CN102286004A - Method for preparing latamoxef sodium intermediate - Google Patents
Method for preparing latamoxef sodium intermediate Download PDFInfo
- Publication number
- CN102286004A CN102286004A CN2011102812908A CN201110281290A CN102286004A CN 102286004 A CN102286004 A CN 102286004A CN 2011102812908 A CN2011102812908 A CN 2011102812908A CN 201110281290 A CN201110281290 A CN 201110281290A CN 102286004 A CN102286004 A CN 102286004A
- Authority
- CN
- China
- Prior art keywords
- oxo
- solvent
- benzhydryl ester
- acid benzhydryl
- benzamide
- 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.)
- Pending
Links
Abstract
The invention discloses a method for preparing a latamoxef sodium intermediate. The method comprising the following steps of: adding 6-beta-benzamide-4-oxo-penicillanate and triphenylphosphine to benzene and alkane solvents to react under a backflow; and decompressing, concentrating, adding acetonitrile and alcohol solvents to the concentrated objects, crystallizing, filtering, concentrating, cooling, devitrifying, filter and obtaining the latamoxef sodium intermediate. The triphenylphosphine is selected to replace tributyl phosphine with toxicity damage, and a dehydration device not easy to be controlled is cancelled, thus the production equipment is simplified; the prepared side product-triphenylphosphine sulfide in a mixing system of the acetonitrile and alcohol solvents can be crystallized in solid form, thus the followed impurity removal process is reduced, the production quality is beneficial to being ensured and the yield is beneficial to being increased. The product yield can be increased from 40% in the original technique to 58%, the material cost can be reduced by about 600yuan/Kg, the technical conditions are provided for scale production of oxacephem nucleus, the economic benefit is remarkable, and the market competitive powder is stronger.
Description
Technical field
The present invention relates to the synthetic method of Latamoxef Sodium intermediate, i.e. [1R-[1a, 5a]]-3-methyl-2-(7-oxo-3-phenyl-4-oxa--2,6-diazabicylo [3.2.0] hept-2-ene"-6-yl)-preparation method of 3-butenoic acid benzhydryl ester.In order to solve the committed step in the oxacephem parent nucleus building-up process, specifically be applied to 6-β-benzamide-4-oxo-penicillanic acid benzhydryl ester open loop desulfurization and obtain [1R-[1a, 5a]]-3-methyl-2-(7-oxo-3-phenyl-4-oxa--2,6-diazabicylo [3.2.0] hept-2-ene"-6-yl)-reaction process of 3-butenoic acid benzhydryl ester.
Its reaction process is as follows:
Background technology
Latamoxef Sodium is complete synthetic product, and structure is similar to cynnematin, but S is replaced by O in the parent nucleus, is oxacephem (oxacephem) class, and its mechanism of action, antimicrobial spectrum are similar a bit to other third generation cephalosporin, and is stable to β-Nei Xiananmei.
Latamoxef Sodium synthetic key is to obtain the parent nucleus that S is replaced by oxygen; in the reaction process of external at present realization preparation oxacephem parent nucleus; main reaction process all is to be raw material by 6-APA; 6-APA → 4 sulphur atoms of protection amino → protection carboxyl → oxidation obtain intermediate 6-β-benzamide-4-oxo-penicillanic acid benzhydryl ester (compound 1); obtain the important intermediate [1R-[1a of parent nucleus again through high temperature open loop desulfurization; 5a]]-3-methyl-2-(7-oxo-3-phenyl-4-oxa--2,6-diazabicylo [3.2.0] hept-2-ene"-6-yl)-3-butenoic acid benzhydryl ester (compound 2).And the selection of sweetening agent often has trimethoxy phosphine, two kinds of materials of tributylphosphine.
