CN102633658B - Method for resolving 3-amino-3-phenylpropanol - Google Patents
Method for resolving 3-amino-3-phenylpropanol Download PDFInfo
- Publication number
- CN102633658B CN102633658B CN201110038696.3A CN201110038696A CN102633658B CN 102633658 B CN102633658 B CN 102633658B CN 201110038696 A CN201110038696 A CN 201110038696A CN 102633658 B CN102633658 B CN 102633658B
- Authority
- CN
- China
- Prior art keywords
- amino
- phenylpropyl alcohol
- proline
- tolysulfonyl
- splits
- 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
Landscapes
- Pyrrole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a method for resolving 3-amino-3-phenylpropanol. Tolylsulfonyl proline is used as a resolving agent to effectively resolve S-3-amino-3-phenylpropanol and R-3-amino-3-phenylpropanol. Compared with the prior art, the invention has the advantage of reasonable technique, and is simple to operate; the resolving agent is prepared from cheap and accessible proline; the obtained product has high optical purity and chemical purity; and thus, the invention is suitable for industrialized large-scale production of chiral 3-amino-3-phenylpropanol.
Description
Technical field
The present invention relates to the production of a kind of chirality 3-amino-3-phenylpropyl alcohol, especially relate to the method for a kind of 3-of fractionation amino-3-phenylpropyl alcohol.
Background technology
Chirality 3-amino-3-phenylpropyl alcohol is a kind of important medicine intermediate, particularly S-3-amino-3-phenylpropyl alcohol (1) is the key intermediate of multiple chiral drug, can be for the synthesis of dapoxetine (Dapoxetine) (2), anti-Chinese mugwort new drug Selzentry's (Maraviroc) (3) is synthetic. and dapoxetine is that the first goes through to treat the oral medicine (tablet) of the type of premature ejaculation in the world, Johson & Johnson is at present in Europe Finland, and the states such as Sweden, Portugal, Austria, Italy, Spain obtain and examine listing. and the synthetic method of dapoxetine is as follows:
Synthetic key is to solve chiral intermediate S-3-amino-3-phenylpropyl alcohol, and the main synthetic method of S-3-amino-3-phenylpropyl alcohol has at present; 1) by S-3-amino-reduction of 3-phenylpropionic acid obtains, and S-3-amino-3-phenylpropionic acid needs enzyme to split or asymmetry catalysis is synthetic, and cost of material is expensive, and cost is high.2) by some specific enzyme catalysis, as the people such as Nitin W.Fadnavis adopt, immobilized penicillin G acylase splits that (Tetrahedron:Asymmetry 17,2006,240-244), the people such as Oliver Torre adopt the Lipase fractionation, and (Tetrahedron:Asymmetry 17,2006,860-866) these methods or enzyme are rareer, expensive, split effect EE value not high, difficult suitability for industrialized production.3) by the chirality asymmetric synthesis, as the people such as Shafi A. start the 2PHAL by (DHQ) from methyl cinnamate, OsO4, asymmetric oxidation synthesize, (Tetrahedron:Asymmetry 18,2007,2099-2103), the people such as Pinak M.Chincholkar start to be synthesized to the 3-hydroxy azetidin-2-one compound of chirality from the L-TARTARIC ACID diethyl ester, restore open loop and obtain S-3-amino-3-phenylpropyl alcohol, (Tetrahedron 65,2009,2605-2609) more than synthesis step is all wanted the 7-8 step, be difficult to amplify and produce.Consider that 3-amino-3-phenylpropyl alcohol ratio is easier to preparation, cost is low, and we adopt chemical method to take the tolysulfonyl proline(Pro) and 3-amino-3-phenylpropyl alcohol are directly split as resolving agent, obtained more satisfactory effect, chirality can reach more than 98%, simple to operate, is convenient to suitability for industrialized production.
Summary of the invention
Purpose of the present invention is exactly to provide a kind of technique simple in order to overcome the defect that above-mentioned prior art exists, and cost is lower, the method for the fractionation 3-amino that can recycle-3-phenylpropyl alcohol.
