CN102020664B - Synthesis method for cefdinir - Google Patents
Synthesis method for cefdinir Download PDFInfo
- Publication number
- CN102020664B CN102020664B CN 201010567721 CN201010567721A CN102020664B CN 102020664 B CN102020664 B CN 102020664B CN 201010567721 CN201010567721 CN 201010567721 CN 201010567721 A CN201010567721 A CN 201010567721A CN 102020664 B CN102020664 B CN 102020664B
- Authority
- CN
- China
- Prior art keywords
- cefdinir
- hydrochloride
- parts
- formula
- amino
- 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
- RTXOFQZKPXMALH-GHXIOONMSA-N cefdinir Chemical compound S1C(N)=NC(C(=N\O)\C(=O)N[C@@H]2C(N3C(=C(C=C)CS[C@@H]32)C(O)=O)=O)=C1 RTXOFQZKPXMALH-GHXIOONMSA-N 0.000 title claims abstract description 26
- 229960003719 cefdinir Drugs 0.000 title claims abstract description 26
- 238000001308 synthesis method Methods 0.000 title description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 36
- 239000007787 solid Substances 0.000 claims abstract description 36
- 238000006243 chemical reaction Methods 0.000 claims abstract description 29
- 239000003054 catalyst Substances 0.000 claims abstract description 21
- 239000002608 ionic liquid Substances 0.000 claims abstract description 17
- GQLGFBRMCCVQLU-XCGJVMPOSA-N (6r)-7-amino-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound S1CC(C=C)=C(C(O)=O)N2C(=O)C(N)[C@H]21 GQLGFBRMCCVQLU-XCGJVMPOSA-N 0.000 claims abstract description 15
- 230000007062 hydrolysis Effects 0.000 claims abstract description 6
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 6
- 238000010189 synthetic method Methods 0.000 claims abstract 7
- 230000020477 pH reduction Effects 0.000 claims abstract 3
- UQJVYMLSQWHWDW-WZUFQYTHSA-N [(z)-[1-(2-amino-1,3-thiazol-4-yl)-2-chloro-2-oxoethylidene]amino] acetate Chemical compound CC(=O)O\N=C(/C(Cl)=O)C1=CSC(N)=N1 UQJVYMLSQWHWDW-WZUFQYTHSA-N 0.000 claims abstract 2
- 239000011830 basic ionic liquid Substances 0.000 claims abstract 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 27
- 238000003756 stirring Methods 0.000 claims description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- 238000001816 cooling Methods 0.000 claims description 12
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 10
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims description 10
- 239000012346 acetyl chloride Substances 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- 238000001035 drying Methods 0.000 claims description 9
- 239000005457 ice water Substances 0.000 claims description 9
- 239000000284 extract Substances 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 4
- 238000001125 extrusion Methods 0.000 claims description 3
- 238000000227 grinding Methods 0.000 claims description 3
- 229910018072 Al 2 O 3 Inorganic materials 0.000 claims 2
- QDHHCQZDFGDHMP-UHFFFAOYSA-N Chloramine Chemical compound ClN QDHHCQZDFGDHMP-UHFFFAOYSA-N 0.000 claims 2
- 229910019440 Mg(OH) Inorganic materials 0.000 claims 2
- 229920002401 polyacrylamide Polymers 0.000 claims 2
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 1
- 238000002156 mixing Methods 0.000 claims 1
- 239000002244 precipitate Substances 0.000 claims 1
- 239000002585 base Substances 0.000 abstract description 18
- 239000003513 alkali Substances 0.000 abstract description 11
- 238000005516 engineering process Methods 0.000 abstract description 8
- 230000000694 effects Effects 0.000 abstract description 5
- 230000007613 environmental effect Effects 0.000 abstract description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- 239000007788 liquid Substances 0.000 description 13
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 238000000605 extraction Methods 0.000 description 8
- 239000001117 sulphuric acid Substances 0.000 description 8
- 235000011149 sulphuric acid Nutrition 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 4