But find that in actual tests adopt trimethoxy phosphorus to make sweetening agent, solvent is toluene and 1.2-ethylene dichloride, residual reaching below 1.0% of 10 hours three steps carried out in reaction, and yield reaches more than 75%.The structure that nuclear-magnetism is determined is a target product, but mass spectrum result displayed molecular weight is to Duo 16 than the molecular weight of target product, judges that this step reaction is that sulphur participates in having formed a new five-ring after breaking ring, but not oxygen Cheng Huan.The former is the intermediate of synthetic cephalosporin analog antibiotic, and the latter is the intermediate of synthetic oxygen cephalosporin analog antibiotic.Therefore, trimethoxy phosphorus is done sweetening agent does not reach desulfurization in this reaction effect.
And adopt tributyl phosphorus to make sweetening agent, and solvent is toluene and 1, the mixture of 2-ethylene dichloride, reflux temperature are 100 ℃, add division box simultaneously, react 3.5 hours, and residual reaching about 2%, along with the prolongation in reaction times, by product increases.Use methanol crystallization, yield about 40%, purity reaches more than 97%, and product proves target product behind nuclear-magnetism and mass spectral characteristi.But because tributylphosphine has strong reducing property, meet high heat, naked light or contact, the incendiary of causing danger is arranged with oxygenant; Adding owing to division box simultaneously makes the uncontrollability of reaction increase, and yield is low, the production cost height.These shortcomings make this reaction be not suitable for being applied to suitability for industrialized production.
Summary of the invention
The present invention seeks to overcome the deficiency of above-mentioned sweetening agent in technological process, adopt a kind of new sweetening agent---triphenyl phosphorus, and in benzene class and alkanes mixed solvent back flow reaction, by the mixed solvent crystallization, remove by product, with the alcohols be again crystallizing system reach realize synthetic [1R-[1a, 5a]]-3-methyl-2-(7-oxo-3-phenyl-4-oxa--2,6-diazabicylo [3.2.0] hept-2-ene"-6-yl)-purpose of 3-butenoic acid benzhydryl ester.Its reaction is as follows:
For realizing the object of the invention, this its feature of Latamoxef Sodium intermediate preparation method comprises the steps:
A, add in mixing solutions that benzene class and alkanes solvent form with the ratio of weight and number of 1:0.5～0.7 6-β-benzamide-4-oxo-penicillanic acid benzhydryl ester and triphenyl phosphorus after, under 80～105 ℃ reflux temperature, react;
B, when above-mentioned reaction 6-β-benzamide-4-oxo-penicillanic acid benzhydryl ester residual≤1.0% the time, at 50～60 ℃ of following concentrating under reduced pressure, the mixed solvent that adds acetonitrile and alcohols again in enriched material cooled to growing the grain below 0 ℃ 8～10 hours after fully stirring;
C, remove by filter the impurity triphenyl sulphur phosphorus of generation, use alcohols solvent washing leaching cake again, then merging filtrate and washing lotion;
D, with above-mentioned amalgamation liquid at 40～50 ℃ of following concentrating under reduced pressure, in enriched material, add the alcohols solvent then, be warmed up to 40～50 ℃ of abundant stirring and dissolving, and then cool to 10～15 ℃ of following crystallizatioies;
E, above-mentioned crystallization of separating out are through 8～12 hours after-filtration of growing the grain, 40～60 ℃ of vacuum-dryings are after 5～6 hours, make product [1R-[1a of the present invention, 5a]]-3-methyl-2-(7-oxo-3-phenyl-4-oxa--2,6-diazabicylo [3.2.0] hept-2-ene"-6-yl)-3-butenoic acid benzhydryl ester.
Compound 1 is that the ratio of weight and number of 6-β-benzamide-4-oxo-penicillanic acid benzhydryl ester and action solvent mixing solutions is 1:8～13 among the above-mentioned steps a; The ratio of weight and number of benzene class solvent and alkanes solvent is 1:0.15～0.3.
The ratio of weight and number of acetonitrile and alcohols solvent is 1:0.8～1.3 among the above-mentioned steps b.
The present invention has the following advantages:
1, owing to selected triphenylphosphine to replace the big tributylphosphine sweetening agent of toxicity hazard, cancels uppity dewatering unit on the production unit, simplified production unit, be beneficial to suitability for industrialized production.
