CN102234289B - Novel method for preparing ceftiofur intermediate - Google Patents
Novel method for preparing ceftiofur intermediate Download PDFInfo
- Publication number
- CN102234289B CN102234289B CN201010180899.1A CN201010180899A CN102234289B CN 102234289 B CN102234289 B CN 102234289B CN 201010180899 A CN201010180899 A CN 201010180899A CN 102234289 B CN102234289 B CN 102234289B
- Authority
- CN
- China
- Prior art keywords
- acid
- ethyl acetate
- reaction
- amino
- preparation
- 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.)
- Expired - Fee Related
Links
- 229960005229 ceftiofur Drugs 0.000 title claims abstract description 18
- ZBHXIWJRIFEVQY-IHMPYVIRSA-N ceftiofur Chemical compound S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CSC(=O)C1=CC=CO1 ZBHXIWJRIFEVQY-IHMPYVIRSA-N 0.000 title claims abstract description 18
- 238000000034 method Methods 0.000 title abstract description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 54
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 26
- 238000006243 chemical reaction Methods 0.000 claims abstract description 20
- 239000002253 acid Substances 0.000 claims abstract description 15
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims abstract description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000008399 tap water Substances 0.000 claims abstract description 7
- 235000020679 tap water Nutrition 0.000 claims abstract description 7
- OFTKFKYVSBNYEC-UHFFFAOYSA-N 2-furoyl chloride Chemical compound ClC(=O)C1=CC=CO1 OFTKFKYVSBNYEC-UHFFFAOYSA-N 0.000 claims abstract description 6
- HSHGZXNAXBPPDL-HZGVNTEJSA-N 7beta-aminocephalosporanic acid Chemical compound S1CC(COC(=O)C)=C(C([O-])=O)N2C(=O)[C@@H]([NH3+])[C@@H]12 HSHGZXNAXBPPDL-HZGVNTEJSA-N 0.000 claims abstract description 6
- UNWSCLFRWCYCHG-UHFFFAOYSA-N ethyl acetate;trifluoroborane Chemical compound FB(F)F.CCOC(C)=O UNWSCLFRWCYCHG-UHFFFAOYSA-N 0.000 claims abstract description 5
- 235000019260 propionic acid Nutrition 0.000 claims abstract description 5
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims abstract description 5
- HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 claims abstract description 4
- 238000002360 preparation method Methods 0.000 claims description 19
- 125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 claims description 12
- IKWLIQXIPRUIDU-ZCFIWIBFSA-N (6r)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound OC(=O)C1=CCS[C@@H]2CC(=O)N12 IKWLIQXIPRUIDU-ZCFIWIBFSA-N 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 3
- 239000012065 filter cake Substances 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 3
- 238000010792 warming Methods 0.000 claims description 3
- 229910021529 ammonia Inorganic materials 0.000 claims description 2
- 238000001816 cooling Methods 0.000 claims description 2
- 239000012153 distilled water Substances 0.000 claims description 2
- 239000010410 layer Substances 0.000 claims description 2
- 239000012044 organic layer Substances 0.000 claims description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 abstract description 4
- 230000003472 neutralizing effect Effects 0.000 abstract 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 abstract 1
- 239000000543 intermediate Substances 0.000 description 15
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- RFLHUYUQCKHUKS-JUODUXDSSA-M Ceftiofur sodium Chemical compound [Na+].S([C@@H]1[C@@H](C(N1C=1C([O-])=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CSC(=O)C1=CC=CO1 RFLHUYUQCKHUKS-JUODUXDSSA-M 0.000 description 3
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 3
- 229960004467 ceftiofur sodium Drugs 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- KEQFDTJEEQKVLM-JUODUXDSSA-N (6r,7r)-7-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-3-(furan-2-carbonylsulfanylmethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid;hydron;chloride Chemical compound Cl.S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CSC(=O)C1=CC=CO1 KEQFDTJEEQKVLM-JUODUXDSSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 229960001356 ceftiofur hydrochloride Drugs 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 229910015900 BF3 Inorganic materials 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- 108090000279 Peptidyltransferases Proteins 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 229940059260 amidate Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 238000010586 diagram 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