- 238000006555 catalytic reaction Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- NQNPSCQAIIUOMU-UHFFFAOYSA-N CCCCCCCCC1=NC(C)=CN1.O Chemical class CCCCCCCCC1=NC(C)=CN1.O NQNPSCQAIIUOMU-UHFFFAOYSA-N 0.000 description 2
- 229930186147 Cephalosporin Natural products 0.000 description 2
- 206010013786 Dry skin Diseases 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229940124587 cephalosporin Drugs 0.000 description 2
- 150000001780 cephalosporins Chemical class 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000002815 homogeneous catalyst Substances 0.000 description 2
- -1 methylheptyl imidazoleacetic acid salt ion Chemical class 0.000 description 2
- 239000012429 reaction media Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000011973 solid acid Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- WDOUZCOFSQCLMH-UHFFFAOYSA-N 2-hexyl-5-methyl-1h-imidazole Chemical class CCCCCCC1=NC=C(C)N1 WDOUZCOFSQCLMH-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- DUEFNIPSRCNIEI-UHFFFAOYSA-N CCCCC1=NC(C)=CN1.O Chemical class CCCCC1=NC(C)=CN1.O DUEFNIPSRCNIEI-UHFFFAOYSA-N 0.000 description 1
- ZHRKCHIEPCOIIM-UHFFFAOYSA-N CCCCCCCC1=NC(C)=CN1.O Chemical class CCCCCCCC1=NC(C)=CN1.O ZHRKCHIEPCOIIM-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- ODFJOVXVLFUVNQ-UHFFFAOYSA-N acetarsol Chemical compound CC(=O)NC1=CC([As](O)(O)=O)=CC=C1O ODFJOVXVLFUVNQ-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001449 anionic compounds Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000005518 electrochemistry Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000002638 heterogeneous catalyst Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 150000002891 organic anions Chemical class 0.000 description 1
- 150000002892 organic cations Chemical class 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Landscapes
- Cephalosporin Compounds (AREA)
Abstract
本发明公开了一种头孢地尼的合成方法，包括如下步骤：式(I)所示的7-氨基-3-乙烯基-3-头孢烯-4-羧酸和式(II)所示的2-(2-氨基噻唑-4-基)-2-(Z)-(乙酰氧基亚胺基)乙酰氯，在式(III)所示的碱性离子液体中在固体碱催化剂的作用下于10～60℃下进行反应，反应结束经水解、酸化得到式(IV)所示的头孢地尼盐酸盐。本发明技术易操作，三废少，后处理方便，离子液体和固体碱可重复使用，是经济实用的绿色环保技术。 The invention discloses a synthetic method of cefdinir, comprising the steps of: 7-amino-3-vinyl-3-cephem-4-carboxylic acid shown in formula (I) and 2-(2-aminothiazol-4-yl)-2-(Z)-(acetoxyimino) acetyl chloride, in the basic ionic liquid shown in formula (III) under the effect of solid base catalyst The reaction is carried out at 10-60° C., and the cefdinir hydrochloride represented by formula (IV) is obtained through hydrolysis and acidification at the end of the reaction. The technology of the invention is easy to operate, has less three wastes, convenient post-treatment, reusable ionic liquid and solid alkali, and is an economical and practical green environmental protection technology.
Description
(1) technical field
The present invention relates to a kind of compound method of cefdinir.
(2) background technology
Cefdinir (Cefdinir) is a kind of third generation cephalosporin analog antibiotic that Japanese Teng Ze pharmaceutical industries Co., Ltd. produces, its chemistry 7 (β) by name-[2-(thiazolamine-4-yl)-2-(Z)-(hydroxyl imide base) kharophen]-3-vinyl-3-cephalo is rare-and the 4-carboxylic acid.Have broad spectrum antibiotic activity and the effect of gram positive organism is obviously strengthened, especially obvious to staphylococcus and suis effect, stable to various β-Nei phthalein amine enzyme.USP was collected in advance and has been carried in 1998.Because its good anti-microbial effect and potential medical value are both at home and abroad to its Study of synthesis method more [1～7].Though some method has higher yield, agents useful for same is comparatively expensive, and reactions step is many, severe reaction conditions, and cost is higher, perhaps the product separation difficulty.
