-1,3-oxazolidine-5-carboxylic acid 4 α-acetoxyl group-2 α-benzoyloxy-5 β, 20-epoxy-1 beta-hydroxy-9-oxygen-7 β, 10 β-dimethoxy-11-yew alkene-13 α ester is that compound (1) is an important taxane compounds, in the multiple antineoplastic taxane hydride compounds of preparation and bulk drug, all has application.A kind of method of preparing this compound is disclosed in patent CN 1179776A, in the method by dimethyl sulphide intermediate at Raney Ni, under the condition of hydrogen and ethanol, reaction obtains after the crude product of compound (1), directly passes through the product that silica gel column chromatography (dichloromethane/ethyl acetate is moving phase) obtains compound (1).But applicant finds this preparation method and can produce a large amount of byproducts of reaction, and by conventional column chromatography and mesohigh preparative column, be all difficult to the separated of realization response by product and compound (1), thereby cause obtaining the compound (1) of higher degree.
The reaction equation that patent CN 1179776A mentions is as follows:
Summary of the invention
The object of the invention is to overcome above-mentioned weak point, provide a kind of simple to operate, be easy to 3-tertbutyloxycarbonyl-2-p-methoxyphenyl-4-phenyl-(2R of suitability for industrialized production, 4S, 5R)-1,3-oxazolidine-5-carboxylic acid 4 α-acetoxyl group-2 α-benzoyloxy-5 β, 20-epoxy-1 beta-hydroxy-9-oxygen-7 β, the process for purification of 10 β-dimethoxy-11-yew alkene-13 α ester.
According to technical scheme provided by the invention, a kind of method of dimethoxy bearing taxanes purification refine, step is as follows:
(1) preparation of primary product: get 3-tertbutyloxycarbonyl-2-p-methoxyphenyl-4-phenyl-(2R, 4S, 5R)-1,3-oxazolidine-5-carboxylic acid 4 α-acetoxyl group-2 α-benzoyloxy-5 β, 20-epoxy-1 beta-hydroxy-9-oxygen-7 β, the thick product of 10 β-dimethoxy-11-yew alkene-13 α ester, carry out silica gel column chromatography, use sherwood oil: 1: 10～10: 1 pairs of thick products of ethyl acetate carry out wash-out, collect elutriant, the concentrated primary product that obtains;
(2) preparation of pending product: add following any one agent combination in primary product, in the quality of primary product: 1. diacetyl oxide, Cerous chloride heptahydrate and tetrahydrofuran (THF); 2. 2,2,2-trichlorine ethoxy carbonyl chloride, pyridine and methylene dichloride; 3. methyl-sulphoxide, diacetyl oxide and acetic acid;-80～100 ℃ of stirring reaction 1-96h, by in the frozen water of reaction solution impouring 15～20 equivalents, the organic solvent that adds again 10～20 equivalents, fully stir 30～60min, isolate organic phase, with the saturated common salt moisture of 3000mL, clean organic phase 1-3 time, then use anhydrous sodium sulfate drying, under 30～40 ℃ of decompression 2.1～2.7kPa, be concentrated into after dry and obtain pending product;
(3) refinement treatment: by the pending product silica gel column chromatography of step (2) gained, the mixed solvent that uses petrol ether/ethyl acetate to form carries out wash-out, collection contains 3-tertbutyloxycarbonyl-2-p-methoxyphenyl-4-phenyl-(2R, 4S, 5R)-1,3-oxazolidine-5-carboxylic acid 4 α-acetoxyl group-2 α-benzoyloxy-5 β, 20-epoxy-1 beta-hydroxy-9-oxygen-7 β, the elutriant of 10 β-dimethoxy-11-yew alkene-13 α ester, is concentrated into the product dimethoxy bearing taxanes after dry being refined under 30～40 ℃ of decompression 2.1～2.7kPa.
In step (2), add the amount of reagent as follows, in the quality of step (1) gained primary product: 1. diacetyl oxide 0.1～10 equivalent, Cerous chloride heptahydrate 0.1～10 equivalent and tetrahydrofuran (THF) 5～15 equivalents; 2. 2,2,2-trichlorine ethoxy carbonyl chloride 0.1～10 equivalent, pyridine 0.2～20 equivalent and methylene dichloride 5～15 equivalents; Or 3. methyl-sulphoxide 0.1～100 equivalent, diacetyl oxide 0.1～100 equivalent and acetic acid 0.1～100 equivalent.