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- NPUKDXXFDDZOKR-LLVKDONJSA-N etomidate Chemical compound CCOC(=O)C1=CN=CN1[C@H](C)C1=CC=CC=C1 NPUKDXXFDDZOKR-LLVKDONJSA-N 0.000 description 1
- 230000002070 germicidal effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- CXHHBNMLPJOKQD-UHFFFAOYSA-M methyl carbonate Chemical compound COC([O-])=O CXHHBNMLPJOKQD-UHFFFAOYSA-M 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 238000000643 oven drying Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000273 veterinary drug Substances 0.000 description 1
Landscapes
- Cephalosporin Compounds (AREA)
Abstract
The invention relates to a novel method for preparing a ceftiofur intermediate. The method comprises the steps of: dropwise adding furoyl chloride into an ethyl acetate solution containing sodium hydrosulphide, adding tap water after the reaction, and neutralizing and dehydrating to obtain an ethyl acetate solution containing furan-2-carbothiolic acid; adding 7-aminocephalosporanic acid and ethyl acetate into a reacting bottle, then adding propionic acid and the ethyl acetate solution containing the furan-2-carbothiolic acid, at last adding boron trifluoride ethyl acetate for reaction; performing acidolysis by using hydrochloric acid after the reaction, neutralizing by using dilute ammonia water in a water phase, and separating to obtain the ceftiofur intermediate, namely 7-amino-3-[2-(furylcarbonyl)sulfomethyl]-3-cephem-4-carboxylic acid, wherein the yield of the intermediate reaches 97%.
Description
Technical field
The present invention relates to the preparation method of drug chemical, specifically, is a kind of ceftiofur intermediates preparation.
Background technology
7-amino-3-[2-(furyl carbonyl) thiomethyl]-3-cephem-4-carboxylic acid is the key intermediate of producing ceftiofur sodium, ceftiofur sodium (ceftiofur sodium) is that PharmaciaUpjohn company is in the cephalosporins veterinary drug of the exploitation eighties in 20th century.Its mechanism of action is to act on the bacterium transpeptidase and block the synthetic of cell walls, presents germicidal action, is used for the treatment of and controls the bacillary enteron aisle of livestock and respiratory tract infection.It is synthetic mainly to be raw material with the 7-amino-cephalosporanic acid, 3 condensation reaction and 7 amidate action takes place make ceftiofur acid, makes ceftiofur hydrochloride with the concentrated hydrochloric acid reaction then, changes into sodium salt finally by ceftiofur hydrochloride.
US Patent No. 6476220 and US6800756 etc. have set forth 7-amino-3-[2-(furyl carbonyl) thiomethyl]-preparation method of 3-cephem-4-carboxylic acid.Basic way is that sodium sulphite is dissolved in the tap water, drips furoyl chloride, and it is extremely acid with hydrochloric acid or phosphoric acid adjust pH that reaction finishes the back, obtains containing the solution of furans-2-carbothiolic acid then with ethyl acetate extraction.7-amino-cephalosporanic acid is dissolved in the ethyl acetate, adds above-mentioned solution, feeds boron triflouride gas and reacts, and obtains intermediate at aqueous phase with hydrochloric acid or phosphoric acid neutralization then.
Chinese patent CN02826649.8 has also set forth 7-amino-3-[2-(furyl carbonyl) thiomethyl]-preparation method of 3-cephem-4-carboxylic acid, basic way is equal to US Patent No. 6476220 and US6800756 etc.Chinese patent CN01142350.1 has set forth the method for producing the ceftiofur intermediate with the complex compound of methylcarbonate and its boron trifluoride.
The yield of above-mentioned several method is all below 80%.
Summary of the invention
The purpose of this invention is to provide the new preparation method of a kind of ceftiofur intermediate.This preparation method's yield height, the intermediate preparation cost is low, and the purity height has the good commercial prospect.
In order to achieve the above object, the present invention is by the following technical solutions:
Furoyl chloride and Sodium sulfhydrate react in organic solvent, obtain furans-2-carbothiolic acid solution, in solvent, under catalyst action, react with 7-amino-cephalosporanic acid then, obtain ceftiofur intermediate 7-amino-3-[2-(furyl carbonyl) thiomethyl through acid-alkali treatment]-3-cephem-4-carboxylic acid.
Described organic solvent is ethyl acetate.