Purpose of the present invention can be achieved through the following technical solutions:
A kind of method that splits 3-amino-3-phenylpropyl alcohol is characterized in that the method be take the tolysulfonyl proline(Pro) as resolving agent, and 3-amino-3-phenylpropyl alcohol is split and obtains S-3-amino-3-phenylpropyl alcohol or R-3-amino-3-phenylpropyl alcohol.
The method concrete steps comprise: controlling temperature is 0～25 ℃, by 3-amino-3-phenylpropyl alcohol and tolysulfonyl proline(Pro), be 3 by weight: (4～5) are uniformly mixed 2～6h in mixed organic solvents, standing 12～48h again, then use the mixed organic solvents recrystallizing and refining three times, the purified salt obtained is stirring and dissolving in HCl at room temperature, utilize ethyl acetate rinse, the gained water utilizes NaOH solution to regulate pH value to be dry after the ethyl acetate extraction, decolouring again after 12, to concentrate the 3-amino after being split-3-phenylpropyl alcohol.
Described tolysulfonyl proline(Pro) is tolysulfonyl-L-PROLINE (Tos-L-Pro-OH) or tolysulfonyl-D-PROLINE (Tos-D-Pro-OH).
Described tolysulfonyl-L-PROLINE splits and obtains S-3-amino-3-phenylpropyl alcohol 3-amino-3-phenylpropyl alcohol.
Described tolysulfonyl-D-PROLINE splits and obtains R-3-amino-3-phenylpropyl alcohol 3-amino-3-phenylpropyl alcohol.
Described mixed organic solvents is that ethyl acetate and alcohols are (1～4) by volume: 1 mixed solvent formed.
Described alcohols comprises methyl alcohol, ethanol or Virahol.
The equivalent concentration of described HCl is 6N.
The equivalent concentration of described NaOH solution is 4N.
Compared with prior art, resolving agent of the present invention, cheap and easy to get, form good crystal with 3-amino-3-phenylpropyl alcohol, can obtain the product of optical purity more than 98% through three recrystallizations, and resolving agent can be recycled, simple to operate, be easy to suitability for industrialized production.
Embodiment
Below in conjunction with specific embodiment, the present invention is described in detail.
Embodiment 1
Synthesizing of tolysulfonyl-L-PROLINE
448 gram L-PROLINEs, be dissolved in 6.5 premium on currency, adds sodium carbonate 1041 grams, at 0 degree, then adds Tosyl chloride 1071 grams, room temperature reaction 4 hours, and the concentrated hydrochloric acid acidifying, filter, and washing, obtain tolylsulfonyl-L-PROLINE 936 grams, fusing point: 41-43 ℃.
Embodiment 2
Synthesizing of tolysulfonyl-D-PROLINE
448 gram D-PROLINEs, according to embodiment 1, obtain tolylsulfonyl-D-PROLINE 895 grams.Fusing point: 40-42 ℃.
Embodiment 3
Synthesizing of amino-3 phenylpropyl alcohols of DL-3-
In the 10L tetrahydrofuran (THF), add 1 kilogram of 3-amino-3 phenylpropionic acid and sodium borohydride 250 grams, below 0 degree, drip 550 milliliters, approximately within 4 hours, add, stirred overnight at room temperature, drip methyl alcohol 1L, then concentrate and remove solvent, add 4N NaOH 10L reflux 6 hours, cooling use dichloromethane extraction three times, combined dichloromethane is dry mutually, crystallization, obtain DL-3-amino-3 phenylpropyl alcohol 635 grams.Fusing point: 70-74 ℃, 1HNMR (CDCl3): 7.37-7.22 (m, 5H), 4.11 (t, 1H), 3.78 (t, 2H), 2.77 (br s, 3H), 1.92-1.85 (m, 2H).