In recent years; We just are being devoted to ion liquid synthetic and application; And the preparation of solid acid alkali catalytic agent and applied research, ionic liquid and solid acid-base are used for the synthesis technique of cephalosporins medicine as reaction medium and catalyzer, be economical and practical eco-friendly cleaner production new technology.
Ionic liquid (ionicil quids) is by organic cation and inorganic or organic anion two portions are formed, the ionic system that under room temperature and adjacent temperature, is in a liquid state.Ionic liquid has the incomparable advantage of many other materials, like the liquid temperature wide ranges, does not have significant vp; Heat stability is good; Its acid-basicity can carry out modulation as required, and many mineral compound and organic cpds etc. are had good solubility, and electrochemical window is wide etc.Based on these characteristics, ionic liquid has a wide range of applications at aspects such as extracting and separating, catalyzed reaction, electrochemistry, is expected to become 21 century the most promising green solvent and one of catalyzer.As the friendly type catalyzer of a kind of novel environmental; Ionic liquid can overcome the separation of homogeneous catalyst and reclaim difficulty, to shortcomings such as environment pollute; Having homogeneous catalyst high reaction activity and heterogeneous catalyst simultaneously concurrently is prone to and the isolating advantage of product; In organic synthesis industry, have broad application prospects, its development research gets more and more people's extensive concerning just day by day.
The solid acid alkali catalytic reaction technology replaces the use of liquid phase acid base catalysator in traditional technology, and low to the conversion unit requirement, environmental pollution is little; Product is easy to separate; Recyclable repeated use is the catalysis technique of energy-saving and emission-reduction, and boundless application prospect is arranged.
(3) summary of the invention
The technical problem that the present invention will solve provides a kind of novel synthesis of cefdinir, utilize alkali ionic liquid as reaction medium and solid alkali as catalyzer, through the CONTROL PROCESS condition, obtain a kind of green synthesis method of antibiotics.
For solving the problems of the technologies described above, the present invention adopts following technical scheme:
A kind of compound method of cefdinir; Comprise the steps: the 2-shown in the 7-amino shown in the formula (I)-3-vinyl-3-cephem-4-carboxylic acid and the formula (II) (thiazolamine-4-yl)-2-(Z)-(acetoxyl group imido grpup) Acetyl Chloride 98Min.; Under 10～60 ℃, react under the effect at solid base catalyst in the alkali ionic liquid shown in the formula (III), reaction finishes to obtain the cefdinir hydrochloride shown in the formula (IV) through hydrolysis, acidifying; Described solid base catalyst is processed by the following component of quality proportioning: γ-Al
2O
3100 parts, Mg (OH)
25～10 parts, Ca (OH)
20.1～0.5 part, 1～5 part of SEPIGEL 305,5～15 parts in water; Said solid base catalyst prepares through following method: with each component mixed grinding after 0.5～5 hour; Extrusion molding; In down oven dry 0.5～10 hour of ir lamp, then in 50～200 ℃ of dryings 1～10 hour, at last in 300～600 ℃ of roastings 1～6 hour; Cooling, drying get said solid base catalyst;
In the formula (III), R is the alkyl of C1～C10, and L is OH
-, CH
3COO
-, HCO
3 -, BF
4 -, PF
6 -
Further, the amount of substance ratio that feeds intake of said 7-amino-3-vinyl-3-cephem-4-carboxylic acid and 2-(thiazolamine-4-yl)-2-(Z)-(acetoxyl group imido grpup) Acetyl Chloride 98Min. is 1: 1～1.5.
Further, the mass ratio that feeds intake of said 7-amino-3-vinyl-3-cephem-4-carboxylic acid and said alkali ionic liquid is 1: 5～10.
Further, the mass ratio that feeds intake of said solid base catalyst and 7-amino-3-vinyl-3-cephem-4-carboxylic acid is 30～50%: 1.