2, owing to adopt triphenylphosphine to make sweetening agent, the by product triphenyl phosphine sulfide of generation can crystallize out with solid form in the mixed system of acetonitrile and alcohols solvent, has reduced follow-up removal of impurities process, thereby helps guaranteeing the raising of quality product and yield.
3, through comprehensively measuring and calculating, adopt the yield of technology compound 2 of the present invention to bring up to 58% by 40% of former technology, material cost can reduce about 600 yuan/Kg, has the stronger market competitiveness, remarkable in economical benefits.
4, the invention enables the committed step of preparation oxacephems antibiotic parent nucleus to be more suitable for, for the large-scale production of oxacephem parent nucleus provides technical qualification in industrialization.Can make Latamoxef Sodium, Flomoxef Sodium realize production domesticization early, can alleviate patient's economical load, have positive social benefit with broad spectrum antibiotic activity.
Embodiment
Embodiment 1: Latamoxef Sodium intermediate of the present invention i.e. [1R-[1a, 5a]]-3-methyl-2-(7-oxo-3-phenyl-4-oxa--2,6-diazabicylo [3.2.0] hept-2-ene"-6-yl)-preparation method of 3-butenoic acid benzhydryl ester comprises following processing step:
A, in the 1L of dried and clean four-hole bottle, add 400mL toluene, 30g triphenylphosphine, 45g 6-β-benzamide-4-oxo-penicillanic acid benzhydryl ester and 90mL1.2-ethylene dichloride successively, behind the good reflux of frame, open water coolant, temperature reacts material at 98～105 ℃ in the control under reflux state;
B, when above-mentioned reaction 6-β-benzamide-4-oxo-penicillanic acid benzhydryl ester residual≤1.0% the time, reaction finishes, under 50～60 ℃, be evaporated to evaporate to dryness then, in the enriched material of evaporate to dryness, add 300mL methyl alcohol and 280mL acetonitrile mixed solvent again, after being stirred well to the dissolving clarification, cooled to growing the grain below 0 ℃ 8～10 hours, cooling growing the grain below 0 ℃ is for by product triphenyl phosphine sulfide thoroughly being separated out, avoiding influencing the purity of target product;
C, remove by filter the impurity triphenyl sulphur phosphorus of generation, add 30mL methyl alcohol solvent washing leaching cake again, then merging filtrate and washing lotion;
D, with above-mentioned amalgamation liquid outside temperature be evaporated under 40～50 ℃ thick, in enriched material, add 400mL Virahol solvent then, be warming up to 45 ℃ of abundant stirring and dissolving, and then cool to 10～15 ℃ of following crystallizatioies, wherein the spissated outer temperature of underpressure distillation≤50 ℃ is the generation of avoiding side reaction in concentration process;
E, above-mentioned crystallization insulated and stirred growing the grain of separating out 8～12 hours, again crystal solution is filtered, filter cake washing is to off-white color, 55 ℃ of vacuum-dryings are after 5～6 hours, make finished product [1R-[1a of the present invention, 5a]]-3-methyl-2-(7-oxo-3-phenyl-4-oxa--2,6-diazabicylo [3.2.0] hept-2-ene"-6-yl)-3-butenoic acid benzhydryl ester 24.3g.