Embodiment 4
Synthesizing of S-3-amino-3-phenylpropyl alcohol
Amino-3 phenylpropyl alcohol 15 grams of DL-3-, and tolysulfonyl-D-PROLINE 25 grams stir 2 hours in 10 milliliters of 200 milliliters of ethyl acetates and methyl alcohol, then static 0 degree is placed 24 hours, then filter, obtain amino-3 phenylpropyl alcohol tosilate of crude product S-3-, then use ethyl acetate: methyl alcohol=4: 1 (volume ratio) recrystallization 3 times, obtaining amino-3 phenylpropyl alcohol tolysulfonyl of finished product S-3--D-PROLINE salt 11g. joins upper gained refined salt in the HCL of 100 milliliters of 6N, stirring and dissolving is after room temperature, by ethyl acetate, wash three times, water is adjusted PH to 12 with 4N NaOH, with ethyl acetate extraction three times, merge the ethyl acetate phase, dry, decolouring, concentrated S-3-amino-3-phenylpropyl alcohol is 2.1 grams approximately, faint yellow oily matter.Optically-active: [a] 20/D-22 ° (c=1 in CHCl3).1H?NMR(CDCl3)7.38-7.15(5H，m)，3.86(1H，t)，3.69-3.63(2H，m)，2.32-1.77(2H，m)。
Embodiment 5
Amino-3 phenylpropyl alcohol 15 grams of DL-3-, and tolysulfonyl-D-PROLINE 25 grams stir 2 hours in 15 milliliters of 200 milliliters of ethyl acetates and ethanol, then static 0 degree is placed 12 hours, then filter, obtain amino-3 phenylpropyl alcohol tosilate of crude product S-3-, then use ethyl acetate: ethanol=3: 1 (volume ratio) recrystallization 3 times obtains amino-3 phenylpropyl alcohol tolysulfonyl of finished product S-3--D-PROLINE salt 10g.Upper gained refined salt is joined in the HCL of 100 milliliters of 6N, stirring and dissolving is after room temperature, by ethyl acetate, wash three times, water is adjusted PH to 12 with 4N NaOH, with ethyl acetate extraction three times, merges the ethyl acetate phase, dry, decolouring, concentrated S-3-amino-3-phenylpropyl alcohol is 1.9 grams approximately, faint yellow oily matter.Optically-active: [a] 20/D-25 ° (c=1 in CHCl3).1H?NMR(CDCl3)7.38-7.15(5H，m)，3.86(1H，t)，3.69-3.63(2H，m)，2.32-1.77(2H，m)。
Embodiment 6
Amino-3 phenylpropyl alcohol 15 grams of DL-3-, and tolysulfonyl-D-PROLINE 25 grams stir 4 hours in 20 milliliters of 200 milliliters of ethyl acetates and Virahols, then static 25 degree are placed 48 hours, then filter, obtain amino-3 phenylpropyl alcohol tosilate of crude product S-3-, then use ethyl acetate: Virahol=2: 1 (volume ratio) recrystallization 3 times obtains amino-3 phenylpropyl alcohol tolysulfonyl of finished product S-3--D-PROLINE salt 12g.Upper gained refined salt is joined in the HCL of 100 milliliters of 6N, stirring and dissolving is after room temperature, by ethyl acetate, wash three times, water is adjusted PH to 12 with 4N NaOH, with ethyl acetate extraction three times, merges the ethyl acetate phase, dry, decolouring, concentrated S-3-amino-3-phenylpropyl alcohol is 2.3 grams approximately, faint yellow oily matter.Optically-active: [a] 20/D-23 ° (c=1 in CHCl3).1H?NMR(CDCl3)7.38-7.15(5H，m)，3.86(1H，t)，3.69-3.63(2H，m)，2.32-1.77(2H，m)。
Embodiment 7
Amino-3 phenylpropyl alcohol 500g of DL-3-, and tolysulfonyl-D-PROLINE 815G stirs 6 hours in 300 milliliters of ethyl acetate 5L and ethanol, then static 0 degree is placed 24 hours, then filter, obtain amino-3 phenylpropyl alcohol tosilate of crude product S-3-, then use ethyl acetate: ethanol=3: 1 (volume ratio) recrystallization 3 times, obtaining amino-3 phenylpropyl alcohol tolysulfonyl of finished product S-3--D-PROLINE salt 433g. joins upper gained refined salt in the HCL of 600 milliliters of 6N, stirring and dissolving is after room temperature, first add 700 milliliters of ethyl acetate