Further, described solid base catalyst is preferably processed by the following component of quality proportioning: γ-Al
2O
3100 parts, Mg (OH)
210 parts, Ca (OH)
20.5 part, 3 parts of SEPIGEL 305s, 10 parts in water.
Further, the present invention is reflected under 10～60 ℃ the temperature condition and carries out, and the reaction times is generally at 0.5～5 hour.
Further, hydrolysis of the present invention, acidifying are specifically carried out according to following steps: reaction finishes, and reaction solution is used extracted in toluene, and ionic liquid in the reaction system and solid alkali can directly be used for continuing reaction.Add sulphuric acid soln in the extraction liquid and be hydrolyzed, add alkali lye (such as saturated sodium bicarbonate solution) then and transfer pH to 5.5～7.5, agitation and filtration; Tell water; Hydrochloric acid with 10% under the ice-water bath cooling is transferred pH to 1～5 (preferred 2～3), separates out faint yellow solid, filters; Washing, drying obtains the cefdinir hydrochloride shown in the formula (IV).
The present invention compared with prior art, its beneficial effect is embodied in: this technology is easy to operate, and the three wastes are few, convenient post-treatment, ionic liquid and solid alkali are reusable, are economical and practical green environmental protection techniques.
(4) embodiment
Below in conjunction with specific embodiment the present invention is described further, but protection scope of the present invention is not limited in this.
The preparation of solid alkali:
Component by the quality proportioning is following is processed: γ-Al
2O
3100 parts, Mg (OH)
210 parts, Ca (OH)
20.5 part, 3 parts of SEPIGEL 305s, 10 parts in water.
The preparation method: with each component mixed grinding after 1 hour, extrusion molding, in ir lamp oven dry 5 hours down, then in 110 ℃ of dryings 5 hours, at last in 500 ℃ of roastings 3 hours, cooling, drying, said solid base catalyst.
Embodiment 1
In 100 milliliters of there-necked flasks, add 7-amino-3-vinyl-3-cephem-4-carboxylic acid 0.23g (1mmol), 2-(thiazolamine-4-yl)-2-(Z)-(acetoxyl group imido grpup) Acetyl Chloride 98Min. 0.25g (1mmol), hydroxide methylbutyl imidazoles subsalt ionic liquid 2.3g; Solid base catalyst 0.07g adds in the reactor drum, reacts 5 hours down at 50 ℃, and reaction finishes, and reaction solution extracts with toluene 5 * 3mL; Add 30% sulphuric acid soln with volume in the extraction liquid, stirring at room 2 hours adds saturated sodium bicarbonate solution again, transfers pH=6.5; Stirring at room 30 minutes is filtered and is told insolubles, and separatory is told water; Hydrochloric acid with 10% under the ice-water bath cooling is transferred pH=2.5, separates out faint yellow solid, filters; With the ether washing, dry cefdinir hydrochloride product 0.37g, the yield 85% of getting.Purity 99.5%.MS：m/e＝395(M
+)。
Embodiment 2
In 100 milliliters of there-necked flasks, add 7-amino-3-vinyl-3-cephem-4-carboxylic acid 0.23g (1mmol), 2-(thiazolamine-4-yl)-2-(Z)-(acetoxyl group imido grpup) Acetyl Chloride 98Min. 0.37g (1.5mmol), hydroxide methylheptyl imidazoles subsalt ionic liquid 1.1g; Solid base catalyst 0.12g adds in the reactor drum, reacts 0.5 hour down at 60 ℃, and reaction finishes, and reaction solution extracts with toluene 5 * 3mL; Add 30% sulphuric acid soln with volume in the extraction liquid, stirring at room 2 hours adds saturated sodium bicarbonate solution again, transfers pH=6.5; Stirring at room 30 minutes is filtered and is told insolubles, and separatory is told water, and the hydrochloric acid with 10% under the ice-water bath cooling is transferred pH=2.5; Separate out faint yellow solid, filter, wash with ether; Dry cefdinir hydrochloride product 0.37g, yield 85%, the purity 99.6% of getting.