Described silicagel column is 400～800 orders.
In step (2), temperature of reaction is room temperature, and the reaction times is 22～26h.
In step (2), organic solvent is ethyl acetate or methylene dichloride.
The eluent components adopting during described silica gel column chromatography and ratio thereof are sherwood oil: ethyl acetate is 100: 1～1: 100.
Tool of the present invention has the following advantages: the invention provides a kind of 3-tertbutyloxycarbonyl-2-p-methoxyphenyl-4-phenyl-(2R, 4S, 5R)-1,3-oxazolidine-5-carboxylic acid 4 α-acetoxyl group-2 α-benzoyloxy-5 β, 20-epoxy-1 beta-hydroxy-9-oxygen-7 β, the process for purification refine of 10 β-dimethoxy-11-yew alkene-13 α ester, it is simple to operate, be easy to suitability for industrialized production, in reaction process, can not produce by product, improved reaction yield and product purity.
Accompanying drawing explanation
Product nuclear magnetic resonance map prepared by Fig. 1 the present invention.
Embodiment
Embodiment 1
30.0 grams of the thick products of the resulting product of preparation method (purity is 73.8%) of the compound (1) according to proposing in patent CN 1179776A are being equipped with to chromatography column (20 centimetres of the internal diameters of 1.2 kilograms of 400-800 order silica gel, high 80 centimetres) in carry out separation, the mixed solvent that uses petrol ether/ethyl acetate to form carries out wash-out, the elutriant that collection contains compound (1), 40 ℃ of decompressions (2.7KPa) are concentrated into the dry 12.0 grams of crude products that obtain, and purity is 89.4%.
Above-mentioned crude product is dropped in tetrahydrofuran (THF) (120mL), add diacetyl oxide (1.2mL), Cerous chloride heptahydrate (0.94g), after room temperature reaction 24 hours, in impouring frozen water (500mL), add ethyl acetate (200mL), fully stir 30 minutes.Isolate organic phase, saturated common salt washing (1000mL * 3), anhydrous sodium sulfate drying, 40 ℃ of decompressions (2.7KPa) are concentrated into dry slightly product.
Above-mentioned concentrated thick product is being equipped with to chromatography column (20 centimetres of the internal diameters of 0.8 kilogram of 400-800 order silica gel, high 80 centimetres) in carry out separation, the mixed solvent that uses petrol ether/ethyl acetate to form 1: 10 carries out wash-out, the elutriant that collection contains compound (1), 40 ℃ of decompressions (2.7KPa) are concentrated into the dry 11.2 grams of refined products that obtain, and purity is 94.5%.
Embodiment 2
30.0 grams of the thick products of the resulting product of preparation method (purity is 73.8%) of the compound (1) according to proposing in patent CN 1179776A are being equipped with to chromatography column (20 centimetres of the internal diameters of 1.2 kilograms of 400-800 order silica gel, high 80 centimetres) in carry out separation, the mixed solvent that uses petrol ether/ethyl acetate to form carries out wash-out, the elutriant that collection contains compound (1), 40 ℃ of decompressions (2.7KPa) are concentrated into the dry 12.0 grams of crude products that obtain, and purity is 89.4%.
Above-mentioned crude product is dropped in methylene dichloride (60mL), add pyridine (1.0mL), at 0 ℃, drip 2,2,2-trichlorine ethoxy carbonyl chloride (0.87mL), drips and finishes, after room temperature reaction 24 hours, in impouring frozen water (500mL), add methylene dichloride (400mL), fully stir 30 minutes.Isolate organic phase, saturated common salt washing (1000mL * 3), anhydrous sodium sulfate drying, 40 ℃ of decompressions (2.7KPa) are concentrated into dry slightly product.
Above-mentioned concentrated thick product is being equipped with to chromatography column (20 centimetres of the internal diameters of 0.8 kilogram of 400-800 order silica gel, high 80 centimetres) in carry out separation, the mixed solvent that uses petrol ether/ethyl acetate to form at 1: 100 carries out wash-out, the elutriant that collection contains compound (1), 40 ℃ of decompressions (2.7KPa) are concentrated into the dry 11.2 grams of refined products that obtain, and purity is 93.6%.