extractions once, again with 300 milliliters of ethyl acetate extractions once, merge organic phase, use 1NHCL, wash twice, merge organic phase, dry, concentrated, pour sherwood oil and must reclaim tolysulfonyl-D-PROLINE, merge the sour water phase, adjust PH to 12 with 4N NaOH, with ethyl acetate extraction three times, merge the ethyl acetate phase, dry, decolouring, concentrate to obtain S-3-amino-about 90G of 3-phenylpropyl alcohol, faint yellow oily matter.Optically-active: [a] 20/D-24 ° (c=1 in CHCl3).1H?NMR(CDCl3)7.38-7.15(5H，m)，3.86(1H，t)，3.69-3.63(2H，m)，2.32-1.77(2H，m)。
Embodiment 8
Synthesizing of R-3-amino-3-phenylpropyl alcohol
Amino-3 phenylpropyl alcohol 30g of DL-3-, and tolysulfonyl-L-PROLINE 49G stirs 3 hours in 20 milliliters of 300 milliliters of ethyl acetates and methyl alcohol, then static 0 degree is placed 24 hours, then filter, obtain amino-3 phenylpropyl alcohol tosilate of crude product R-3-, then use ethyl acetate: methyl alcohol=4: 1 (volume ratio) recrystallization 3 times, obtaining amino-3 phenylpropyl alcohol tolysulfonyl of finished product S-3--D-PROLINE salt 25g. joins upper gained refined salt in the HCL of 100 milliliters of 6N, stirring and dissolving is after room temperature, ethyl acetate washing three times, water, adjust PH to 12 with 4N NaOH, with ethyl acetate extraction three times, merge the ethyl acetate phase, dry, decolouring, concentrate to obtain R-3-amino-about 5.2G of 3-phenylpropyl alcohol, faint yellow oily matter.Optically-active: [a] 20/D+24 ° (c=1 in CHCl3).1H?NMR(CDCl3)7.38-7.16(5H，m)，3.86(1H，t)，3.69-3.64(2H，m)，2.32-1.78(2H，m)。
Embodiment 9
A kind of method that splits 3-amino-3-phenylpropyl alcohol, it is resolving agent that the method be take tolysulfonyl-L-PROLINE (Tos-L-Pro-OH), and 3-amino-3-phenylpropyl alcohol is split and obtains S-3-amino-3-phenylpropyl alcohol.Concrete steps comprise: controlling temperature is 0 ℃, by 3-amino-3-phenylpropyl alcohol and tolysulfonyl-L-PROLINE (Tos-L-Pro-OH) be by weight 3: 4 at ethyl acetate and methyl alcohol, be to be uniformly mixed 2h in forming mixed organic solvents at 1: 1 by volume, standing 12h again, then use this mixed organic solvents recrystallizing and refining three times, stirring and dissolving in the HCl that the purified salt obtained is at room temperature 6N in equivalent concentration, utilize ethyl acetate rinse, it is drying after the ethyl acetate extraction again after 12 that the gained water utilizes NaOH solution that equivalent concentration is 4N to regulate pH value, decolouring, concentrated, fractionation obtains S-3-amino-3-phenylpropyl alcohol.
Embodiment 10
A kind of method that splits 3-amino-3-phenylpropyl alcohol, it is resolving agent that the method be take tolysulfonyl-D-PROLINE (Tos-D-Pro-OH), and 3-amino-3-phenylpropyl alcohol is split and obtains R-3-amino-3-phenylpropyl alcohol.Concrete steps comprise: controlling temperature is 25 ℃, by 3-amino-3-phenylpropyl alcohol and tolysulfonyl-D-PROLINE (Tos-D-Pro-OH) be by weight 3: 5 at ethyl acetate and Virahol, be to be uniformly mixed 6h in forming mixed organic solvents at 1: 4 by volume, standing 48h again, then use this mixed organic solvents recrystallizing and refining three times, stirring and dissolving in the HCl that the purified salt obtained is at room temperature 6N in equivalent concentration, utilize ethyl acetate rinse, it is drying after the ethyl acetate extraction again after 12 that the gained water utilizes NaOH solution that equivalent concentration is 4N to regulate pH value, decolouring, concentrated, fractionation obtains R-3-amino-3-phenylpropyl alcohol.