Embodiment 3
In 100 milliliters of there-necked flasks, add 7-amino-3-vinyl-3-cephem-4-carboxylic acid 0.23g (1mmol), 2-(thiazolamine-4-yl)-2-(Z)-(acetoxyl group imido grpup) Acetyl Chloride 98Min. 0.37g (1.5mmol), methylheptyl imidazoleacetic acid salt ion liquid 1.1g; Solid base catalyst 0.12g adds in the reactor drum, reacts 5 hours down at 10 ℃, and reaction finishes, and reaction solution extracts with toluene 5 * 3mL; Add 30% sulphuric acid soln with volume in the extraction liquid, stirring at room 2 hours adds saturated sodium bicarbonate solution again, transfers pH=6.5; Stirring at room 30 minutes is filtered and is told insolubles, and separatory is told water, and the hydrochloric acid with 10% under the ice-water bath cooling is transferred pH=2.5; Separate out faint yellow solid, filter, wash with ether; Dry cefdinir hydrochloride product 0.36g, yield 83%, the purity 99.5% of getting.
Embodiment 4
In 100 milliliters of there-necked flasks, add 7-amino-3-vinyl-3-cephem-4-carboxylic acid 0.23g (1mmol), 2-(thiazolamine-4-yl)-2-(Z)-(acetoxyl group imido grpup) Acetyl Chloride 98Min. 0.37g (1.5mmol), methyl hexyl imidazoles bicarbonate ion liquid 2g; Solid base catalyst 0.12g adds in the reactor drum, reacts 2 hours down at 30 ℃, and reaction finishes, and reaction solution extracts with toluene 5 * 3mL; Add 30% sulphuric acid soln with volume in the extraction liquid, stirring at room 2 hours adds saturated sodium bicarbonate solution again, transfers pH=6.5; Stirring at room 30 minutes is filtered and is told insolubles, and separatory is told water, and the hydrochloric acid with 10% under the ice-water bath cooling is transferred pH=2.5; Separate out faint yellow solid, filter, wash with ether; Dry cefdinir hydrochloride product 0.34g, yield 80%, the purity 99.4% of getting.
Embodiment 5
In 100 milliliters of there-necked flasks, add 7-amino-3-vinyl-3-cephem-4-carboxylic acid 0.23g (1mmol), 2-(thiazolamine-4-yl)-2-(Z)-(acetoxyl group imido grpup) Acetyl Chloride 98Min. 0.27g (1.1mmol), methylbutyl imidazoles hexafluorophosphate ionic liquid 2g; Solid base catalyst 0.12g adds in the reactor drum, reacts 2 hours down at 30 ℃, and reaction finishes, and reaction solution extracts with toluene 5 * 3mL; Add 30% sulphuric acid soln with volume in the extraction liquid, stirring at room 2 hours adds saturated sodium bicarbonate solution again, transfers pH=6.5; Stirring at room 30 minutes is filtered and is told insolubles, and separatory is told water, and the hydrochloric acid with 10% under the ice-water bath cooling is transferred pH=2.5; Separate out faint yellow solid, filter, wash with ether; Dry cefdinir hydrochloride product 0.34g, yield 80%, the purity 99.5% of getting.
Embodiment 6
In 100 milliliters of there-necked flasks, add 7-amino-3-vinyl-3-cephem-4-carboxylic acid 0.23g (1mmol), 2-(thiazolamine-4-yl)-2-(Z)-(acetoxyl group imido grpup) Acetyl Chloride 98Min. 0.25g (1mmol), hydroxide Methyl Octyl imidazoles subsalt ionic liquid 2.3g; Solid base catalyst 0.07g adds in the reactor drum, reacts 5 hours down at 50 ℃, and reaction finishes, and reaction solution extracts with toluene 5 * 3mL; Add 30% sulphuric acid soln with volume in the extraction liquid, stirring at room 2 hours adds saturated sodium bicarbonate solution again, transfers pH=5.5; Stirring at room 30 minutes is filtered and is told insolubles, and separatory is told water, and the hydrochloric acid with 10% under the ice-water bath cooling is transferred pH=2; Separate out faint yellow solid, filter, wash with ether; Dry cefdinir hydrochloride product 0.36g, yield 84%, the purity 99.6% of getting.