Embodiment 3
30.0 grams of the thick products of the resulting product of preparation method (purity is 73.8%) of the compound (1) according to proposing in patent CN 1179776A are being equipped with to chromatography column (20 centimetres of the internal diameters of 1.2 kilograms of 400-800 order silica gel, high 80 centimetres) in carry out separation, the mixed solvent that uses petrol ether/ethyl acetate to form carries out wash-out, the elutriant that collection contains compound (1), 40 ℃ of decompressions (2.7KPa) are concentrated into the dry 12.0 grams of crude products that obtain, and purity is 89.4%.
Above-mentioned crude product is dropped in methyl-sulphoxide (24.0mL), add diacetyl oxide (16.0mL), acetic acid (1.0mL), after room temperature reaction 96 hours, in impouring frozen water (1000mL), add ethyl acetate (800mL), fully stir 30 minutes.Isolate organic phase, saturated sodium bicarbonate aqueous solution is washed (1000mL * 3), saturated common salt washing (1000mL * 3), and anhydrous sodium sulfate drying, 40 ℃ of decompressions (2.7KPa) are concentrated into dry slightly product.
Above-mentioned concentrated thick product is being equipped with to chromatography column (20 centimetres of the internal diameters of 0.8 kilogram of 400-800 order silica gel, high 80 centimetres) in carry out separation, the mixed solvent that uses petrol ether/ethyl acetate to form at 100: 1 carries out wash-out, the elutriant that collection contains compound (1), 40 ℃ of decompressions (2.7KPa) are concentrated into the dry 11.2 grams of refined products that obtain, and purity is 92.8%.
Get embodiment 3 products and carry out nucleus magnetic resonance.
Be illustrated in figure 1 product nuclear magnetic resonance spectrum
1h-NMR (400MHz:CDCl
3; Chemical shift δ ppm; Coupling constant J Hz)
1.03(s，9H)；1.07(s，3H)；1.19(s，3H)；1.51(s，3H)；1.68(s，3H)；1.82(dd，J＝15.9，1H)；1.89(s，3H)；2.09(m，2H)；2.65(dd，J＝15.9，1H)；3.25(s，3H)；3.39(s，3H)；3.83(d，J＝7，1H)；3.83(s，3H)；4.12(d，J＝8，1H)；4.26(d，J＝8，1H)；4.55(d，J＝8，1H)；4.70(s，1H)；4.88(d，J＝12，1H)；5.40(bs，1H)；5.60(d，J＝12，1H)；6.12(t，J＝10，1H)；6.39(bs，1H)；6.91(d，J＝10，2H)；7.38-7.64(mt，10H)；8.03(d，J＝10，2H)
Claims (5)
1. a method for dimethoxy bearing taxanes purification refine, is characterized in that step is as follows:
(1) preparation of primary product: get 3-tertbutyloxycarbonyl-2-p-methoxyphenyl-4-phenyl-(2
r, 4
s, 5
r)-1,3-oxazolidine-5-carboxylic acid 4 α-acetoxyl group-2 α-benzoyloxy-5 β, 20-epoxy-1 beta-hydroxy-9-oxygen-7 β, the thick product of 10 β-dimethoxy-11-yew alkene-13 α ester, carry out silica gel column chromatography, use sherwood oil and eluent ethyl acetate liquid to carry out wash-out to thick product, collect elutriant, the concentrated primary product that obtains;
(2) preparation of pending product: add following any one agent combination in primary product, in the quality of primary product: 1. diacetyl oxide, Cerous chloride heptahydrate and tetrahydrofuran (THF); 2. 2,2,2-trichlorine ethoxy carbonyl chloride, pyridine and methylene dichloride; 3. methyl-sulphoxide, diacetyl oxide and acetic acid;-80 ~ 100 ℃ of stirring reaction 1-96h, by in the frozen water of reaction solution impouring 15 ~ 20 equivalents, the organic solvent that adds again 10 ~ 20 equivalents, fully stir 30 ~ 60min, isolate organic phase, with the saturated common salt moisture of 3000mL, clean organic phase 1-3 time, then use anhydrous sodium sulfate drying, under 30 ~ 40 ℃ of decompression 2.1 ~ 2.7kPa, be concentrated into after dry and obtain pending product;
(3) refinement treatment: by the pending product silica gel column chromatography of step (2) gained, the mixed solvent that uses petrol ether/ethyl acetate to form carries out wash-out, collects and contains 3-tertbutyloxycarbonyl-2-p-methoxyphenyl-4-phenyl-(2
r, 4
s, 5