Embodiment 2: the present embodiment difference from Example 1 is,
Add 380mL benzene successively in a, the dried and clean 1L four-hole bottle, the 32g triphenylphosphine, 45g 6-β-benzamide-4-oxo-penicillanic acid benzhydryl ester, the 100mL methylene dichloride, behind the good reflux of frame, open water coolant, temperature reacts material at 98～105 ℃ in the control under reflux state;
B, when above-mentioned reaction 6-β-benzamide-4-oxo-penicillanic acid benzhydryl ester residual≤1.0% the time, reaction finishes, under 50～60 ℃, be evaporated to evaporate to dryness then, in the enriched material of evaporate to dryness, add 300mL ethanol and 280mL acetonitrile mixed solvent again, after being stirred well to the dissolving clarification, cooled to the growing the grain of insulation below 0 ℃ 10 hours;
C, remove by filter the impurity triphenyl sulphur phosphorus of generation, add 30mL ethanol solvent washing leaching cake again, then merging filtrate and washing lotion;
D, with above-mentioned amalgamation liquid outside temperature be evaporated under 40～50 ℃ thickly, in enriched material, add 400mL methyl alcohol solvent then, be warming up to 50 ℃ of abundant stirring and dissolving after, cool to 10～15 ℃ of following crystallizatioies again;
E, above-mentioned crystallization insulated and stirred growing the grain of separating out 8～12 hours, again crystal solution is filtered, filter cake washing is to off-white color, 50 ℃ of vacuum-dryings are after 5～6 hours, make finished product [1R-[1a of the present invention, 5a]]-3-methyl-2-(7-oxo-3-phenyl-4-oxa--2,6-diazabicylo [3.2.0] hept-2-ene"-6-yl)-3-butenoic acid benzhydryl ester 23g.
Embodiment 3: the present embodiment difference from Example 1 is,
Add 400mL benzene successively in a, the dried and clean 1L four-hole bottle, 30g triphenylphosphine, 45g 6-β-benzamide-4-oxo-penicillanic acid benzhydryl ester, the 100mL methylene dichloride, open water coolant behind the good reflux of frame, temperature reacts material at 98～105 ℃ in the control under reflux state;
B, when above-mentioned reaction 6-β-benzamide-4-oxo-penicillanic acid benzhydryl ester residual≤1.0% the time, reaction finishes, under 50～60 ℃, be evaporated to evaporate to dryness then, in the enriched material of evaporate to dryness, add 300mL methyl alcohol and 280mL acetonitrile mixed solvent again, after being stirred well to the dissolving clarification, cooled to growing the grain below 0 ℃ 8～10 hours;
C, remove by filter the impurity triphenyl sulphur phosphorus of generation, add 30mL methanol wash filter cake again, then merging filtrate and washing lotion;
D, with above-mentioned amalgamation liquid outside temperature be evaporated under 40～50 ℃ thickly, in enriched material, add the 400mL Virahol then, be warming up to 40 ℃ of abundant stirring and dissolving after, cool to 10～15 ℃ of following crystallizatioies again;
E, above-mentioned crystallization insulated and stirred growing the grain of separating out 8～12 hours, again crystal solution is filtered, filter cake washing is to off-white color, 60 ℃ of vacuum-dryings are after 5～6 hours, make finished product [1R-[1a of the present invention, 5a]]-3-methyl-2-(7-oxo-3-phenyl-4-oxa--2,6-diazabicylo [3.2.0] hept-2-ene"-6-yl)-3-butenoic acid benzhydryl ester 21.5g.
Claims (3)
1. Latamoxef Sodium intermediates preparation, its feature comprises the steps:
A, add in mixing solutions that benzene class and alkanes solvent form with the ratio of weight and number of 1:0.5～0.7 6-β-benzamide-4-oxo-penicillanic acid benzhydryl ester and triphenyl phosphorus after, under 80～105 ℃ reflux temperature, react;
B, when above-mentioned reaction 6-β-benzamide-4-oxo-penicillanic acid benzhydryl ester residual≤1.0% the time, at 50～60 ℃ of following concentrating under reduced pressure, the mixed solvent that adds acetonitrile and alcohols again in enriched material cooled to growing the grain below 0 ℃ 8～10 hours after fully stirring;
C, remove by filter the impurity triphenyl sulphur phosphorus of generation, use alcohols solvent washing leaching cake again, then merging filtrate and washing lotion;
D, with above-mentioned amalgamation liquid at 40～50 ℃ of following concentrating under reduced pressure, in enriched material, add the alcohols solvent then, be warmed up to 40～50 ℃ of abundant stirring and dissolving, and then cool to 10～15 ℃ of following crystallizatioies;
E, above-mentioned crystallization of separating out make product of the present invention [1R-[1a, 5a] through 8～12 hours after-filtration of growing the grain]-3-methyl-2-(7-oxo-3-phenyl-4-oxa--2,6-diazabicylo [3.2.0] hept-2-ene"-6-yl)-3-butenoic acid benzhydryl ester.