Embodiment 7
In 100 milliliters of there-necked flasks, add 7-amino-3-vinyl-3-cephem-4-carboxylic acid 0.23g (1mmol), 2-(thiazolamine-4-yl)-2-(Z)-(acetoxyl group imido grpup) Acetyl Chloride 98Min. 0.25g (1mmol), hydroxide Methyl Octyl imidazoles subsalt ionic liquid 2.3g; Solid base catalyst 0.07g adds in the reactor drum, reacts 5 hours down at 50 ℃, and reaction finishes, and reaction solution extracts with toluene 5 * 3mL; Add 30% sulphuric acid soln with volume in the extraction liquid, stirring at room 2 hours adds saturated sodium bicarbonate solution again, transfers pH=7; Stirring at room 30 minutes is filtered and is told insolubles, and separatory is told water, and the hydrochloric acid with 10% under the ice-water bath cooling is transferred pH=5; Separate out faint yellow solid, filter, wash with ether; Dry cefdinir hydrochloride product 0.35g, yield 83%, the purity 99.5% of getting.
Claims (6)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010567721 CN102020664B (en) | 2010-11-30 | 2010-11-30 | Synthesis method for cefdinir |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010567721 CN102020664B (en) | 2010-11-30 | 2010-11-30 | Synthesis method for cefdinir |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102020664A CN102020664A (en) | 2011-04-20 |
| CN102020664B true CN102020664B (en) | 2012-12-12 |
Family
ID=43862479
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201010567721 Expired - Fee Related CN102020664B (en) | 2010-11-30 | 2010-11-30 | Synthesis method for cefdinir |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102020664B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103665001A (en) * | 2013-12-18 | 2014-03-26 | 成都医路康医学技术服务有限公司 | Method for preparing antibacterial cefdinir |
| CN105481782B (en) * | 2015-12-25 | 2018-05-08 | 浙江工业大学 | A kind of preparation method of sulfaquinoxaline |
| CN107286148B (en) * | 2017-06-20 | 2019-10-15 | 广州市桐晖通医药科技有限公司 | A kind of preparation method of Cefdinir and its new midbody compound |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0874853B1 (en) * | 1995-12-27 | 2002-06-05 | Hanmi Pharmaceutical Co.,Ltd. | Process for preparation of cefdinir |
| CN1628118A (en) * | 2002-04-26 | 2005-06-15 | 兰贝克赛实验室有限公司 | Process for prepn. of cefdinir |
| CN101274274A (en) * | 2008-03-31 | 2008-10-01 | 浙江工业大学 | A kind of solid base catalyst and its preparation and application |
| CN101362769A (en) * | 2007-08-06 | 2009-02-11 | 艾斯.多伯法股份公司 | Synthetic method of cefdinir |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ITMI20022076A1 (en) * | 2002-10-01 | 2004-04-02 | Antibioticos Spa | INTERMEDIATE SALTS OF CEFDINIR. |
-
2010
- 2010-11-30 CN CN 201010567721 patent/CN102020664B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0874853B1 (en) * | 1995-12-27 | 2002-06-05 | Hanmi Pharmaceutical Co.,Ltd. | Process for preparation of cefdinir |
| CN1628118A (en) * | 2002-04-26 | 2005-06-15 | 兰贝克赛实验室有限公司 | Process for prepn. of cefdinir |
| CN101362769A (en) * | 2007-08-06 | 2009-02-11 | 艾斯.多伯法股份公司 | Synthetic method of cefdinir |
| CN101274274A (en) * | 2008-03-31 | 2008-10-01 | 浙江工业大学 | A kind of solid base catalyst and its preparation and application |
Non-Patent Citations (2)
| Title |
|---|
| 林桂椿等.头孢地尼的合成.《合成化学》.2001,第9卷(第5期),383-385. * |
| 贡长生.第二章 绿色化学原理.《绿色化学》.华中科技大学出版社,2008,第32-34、38-40页. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102020664A (en) | 2011-04-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102020664B (en) | Synthesis method for cefdinir | |