r)-1,3-oxazolidine-5-carboxylic acid 4 α-acetoxyl group-2 α-benzoyloxy-5 β, 20-epoxy-1 beta-hydroxy-9-oxygen-7 β, the elutriant of 10 β-dimethoxy-11-yew alkene-13 α ester, is concentrated into the product dimethoxy bearing taxanes after dry being refined under 30 ~ 40 ℃ of decompression 2.1 ~ 2.7kPa;
In step (2), add the amount of reagent as follows, in the quality of step (1) gained primary product: 1. diacetyl oxide 0.1 ~ 10 equivalent, Cerous chloride heptahydrate 0.1 ~ 10 equivalent and tetrahydrofuran (THF) 5 ~ 15 equivalents; 2. 2,2,2-trichlorine ethoxy carbonyl chloride 0.1 ~ 10 equivalent, pyridine 0.2 ~ 20 equivalent and methylene dichloride 5 ~ 15 equivalents; 3. methyl-sulphoxide 0.1 ~ 100 equivalent, diacetyl oxide 0.1 ~ 100 equivalent and acetic acid 0.1 ~ 100 equivalent.
2. the method for dimethoxy bearing taxanes purification refine according to claim 1, is characterized in that: described silicagel column is 400 ~ 800 orders.
3. the method for dimethoxy bearing taxanes purification refine according to claim 1, is characterized in that: in step (2), temperature of reaction is room temperature, and the reaction times is 22 ~ 26h.
4. the method for dimethoxy bearing taxanes purification refine according to claim 1, is characterized in that: in step (2), organic solvent is ethyl acetate or methylene dichloride.
5. the method for dimethoxy bearing taxanes purification refine according to claim 1, is characterized in that: the eluent components adopting during described silica gel column chromatography and ratio thereof are sherwood oil: ethyl acetate is 100:1 ~ 1:100.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210038631.3A CN102603724B (en) | 2011-10-20 | 2012-02-20 | Method for purifying and refining dimethoxy taxane compound |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110322882.X | 2011-10-20 | ||
| CN201110322882 | 2011-10-20 | ||
| CN201210038631.3A CN102603724B (en) | 2011-10-20 | 2012-02-20 | Method for purifying and refining dimethoxy taxane compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102603724A CN102603724A (en) | 2012-07-25 |
| CN102603724B true CN102603724B (en) | 2014-02-26 |
Family
ID=46521554
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210038631.3A Active CN102603724B (en) | 2011-10-20 | 2012-02-20 | Method for purifying and refining dimethoxy taxane compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102603724B (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1179776A (en) * | 1995-03-27 | 1998-04-22 | 罗纳-布朗克罗莱尔股份有限公司 | Novel taxoids, preparation thereof and pharmaceutical compositions containing same |
| CN1944435A (en) * | 2006-10-19 | 2007-04-11 | 上海大学 | New 4-substituent-1-dehydroxy baccatin VI derivative and its preparing method |
| CN102093315A (en) * | 2010-12-23 | 2011-06-15 | 上海大学 | C7 and C10 modified 1-dehydroxyl taxol analogue and preparation method thereof |
-
2012
- 2012-02-20 CN CN201210038631.3A patent/CN102603724B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1179776A (en) * | 1995-03-27 | 1998-04-22 | 罗纳-布朗克罗莱尔股份有限公司 | Novel taxoids, preparation thereof and pharmaceutical compositions containing same |
| CN1944435A (en) * | 2006-10-19 | 2007-04-11 | 上海大学 | New 4-substituent-1-dehydroxy baccatin VI derivative and its preparing method |
| CN102093315A (en) * | 2010-12-23 | 2011-06-15 | 上海大学 | C7 and C10 modified 1-dehydroxyl taxol analogue and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102603724A (en) | 2012-07-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111944006A (en) | New 7-keto-6 beta-alkyl cholanic acid derivative in preparation of obeticholic acid and application thereof in medical field | |
| CN102603724B (en) | Method for purifying and refining dimethoxy taxane compound | |
| CN106256833B (en) | The method for preparing 3,7- bis- (trimethyl silicon substrate oxygroup) -5 β of -6- alkene-cholane -24- acid methyl esters | |
