CN102020664A - Synthesis method for cefdinir - Google Patents
Synthesis method for cefdinir Download PDFInfo
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- CN102020664A CN102020664A CN 201010567721 CN201010567721A CN102020664A CN 102020664 A CN102020664 A CN 102020664A CN 201010567721 CN201010567721 CN 201010567721 CN 201010567721 A CN201010567721 A CN 201010567721A CN 102020664 A CN102020664 A CN 102020664A
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- cefdinir
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- base catalyst
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- 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 abstract description 4
- 239000007787 solid Substances 0.000 claims abstract description 36
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 30
- 238000006243 chemical reaction Methods 0.000 claims abstract description 27
- 239000003054 catalyst Substances 0.000 claims abstract description 21
- 239000002608 ionic liquid Substances 0.000 claims abstract description 19
- 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 14
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000012346 acetyl chloride Substances 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims abstract description 8
- 230000007062 hydrolysis Effects 0.000 claims abstract description 5
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 5
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 27
- 239000002585 base Substances 0.000 claims description 23
- 238000000605 extraction Methods 0.000 claims description 15
- 239000007788 liquid Substances 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- 239000003513 alkali Substances 0.000 claims description 12
- 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 9
- 239000005457 ice water Substances 0.000 claims description 9
- 239000001117 sulphuric acid Substances 0.000 claims description 9
- 235000011149 sulphuric acid Nutrition 0.000 claims description 9
- 238000010189 synthetic method Methods 0.000 claims description 9
- 238000001035 drying Methods 0.000 claims description 8
- 230000000694 effects Effects 0.000 claims description 5
- 229920002401 polyacrylamide Polymers 0.000 claims description 5
- 206010013786 Dry skin Diseases 0.000 claims description 3
- 239000000284 extract Substances 0.000 claims description 3
- 238000001125 extrusion Methods 0.000 claims description 3
- 238000000227 grinding Methods 0.000 claims description 3
- 238000013019 agitation Methods 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 238000005406 washing Methods 0.000 claims description 2
- 238000010979 pH adjustment Methods 0.000 claims 1
- 238000005516 engineering process Methods 0.000 abstract description 9
- 230000020477 pH reduction Effects 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 238000006555 catalytic reaction Methods 0.000 description 3
- 238000002360 preparation method 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
- 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
- 230000007613 environmental effect Effects 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
- 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
- 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
- 150000001875 compounds Chemical class 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
- 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
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
Landscapes
- Cephalosporin Compounds (AREA)
Abstract
The invention discloses a synthesis method for cefdinir. The method comprises the following steps of: reacting 7-amino-3-vinyl-3-cephem-4-carboxylic acid shown in a formula (I) and 2-(2-aminothiazole-4-yl)-2-(Z)-(acetoxyimido)acetyl chloride shown in a formula (II) at the temperature of between 10 and 60 DEG C under the action of solid base catalyst in the alkaline ionic liquid shown in a formula (III); and after the reaction is completed, performing hydrolysis and acidification to obtain cefdinir hydrochloride shown in a formula (IV). The technology is easy to operate, less in three wastes, and convenient for post treatment, the ionic liquid and solid base can be reused, and the technology is economical and practical environmentally-friendly technology.
Description
(1) technical field
The present invention relates to a kind of synthetic 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.American Pharmacopeia recorded in 1998 in advance.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 steps 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 is in a liquid state under room temperature and adjacent temperature.Ionic liquid has the incomparable advantage of many other materials, as the liquid temperature wide ranges, does not have significant vapour pressure, Heat stability is good, its acid-basicity can carry out modulation as required, and many mineral compound and organic compound 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, have the easy and isolating advantage of product of homogeneous catalyst high reaction activity and heterogeneous catalyst simultaneously concurrently, have broad application prospects in organic synthesis industry, 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 to be solved in the present invention provides a kind of novel synthesis of Cefdinir, utilize alkali ionic liquid as reaction medium and solid alkali as catalyzer, by 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 synthetic 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., react under 10～60 ℃ 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 made 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 polyacrylamide, 5～15 parts in water; Described solid base catalyst prepares by the following method: with each component mixed grinding after 0.5～5 hour, extrusion molding, dried 0.5～10 hour down in infrared lamp, then in 50～200 ℃ of dryings 1～10 hour, at last in 300～600 ℃ of roastings 1～6 hour, cooling, drying get described 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 described 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 described 7-amino-3-vinyl-3-cephem-4-carboxylic acid and described alkali ionic liquid is 1: 5～10.
Further, the mass ratio that feeds intake of described solid base catalyst and 7-amino-3-vinyl-3-cephem-4-carboxylic acid is 30～50%: 1.
Further, described solid base catalyst is preferably made by the following component of quality proportioning: γ-Al
2O
3100 parts, Mg (OH)
210 parts, Ca (OH)
20.5 part, 3 parts of polyacrylamides, 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 extracts with toluene, and ionic liquid in the reaction system and solid alkali can be directly used in and continue reaction.Adding sulphuric acid soln in the extraction liquid is 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
The present invention is described further below in conjunction with specific embodiment, but protection scope of the present invention is not limited in this.
The preparation of solid alkali:
Make by the component that the quality proportioning is following: γ-Al
2O
3100 parts, Mg (OH)
210 parts, Ca (OH)
20.5 part, 3 parts of polyacrylamides, 10 parts in water.