Claims (7)
1. a method that splits 3-amino-3-phenylpropyl alcohol, it is characterized in that, the method be take the tolysulfonyl proline(Pro) as resolving agent, 3-amino-3-phenylpropyl alcohol is split and obtains S-3-amino-3-phenylpropyl alcohol or R-3-amino-3-phenylpropyl alcohol, the method concrete steps comprise: controlling temperature is 0～25 ℃, by 3-amino-3-phenylpropyl alcohol and tolysulfonyl proline(Pro), be that 3 ︰ (4～5) are uniformly mixed 2～6h in mixed organic solvents by weight, standing 12～48h again, then use the mixed organic solvents recrystallizing and refining three times, the purified salt obtained is stirring and dissolving in HCl solution at room temperature, utilize ethyl acetate rinse, it is drying after the ethyl acetate extraction again after 12 that the gained water utilizes NaOH solution to regulate pH value, decolouring, concentrated, the 3-amino after being split-3-phenylpropyl alcohol, described tolysulfonyl proline(Pro) is tolysulfonyl-L-PROLINE (Tos-L-Pro-OH) or tolysulfonyl-D-PROLINE (Tos-D-Pro-OH).
2. a kind of method that splits 3-amino-3-phenylpropyl alcohol according to claim 1, is characterized in that, described tolysulfonyl-L-PROLINE splits and obtains S-3-amino-3-phenylpropyl alcohol 3-amino-3-phenylpropyl alcohol.
3. a kind of method that splits 3-amino-3-phenylpropyl alcohol according to claim 1, is characterized in that, described tolysulfonyl-D-PROLINE splits and obtains R-3-amino-3-phenylpropyl alcohol 3-amino-3-phenylpropyl alcohol.
4. a kind of method that splits 3-amino-3-phenylpropyl alcohol according to claim 1, is characterized in that, described mixed organic solvents is that ethyl acetate and alcohols are the (mixed solvent that 1～4) ︰ 1 forms by volume.
5. a kind of method that splits 3-amino-3-phenylpropyl alcohol according to claim 4, is characterized in that, described alcohols comprises methyl alcohol, ethanol or Virahol.
6. a kind of method that splits 3-amino-3-phenylpropyl alcohol according to claim 1, is characterized in that, the equivalent concentration of described HCl solution is 6N.
7. a kind of method that splits 3-amino-3-phenylpropyl alcohol according to claim 1, is characterized in that, the equivalent concentration of described NaOH solution is 4N.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110038696.3A CN102633658B (en) | 2011-02-15 | 2011-02-15 | Method for resolving 3-amino-3-phenylpropanol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110038696.3A CN102633658B (en) | 2011-02-15 | 2011-02-15 | Method for resolving 3-amino-3-phenylpropanol |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102633658A CN102633658A (en) | 2012-08-15 |
| CN102633658B true CN102633658B (en) | 2014-01-08 |
Family
ID=46618257
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201110038696.3A Active CN102633658B (en) | 2011-02-15 | 2011-02-15 | Method for resolving 3-amino-3-phenylpropanol |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102633658B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111499524B (en) * | 2019-01-30 | 2023-02-07 | 哈尔滨工业大学（深圳） | Method for preparing amino alcohol compound by using halogenated intermediate |
| CN113877543A (en) * | 2021-11-03 | 2022-01-04 | 上海工程技术大学 | Chiral metal organic framework functionalized composite material and preparation method and application thereof |
-
2011
- 2011-02-15 CN CN201110038696.3A patent/CN102633658B/en active Active
Non-Patent Citations (6)
| Title |
|---|
| An efficient formal synthesis of (S)-dapoxetine from enantiopure 3-hydroxy azetidin-2-one;Pinak M. Chincholkar et al.;《Tetrahedron》;20081124;第65卷;2605–2609 * |
| Lipase-catalyzed resolution of chiral 1,3-amino alcohols:application in the asymmetric synthesis of (S)-dapoxetine;Oliver Torre et al.;《Tetrahedron: Asymmetry》;20060323;第17卷;860–866 * |