Described solvent is ethyl acetate and propionic acid.
Described catalyzer is boron trifluoride ethyl acetate complex compound.
Described soda acid is hydrochloric acid and ammoniacal liquor.
Described hydrochloric acid is 11% hydrochloric acid, and described alkali is 10% ammoniacal liquor.
The synthetic route of preparation ceftiofur intermediate of the present invention, as described below:
Ceftiofur intermediates preparation of the present invention more specifically, comprises following steps:
(1), the preparation of furans-2-carbothiolic acid
In the reaction vessel that agitator, thermometer and constant pressure funnel are housed, add Sodium sulfhydrate, ethyl acetate, drip furoyl chloride, dropwise room temperature reaction 1-2 hour.Add tap water, use in the hydrochloric acid and pH to 1-2, divide to fall water layer, organic layer adds no dried over sodium sulfate, filters, and obtains containing the ethyl acetate solution of furans-2-carbothiolic acid.
(2), 7-amino-3-[2-(furyl carbonyl) thiomethyl]-preparation of 3-cephem-4-carboxylic acid
In the reaction vessel that agitator, thermometer are housed, add ethyl acetate, propionic acid, 7-amino-cephalosporanic acid, add ethyl acetate solution and the boron trifluoride ethyl acetate that contains furans-2-carbothiolic acid then, be warming up to 40-50 ℃ of reaction 2 hours.After reaction finishes, the ice bath cooling adds hydrochloric acid and reacted 30 minutes, filter, filter cake is suspended in the distilled water, transfer pH at 3.3-3.5 with weak ammonia, filtering separation, 35-40 ℃ of drying obtains off-white color ceftiofur intermediate 7-amino-3-[2-(furyl carbonyl) thiomethyl]-3-cephem-4-carboxylic acid.
Ceftiofur intermediate 7-amino-3-[2-(furyl carbonyl) thiomethyl that the present invention's reaction obtains]-3-cephem-4-carboxylic acid, instrument detects by analysis, and is consistent with the standard diagram of this material that document is put down in writing.Whole inventive method prepares ceftiofur intermediate 7-amino-3-[2-(furyl carbonyl) thiomethyl]-to be stabilized in 97%, HPLC purity be 95% to the total recovery of 3-cephem-4-carboxylic acid.
The present invention has characteristics such as yield height, quality is good, cost is low, is particularly suitable for suitability for industrialized production.
Embodiment
Be embodiments of the invention below, described embodiment just is used for illustrating the present invention, and should not be considered to be limitation of the present invention.
Embodiment 1
The preparation of furans-2-carbothiolic acid
In the 20ml ethyl acetate, add 8.0gNaSH.Splash into the 13.6g furoyl chloride under the room temperature, dropwise the back and stir 1h.Reaction finishes, and adds the 30ml tap water, stirs after 10 minutes, is neutralized between the pH=0.5-1.0 with concentrated hydrochloric acid.Tell organic phase, add the anhydrous sodium sulfate drying after-filtration.Be directly used in next step reaction.
Embodiment 2
7-amino-3-[2-(furyl carbonyl) thiomethyl]-preparation of 3-cephem-4-carboxylic acid
Under the room temperature condition, in clean dry reaction flask, drop into ethyl acetate 20ml, the 1ml propionic acid is opened and is stirred, and drops into 7-ACA15g then, drops into the ethyl acetate solution of the furans-2-carbothiolic acid of above-mentioned preparation.Be warming up to 43-45 ℃, add 21ml boron trifluoride ethyl acetate.Keep 43-45 ℃ of reaction 2 hours.Be down to room temperature, add 0.1gEDTA-2Na and 0.1g Sodium Pyrosulfite.Beginning slowly drips 11% hydrochloric acid 15ml in the feed liquid in the ice bath, reacts filtration 1.0 hours.Above-mentioned filter cake is suspended in the 50ml tap water.It is 3.3-3.5 that ammoniacal liquor with 10% is adjusted the pH value.Stirring at room 1 hour.Filtering separation, tap water washing 3 times, use washing with acetone at last 3 times, obtain Powdered loose off-white color product, 35-40 ℃ of oven drying, obtain ceftiofur intermediate 7-amino-3-[2-(furyl carbonyl) thiomethyl]-3-cephem-4-carboxylic acid 18.3g, yield 97%, HPLC purity is 95%.