| EP2872477B1 (en) | Process for the preparation of ingenol-3-angelate from 20-deoxy-ingenol | |
| CN103402973B (en) | Compound and production method thereof, and for the production of the method for Ro 64-0796/002 | |
| CN107641080B (en) | A kind of dihydronaphthalene ketones derivant and preparation method thereof containing spirane structure | |
| CN106117222A (en) | Benzophenanthrene dodecyloxy bridging isobutyltrimethylmethane. phenyl porphyrin binary compound discotic mesogenic material synthesis method | |
| CN108314641B (en) | Preparation method of natural product Norpsilocin | |
| Satake et al. | Scalable synthesis of a new dihydroxylated intermediate for tetrodotoxin and its analogues | |
| CN106117220A (en) | The synthetic method of benzophenanthrene dodecyloxy bridging isobutyltrimethylmethane. phenyl porphyrin metal Zn coordination compound | |
| CN106905358B (en) | Preparation of vitamin D3Process for preparing analogue intermediates | |
| CN108299297A (en) | A kind of novel 6- alkyl phenanthridines and derivative and preparation method thereof | |
| CN105017268A (en) | 2-tertbutyloxycarbonyl-7-carbonyl-5-O-2-azaspiro(3.4)octane synthesis method | |
| Setterholm et al. | Sequential exo-mode oxacyclizations for the synthesis of the CD substructure of brevenal | |
| CN106905308B (en) | A kind of thia cup [4] arene derivatives and preparation method thereof | |
| CN105884706A (en) | Cetilistat efficient synthesizing method | |
| Betz et al. | Preparation of Highly Hindered Polyenes with tert‐Butyl Groups in Internal Positions | |
| CN107200770B (en) | In the synthesis of special plast ketone eposide isomers efficiently separate and circulation utilization method | |
| CN107628919A (en) | A kind of method of synthesis β halogen formate esters compounds | |
| CN109970643A (en) | A kind of green synthesis method of the Activities of Tetrahydroacridine Derivatives under the promotion of iodine anion | |
| CN106349073B (en) | A kind of synthetic method of phenacylidene malonic acid ester type compound | |
| CN109486866A (en) | The method that biocatalysis prepares (S) -4- decyl alcohol | |
| CN103044448B (en) | A kind of synthetic method of Tazobactam Sodium | |
| CN108840881A (en) | A kind of tetra- substituted benzene of 1,2,3,5- and its synthetic method of the silicon substrate containing 3- | |
| CN102260236A (en) | Preparation method of coumarin compounds |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C53 | Correction of patent of invention or patent application | ||
| CB02 | Change of applicant information |
Address after: 214199 Xishan City, Jiangsu Province, Donggang Town, Hong Kong under the red bean Group Co., Ltd. Applicant after: JIANGSU YEW BIOTECHNOLOGY CO.,LTD. Address before: 214199 Xishan City, Jiangsu Province, Donggang Town, Hong Kong under the red bean Group Co., Ltd. Applicant before: JIANGSU YEW BIOTECHNOLOGY Co.,Ltd. |
|
| COR | Change of bibliographic data |
Free format text: CORRECT: APPLICANT; FROM: JIANGSU YEW BIOTECHNOLOGY CO., LTD. TO: JIANGSU YEW BIOTECHNOLOGY CO., LTD. |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CP01 | Change in the name or title of a patent holder | ||
| CP01 | Change in the name or title of a patent holder |
Address after: 214199 Jiangsu Wuxi Xishan District Donggang Town Hong Kong Red Group Co., Ltd. Patentee after: JIANGSU YEW HEALTH TECHNOLOGY CO.,LTD. Address before: 214199 Jiangsu Wuxi Xishan District Donggang Town Hong Kong Red Group Co., Ltd. Patentee before: JIANGSU YEW BIOTECHNOLOGY CO.,LTD. |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20220819 Address after: 214199 No. 111, Qinxin Road, Donggang Town, Xishan District, Wuxi City, Jiangsu Province Patentee after: Wuxi yew Pharmaceutical Co.,Ltd. Address before: 214199 Jiangsu Wuxi Xishan District Donggang Town Hong Kong Red Group Co., Ltd. Patentee before: JIANGSU YEW HEALTH TECHNOLOGY CO.,LTD. |