2. Latamoxef Sodium intermediates preparation according to claim 1 is characterized in that the ratio of weight and number of 6-β-benzamide among the described step a-4-oxo-penicillanic acid benzhydryl ester and benzene class and alkanes solvent mixing solutions is 1:8～13; The ratio of weight and number of benzene class solvent and alkanes solvent is 1:0.15～0.3.
3. Latamoxef Sodium intermediates preparation according to claim 1 is characterized in that the ratio of weight and number of acetonitrile and alcohols solvent is 1:0.8～1.3 among the described step b.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011102812908A CN102286004A (en) | 2011-09-21 | 2011-09-21 | Method for preparing latamoxef sodium intermediate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011102812908A CN102286004A (en) | 2011-09-21 | 2011-09-21 | Method for preparing latamoxef sodium intermediate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102286004A true CN102286004A (en) | 2011-12-21 |
Family
ID=45332780
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011102812908A Pending CN102286004A (en) | 2011-09-21 | 2011-09-21 | Method for preparing latamoxef sodium intermediate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102286004A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102875571A (en) * | 2012-10-30 | 2013-01-16 | 陕西思尔生物科技有限公司 | Latamoxef Sodium midbody synthetic method |
| CN111848646A (en) * | 2020-07-29 | 2020-10-30 | 绍兴众昌化工股份有限公司 | Preparation method of methyl thiazoline |
| CN113387960A (en) * | 2021-07-14 | 2021-09-14 | 海南海灵化学制药有限公司 | Refining method of latamoxef sodium intermediate |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4183855A (en) * | 1977-02-25 | 1980-01-15 | Shionogi & Co., Ltd. | Oxazolinoazetidinylbutyric acid derivatives |
| US4271296A (en) * | 1977-01-10 | 1981-06-02 | Shionogi & Co., Ltd. | Oxazolines |
| US4366316A (en) * | 1977-02-15 | 1982-12-28 | Shionogi & Co., Ltd. | 1-Oxadethiacepham compounds and process for producing said compounds |
| US4405420A (en) * | 1981-09-28 | 1983-09-20 | Chevron Research Company | Catalyzed electrochemical gasification of carbonaceous materials at anode and electrowinning of metals at cathode |
| EP0101602A1 (en) * | 1982-08-20 | 1984-02-29 | Bayer Ag | Derivatives of 7-oxo-4-oxa-diazabicyclo-(3.2.0)-hept-2-en not substituted in position 6, processes for their preparation and their use as intermediates in the synthesis of beta-lactam antibiotics |
| JPS5944390A (en) * | 1982-09-07 | 1984-03-12 | Shionogi & Co Ltd | Preparation of oxazoline compound |
-
2011
- 2011-09-21 CN CN2011102812908A patent/CN102286004A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4271296A (en) * | 1977-01-10 | 1981-06-02 | Shionogi & Co., Ltd. | Oxazolines |
| US4366316A (en) * | 1977-02-15 | 1982-12-28 | Shionogi & Co., Ltd. | 1-Oxadethiacepham compounds and process for producing said compounds |
| US4183855A (en) * | 1977-02-25 | 1980-01-15 | Shionogi & Co., Ltd. | Oxazolinoazetidinylbutyric acid derivatives |
| US4405420A (en) * | 1981-09-28 | 1983-09-20 | Chevron Research Company | Catalyzed electrochemical gasification of carbonaceous materials at anode and electrowinning of metals at cathode |
| EP0101602A1 (en) * | 1982-08-20 | 1984-02-29 | Bayer Ag | Derivatives of 7-oxo-4-oxa-diazabicyclo-(3.2.0)-hept-2-en not substituted in position 6, processes for their preparation and their use as intermediates in the synthesis of beta-lactam antibiotics |