| US12054404B2 (en) | Preparation method and application of clay/tannic acid/metal ion composite material for efficient adsorption of antibiotics | |
| CN111686694B (en) | MIL-101 material preparation method and application | |
| CN108311170A (en) | A kind of composite modified montmorillonite catalysis material and preparation method thereof | |
| CN102605014A (en) | L-2-reanal biological preparation method | |
| CN101570543B (en) | A kind of preparation method of mezlocillin sodium solvent crystallization | |
| CN105348154A (en) | Method for recycling sulfosalicylic acid from doxycycline production waste liquid | |
| CN103724279B (en) | One step to form the loop prepares the convenient synthetic method of 2-methyl-4-amino-5-amino methylpyrimidine | |
| CN105688985A (en) | Immobilized ionic liquid catalyst and preparation method thereof | |
| CN101768168B (en) | Method for synthesizing cephalosporin intermediate | |
| CN102010335A (en) | Method for synthesizing tributyl citrate under catalysis of functional ionic liquid | |
| CN101445436A (en) | Method for preparing medical compound chlorphenesin | |
| CN101671349B (en) | New method for preparing cefuroxime sodium compound | |
| CN102614919B (en) | Sulfonated cross-linked chitosan resin type solid acid catalyst and preparation method thereof | |
| CN103172754A (en) | Method for preparing carboxymethylcellulose from ionic liquid | |
| CN103664527B (en) | A kind of method of clean preparation 2,4-bis-chloro-α-chloromethylbenzene methyl alcohol | |
| CN101851249A (en) | Method for preparing cefcapene pivoxil hydrochloride | |
| CN101851198A (en) | Preparation method of ciprofloxacin hydrochloride | |
| CN101607965A (en) | A kind of novel process for preparing Wy-44635 | |
| CN104307569A (en) | Heteropoly acid type ionic liquid catalyst as well as preparation and application thereof | |
| CN102001927A (en) | Method for synthesizing iron diacetone | |
| CN101560185A (en) | Method for preparing ethacridine lactate intermediate | |
| CN108499592A (en) | Catalyst for CO2 cycloaddition reaction and preparation method thereof | |
| CN104557978B (en) | A kind of preparation method of cefmetazole sodium | |
| CN105017287A (en) | Preparation method for cephamycin intermediate |
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 | ||
| EE01 | Entry into force of recordation of patent licensing contract |
Application publication date: 20110420 Assignee: Zhejiang Huafang Pharmaceutical Co.,Ltd. Assignor: Zhejiang University of Technology Contract record no.: 2015330000042 Denomination of invention: Method for synthesizing cefdinir Granted publication date: 20121212 License type: Exclusive License Record date: 20150319 |
|
| LICC | Enforcement, change and cancellation of record of contracts on the licence for exploitation of a patent or utility model | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20201217 Address after: Hu bin Zhen Zhai Hao Cun, Boxing County, Binzhou City, Shandong Province Patentee after: SHANDONG CHENGDA NEW ENERGY TECHNOLOGY Co.,Ltd. Address before: Hangzhou City, Zhejiang province 310014 City Zhaohui District Six Patentee before: ZHEJIANG University OF TECHNOLOGY |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20220224 Address after: No. 166, chemical engineering road, economic development zone, Boxing County, Binzhou City, Shandong Province Patentee after: Shandong Xing'an Intelligent Technology Co.,Ltd. Address before: Hu bin Zhen Zhai Hao Cun, Boxing County, Binzhou City, Shandong Province Patentee before: SHANDONG CHENGDA NEW ENERGY TECHNOLOGY Co.,Ltd. |
|
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20121212 |