More than ceftiofur intermediates preparation provided by the present invention is described in detail, used specific case herein principle of the present invention and embodiment are set forth, the explanation of above embodiment just is used for helping to understand method of the present invention and core concept thereof; Simultaneously, for one of ordinary skill in the art, according to thought of the present invention, the part that all can change in specific embodiments and applications, in sum, this description should not be construed as limitation of the present invention.
Claims (1)
1. the preparation method that the ceftiofur intermediate is new is characterized in that, comprises following steps:
(1), the preparation of furans-2-carbothiolic acid
In the reaction vessel that agitator, thermometer and constant pressure funnel are housed, add Sodium sulfhydrate, ethyl acetate, drip furoyl chloride, dropwise room temperature reaction 1-2 hour, add tap water, with in the hydrochloric acid and pH to 1-2, divide to fall water layer, organic layer adds anhydrous sodium sulfate drying, filter, obtain containing the ethyl acetate solution of furans-2-carbothiolic acid;
(2), thiomethyl 7-amino-3-[2-(furyl carbonyl)]-preparation of 3-cephem-4-carboxylic acid
In the reaction vessel that agitator, thermometer are housed, add ethyl acetate, propionic acid, 7-amino-cephalosporanic acid, add ethyl acetate solution and the boron trifluoride ethyl acetate that contains furans-2-carbothiolic acid then, be warming up to 40-50 ℃ of reaction 2 hours, after reaction finishes, the ice bath cooling adds hydrochloric acid and reacted 30 minutes, filter, filter cake is suspended in the distilled water, transfer pH at 3.3-3.5 with weak ammonia, filtering separation, 35-40 ℃ of drying obtains off-white color ceftiofur intermediate 7-amino-3-[2-(furyl carbonyl) thiomethyl]-3-cephem-4-carboxylic acid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010180899.1A CN102234289B (en) | 2010-05-02 | 2010-05-02 | Novel method for preparing ceftiofur intermediate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010180899.1A CN102234289B (en) | 2010-05-02 | 2010-05-02 | Novel method for preparing ceftiofur intermediate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102234289A CN102234289A (en) | 2011-11-09 |
| CN102234289B true CN102234289B (en) | 2013-07-10 |
Family
ID=44885460
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201010180899.1A Expired - Fee Related CN102234289B (en) | 2010-05-02 | 2010-05-02 | Novel method for preparing ceftiofur intermediate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102234289B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103804394A (en) * | 2014-01-24 | 2014-05-21 | 瑞普（天津）生物药业有限公司 | Preparation method of ceftiofur intermediate |
| CN104530085A (en) * | 2014-12-07 | 2015-04-22 | 河南领先科技药业有限公司 | New preparation method of ceftiofur sodium |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4937330A (en) * | 1985-08-12 | 1990-06-26 | The Upjohn Company | Conversion of cephalosporin hydrohalide salt to alkali metal salt |
| US20020065412A1 (en) * | 2000-11-27 | 2002-05-30 | Uthira Kumar | Cephalosporin compound and a process for its preparation |
| CN1424316A (en) * | 2001-12-11 | 2003-06-18 | 浙江海正药业股份有限公司 | Preparation of cephalosporin compound |
| WO2003059914A1 (en) * | 2002-01-15 | 2003-07-24 | Orchid Chemicals & Pharmaceuticals Limited | An improved synthesis of ceftiofur intermediate |
| WO2003093278A2 (en) * | 2002-05-03 | 2003-11-13 | Orchid Chemicals And Pharmaceuticals Limited | Process for the preparation of ceftiofur acid |
| CN1639169A (en) * | 2002-01-04 | 2005-07-13 | 奥齐德化学和制药有限公司 | An improved synthesis of ceftiofur intermediate |
-
2010