| Nitin W. Fadnavis et al..Preparation of enantiomerically pure (R)- and (S)-3-amino-3-phenyl-1-propanol via resolution with immobilized penicillin G acylase.《Tetrahedron: Asymmetry》.2006,第17卷240–244. |
| OliverTorreetal..Lipase-catalyzedresolutionofchiral1 3-amino alcohols:application in the asymmetric synthesis of (S)-dapoxetine.《Tetrahedron: Asymmetry》.2006 |
| Pinak M. Chincholkar et al..An efficient formal synthesis of (S)-dapoxetine from enantiopure 3-hydroxy azetidin-2-one.《Tetrahedron》.2008,第65卷2605–2609. |
| Preparation of enantiomerically pure (R)- and (S)-3-amino-3-phenyl-1-propanol via resolution with immobilized penicillin G acylase;Nitin W. Fadnavis et al.;《Tetrahedron: Asymmetry》;20060123;第17卷;240–244 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102633658A (en) | 2012-08-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103333942B (en) | A synthetic method for (R)-praziquantel | |
| CN114014787B (en) | Asymmetric synthesis method for preparing (2S,3R) -p-methylsulfonylphenylserine ethyl ester | |
| CN103265528B (en) | Esomeprazole magnesium preparation method | |
| CN103193779B (en) | A kind of preparation method of Lunesta | |
| CN100591649C (en) | Method of preparing R-(+)-3-chlorophenylpropanol | |
| CN102633658B (en) | Method for resolving 3-amino-3-phenylpropanol | |
| CN104478746B (en) | A kind of preparation method of DL-Lys | |
| WO2016045416A1 (en) | Intermediate for use in synthesizing paroxetine, preparation method for the intermediate, and uses thereof | |
| CN104231033A (en) | Preparation method of dutasteride | |
| CN110642790B (en) | Preparation method of rosuvastatin calcium and intermediate thereof | |
| CN101875615A (en) | Method for preparing tert-leucine with high selectivity | |
| CN105745191B (en) | A kind of preparation method of silodosin and its intermediate | |
| CN101239983A (en) | Chiral synthesis method for (-)-galantamin hydrobromide | |
| CN113336764B (en) | Bipyridine ligand with axial chirality and synthetic method thereof | |
| CN106928149A (en) | A kind of preparation method of olaparib | |
| CN112679407B (en) | Preparation method of chiral 5-substituted proline compound | |
| CN105585511B (en) | (R) preparation method of N tertbutyloxycarbonyls biphenyl Propanolamine | |
| CN104370953B (en) | (R)-tert-butyl dimethyl siloxy-glutaric acid monoester preparation method | |
| CN102391140B (en) | Preparation method of N-(2- indanyl) amino acid alkyl ester | |
| CN106883192A (en) | The synthetic method of the benzoic acid derivative of nitrogenous class heterocyclic antineoplastic pharmaceutical actives oxazolyl modification | |
| CN107383137A (en) | A kind of synthetic method of chenodeoxycholic acid | |
| CN111087402B (en) | Method for asymmetrically synthesizing Epicocin G alkaloid of ETP natural product | |
| CN103224489B (en) | Method for enhancing production yield and rate of esomeprazole | |
| CN109574984A (en) | Synthesize the new method of hydrosulphuric acid clopidogrel and its intermediate | |
| CN104262201A (en) | Synthesis method of chiral optically-pure (S)-3-aminovaleric acid |
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 | ||
| CP01 | Change in the name or title of a patent holder | ||
| CP01 | Change in the name or title of a patent holder |
Address after: 201512 Jinshan Qiushi Road No. 688 building 4 208-213 Patentee after: SHANGHAI YULI BIOTECHNOLOGY CO.,LTD. Address before: 201512 Jinshan Qiushi Road No. 688 building 4 208-213 Patentee before: Shanghai Yuli Biotechnology Co.,Ltd. |
|
| CP03 | Change of name, title or address | ||
| CP03 | Change of name, title or address |
Address after: 201512 Jinshan Qiushi Road No. 688 building 4 208-213 Patentee after: Shanghai Yuli Biotechnology Co.,Ltd. Address before: 201512 Shanghai city Jinshan District Qiushi Road No. 688 Building No. 4 room 208 Patentee before: SHANGHAI YURLIC CHEMICAL S&T Co.,Ltd. |