| JPS5944390A (en) * | 1982-09-07 | 1984-03-12 | Shionogi & Co Ltd | Preparation of oxazoline compound |
Non-Patent Citations (5)
| Title |
|---|
| NAGATA, W. ET AL: "Straightforward synthesis of 7a-methoxy-1-oxacephems from penicillins", 《PHILOS. TRANS. R. SOC. LONDON, SER. B》 * |
| SADAO YAMAMOTO ET AL.: "One-step synthesis of Oxazolinoazetidinones From Penicilin Sulfoxides: Potential Intermediates for l-oxacephem synthesis", 《TETRAHEDRON LETTERS》 * |
| YOSHIOKA, MITSURU ET AL: "Stereocontrolled, straightforward synthesis of 3-substituted methyl 7a-methoxy-1-oxacephems", 《TETRAHEDRON LETTERS》 * |
| 吴良春: "氧头孢中间体的合成及路线优化", 《中国优秀硕士学位论文全文数据库（电子期刊）工程科技I辑》 * |
| 胡志等: "(6R,7R)-7-苯甲酰胺基-3-氯甲基-7-甲氧基-8-氧代-5-氧杂-1-氮杂二环[4.2.0]辛-2-烯-羧酸二苯甲酯的合成", 《中国医药工业杂志》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102875571A (en) * | 2012-10-30 | 2013-01-16 | 陕西思尔生物科技有限公司 | Latamoxef Sodium midbody synthetic method |
| CN111848646A (en) * | 2020-07-29 | 2020-10-30 | 绍兴众昌化工股份有限公司 | Preparation method of methyl thiazoline |
| CN113387960A (en) * | 2021-07-14 | 2021-09-14 | 海南海灵化学制药有限公司 | Refining method of latamoxef sodium intermediate |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107266294B (en) | Method for purifying guaiacol primary product for catalytic synthesis of catechol and methanol | |
| CN102286004A (en) | Method for preparing latamoxef sodium intermediate | |
| CN108358777A (en) | A kind of preparation method based on three three potassium ferric oxalates of hydration containing vanadium solution | |
| CN102875571A (en) | Latamoxef Sodium midbody synthetic method | |
| CN104130262A (en) | Ertapenem and ertapenem side chain, as well as preparation methods of ertapenem and ertapenem side chains | |
| CN111777513B (en) | Preparation method of high-purity methyl oleate | |
| CN103420979A (en) | Esomeprazole sodium refining method | |
| CN103408452A (en) | Green synthesis process for p-chloro-o-nitroacetoanilide | |
| CN113277926B (en) | Method for separating high-purity isomers of tetramethyl biphenyl by rectification-melt crystallization coupling | |
| CN101134728A (en) | Process for the separation of nitro phthalandione isomer mixture | |
| CN103044280B (en) | Preparation method of tigecycline | |
| CN1740138A (en) | Process of preparing 4-nitro phthalic acid from the reaction mother liquor of nitrating phthalic anhydride to prepare 3-nitro phthalic acid | |
| CN109053585B (en) | Synthetic method of triclabendazole | |
| CN102964252A (en) | Technology for preparing propyl gallate by utilizing mixed catalyst | |
| CN113956258B (en) | Preparation method of indolo [2,3-A ] carbazole by adopting acidic ionic liquid | |
| CN110885300A (en) | Synthetic process of hydroxybenzene sulfonate compound | |
| CN109734619A (en) | A method of impurity A, C are isolated and purified from phenobarbital production waste residue | |
| CN115594578B (en) | Method for purifying erucic acid by adopting steam stripping mode | |
| CN109608398A (en) | A kind of preparation method of Edaravone | |
| CN112661727B (en) | Purification method of 7- (2, 2-trichloroethyl oxycarbonyl) taxol | |
| KR20130074284A (en) | Method for preparing naphthalene | |
| WO2023216317A1 (en) | Method for synthesizing nirmatrelvir intermediate | |
| KR102412089B1 (en) | A method for refining DMTS | |
| CN109438270B (en) | Preparation method of di (p-N, N-dialkyl aminobenzoic acid) -N-alkyl diethanol amine ester | |
| CN101134729A (en) | Process for the separation of nitro phthalandione isomer mixture |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20111221 |