- 2010-05-02 CN CN201010180899.1A patent/CN102234289B/en not_active Expired - Fee Related
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4937330A (en) * | 1985-08-12 | 1990-06-26 | The Upjohn Company | Conversion of cephalosporin hydrohalide salt to alkali metal salt |
| US20020065412A1 (en) * | 2000-11-27 | 2002-05-30 | Uthira Kumar | Cephalosporin compound and a process for its preparation |
| CN1424316A (en) * | 2001-12-11 | 2003-06-18 | 浙江海正药业股份有限公司 | Preparation of cephalosporin compound |
| CN1639169A (en) * | 2002-01-04 | 2005-07-13 | 奥齐德化学和制药有限公司 | An improved synthesis of ceftiofur intermediate |
| WO2003059914A1 (en) * | 2002-01-15 | 2003-07-24 | Orchid Chemicals & Pharmaceuticals Limited | An improved synthesis of ceftiofur intermediate |
| WO2003093278A2 (en) * | 2002-05-03 | 2003-11-13 | Orchid Chemicals And Pharmaceuticals Limited | Process for the preparation of ceftiofur acid |
| US20030216567A1 (en) * | 2002-05-03 | 2003-11-20 | Orchid Chemicals And Pharmaceuticals Limited | New method for the preparation of ceftiofur sodium and its intermediates |
Non-Patent Citations (11)
| Title |
|---|
| 吴汝林等.头孢噻呋钠的合成工艺研究.《中国兽药杂志》.2007,第41卷(第2期),19-20. |
| 头孢噻呋的合成;朱阳等;《中国医药工业杂志》;20010620;第32卷(第6期);241-242 * |
| 头孢噻呋钠的制备;曾裕建等;《中国抗生素杂志》;20031230;第28卷(第11期);645-646 * |
| 头孢噻呋钠的合成工艺研究;吴汝林等;《中国兽药杂志》;20070220;第41卷(第2期);19-20 * |
| 实施例. |
| 曾裕建等.头孢噻呋钠的制备.《中国抗生素杂志》.2003,第28卷(第11期),645-646. |
| 朱阳等.头孢噻呋的合成.《中国医药工业杂志》.2001,第32卷(第6期),241-242. |
| 权利要求1-11 |
| 说明书第2页第5段 |
| 说明书第3页第5段 |
| 说明书第4页第2-3段. |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102234289A (en) | 2011-11-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102127092B (en) | Preparation of Everolimus | |
| US11420948B2 (en) | Synthesis method for cariprazine | |
| CN104356146B (en) | A kind of preparation method of cefotiam chloride | |
| CN104130258A (en) | Conversion method for dimers | |
| CN101921284A (en) | Preparation method of cefathiamidine | |
| CN104193765B (en) | A kind of synthetic method of cefixime | |
| CN102234289B (en) | Novel method for preparing ceftiofur intermediate | |
| CN101475539B (en) | Refining method for preparing high-purity oteracil potassium | |
| CN106279207A (en) | A kind of synthetic method of cefdinir | |
| CN103910659A (en) | Refining method for 2-nitro-4-methylsulfonyl benzoic acid, and intermediate thereof | |
| CN106636241B (en) | Method for preparing esmollin intermediate by enzyme method | |
| CN113372286B (en) | Method for preparing 1-phenyl-5-mercapto tetrazole by one-step method | |
| CN102476991B (en) | Preparation method of o-tolyacetic acid | |
| CN105777581A (en) | Cis-1-cyano-4-methoxycyclohexyl-2-(2, 5-dimethylphenyl)acetamide, preparation method and application thereof | |
| CN103087090A (en) | Synthetic method of 2-dipalmitoyl-sn-glycero-3-phosphoethanolamine | |
| CN111574384A (en) | Preparation method of chiral 1-amino-2-propanol | |
| CN104230955A (en) | Preparation method of p-hydroxy penicillin V acid and salt thereof | |
| CN104450851B (en) | A kind of preparation method for removing acetyl cefathiamidine | |
| CN114957202B (en) | Preparation method of DL-homocysteine thiolactone hydrochloride | |
| CN103450182B (en) | Preparation and purification methods of Retapamulin | |
| CN102584855B (en) | Improved method for preparing ceftiofur | |
| CN103936703A (en) | Preparation method of 5-oxaspiro[2,4]heptane-6-one and intermediate thereof | |
| CN103408418A (en) | Preparation and purification method of solid malonic acid | |
| CN115872882B (en) | Synthesis method of 3-chloro-alanine | |
| RU2778789C1 (en) | Method for obtaining s-nicotine |
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 | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20130710 Termination date: 20140502 |