The preparation method: with each component mixed grinding after 1 hour, extrusion molding, in infrared lamp oven dry 5 hours down, then in 110 ℃ of dryings 5 hours, at last in 500 ℃ of roastings 3 hours, cooling, drying, described 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 methyl butyl imidazoles subsalt ionic liquid 2.3g, solid base catalyst 0.07g adds in the reactor, reacts 5 hours down at 50 ℃, and reaction finishes, 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, transfer 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, separate out faint yellow solid, filter, wash with ether, 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 add in the reactor, react 0.5 hour down at 60 ℃, reaction finishes, reaction solution is with toluene 5 * 3mL extraction, adds 30% sulphuric acid soln with volume in the extraction liquid, stirring at room 2 hours, add saturated sodium bicarbonate solution again, transfer pH=6.5, stirring at room 30 minutes is filtered and is told insolubles, 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, 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 add in the reactor, react 5 hours down at 10 ℃, reaction finishes, reaction solution is with toluene 5 * 3mL extraction, adds 30% sulphuric acid soln with volume in the extraction liquid, stirring at room 2 hours, add saturated sodium bicarbonate solution again, transfer pH=6.5, stirring at room 30 minutes is filtered and is told insolubles, 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, 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 add in the reactor, react 2 hours down at 30 ℃, reaction finishes, reaction solution is with toluene 5 * 3mL extraction, adds 30% sulphuric acid soln with volume in the extraction liquid, stirring at room 2 hours, add saturated sodium bicarbonate solution again, transfer pH=6.5, stirring at room 30 minutes is filtered and is told insolubles, 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, 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), methyl butyl imidazoles hexafluorophosphate ionic liquid 2g, solid base catalyst 0.12g add in the reactor, react 2 hours down at 30 ℃, reaction finishes, reaction solution is with toluene 5 * 3mL extraction, adds 30% sulphuric acid soln with volume in the extraction liquid, stirring at room 2 hours, add saturated sodium bicarbonate solution again, transfer pH=6.5, stirring at room 30 minutes is filtered and is told insolubles, 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, 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 add in the reactor, react 5 hours down at 50 ℃, reaction finishes, reaction solution is with toluene 5 * 3mL extraction, adds 30% sulphuric acid soln with volume in the extraction liquid, stirring at room 2 hours, add saturated sodium bicarbonate solution again, transfer pH=5.5, stirring at room 30 minutes is filtered and is told insolubles, separatory is told water, hydrochloric acid with 10% under the ice-water bath cooling is transferred pH=2, separates out faint yellow solid, filters, 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 add in the reactor, react 5 hours down at 50 ℃, reaction finishes, reaction solution is with toluene 5 * 3mL extraction, adds 30% sulphuric acid soln with volume in the extraction liquid, stirring at room 2 hours, add saturated sodium bicarbonate solution again, transfer pH=7, stirring at room 30 minutes is filtered and is told insolubles, separatory is told water, hydrochloric acid with 10% under the ice-water bath cooling is transferred pH=5, separates out faint yellow solid, filters, wash with ether, dry Cefdinir hydrochloride product 0.35g, yield 83%, the purity 99.5% of getting.
Claims (6)
1. the synthetic method of a 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., react under 10～60 ℃ 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 made 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 polyacrylamide, 5～15 parts in water; Described solid base catalyst prepares by the following method: with each component mixed grinding after 0.5～5 hour, extrusion molding, dried 0.5～10 hour down in infrared lamp, then in 50～200 ℃ of dryings 1～10 hour, at last in 300～600 ℃ of roastings 1～6 hour, cooling, drying get described 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 -
2. the synthetic method of Cefdinir as claimed in claim 1 is characterized in that the amount of substance ratio that feeds intake of described 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.
3. the synthetic method of Cefdinir as claimed in claim 1 is characterized in that the mass ratio that feeds intake of described 7-amino-3-vinyl-3-cephem-4-carboxylic acid and described alkali ionic liquid is 1: 5～10.
4. the synthetic method of Cefdinir as claimed in claim 1 is characterized in that the mass ratio that feeds intake of described solid base catalyst and 7-amino-3-vinyl-3-cephem-4-carboxylic acid is 30～50%: 1.
5. as the synthetic method of the described Cefdinir of one of claim 1～4, it is characterized in that described solid base catalyst made by the following component of quality proportioning: γ-Al
2O
3100 parts, Mg (OH)
210 parts, Ca (OH)
20.5 part, 3 parts of polyacrylamides, 10 parts in water.
6. as the synthetic method of the described Cefdinir of one of claim 1～4, it is characterized in that described hydrolysis, acidifying specifically carry out according to following steps: reaction finishes, and reaction solution extracts with toluene, adds sulphuric acid soln in the extraction liquid and is hydrolyzed, add lye pH adjustment to 5.5～7.5 then, agitation and filtration is told water, transfers pH to 1～5 with hydrochloric acid under the ice-water bath cooling, separate out faint yellow solid, filter, washing, drying obtains the Cefdinir hydrochloride shown in the formula (IV).
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Cited By (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 |
| CN105481782A (en) * | 2015-12-25 | 2016-04-13 | 浙江工业大学 | Preparation method of sulfaquinoxaline |
| CN107286148A (en) * | 2017-06-20 | 2017-10-24 | 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 |
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| 《合成化学》 20011231 林桂椿等 头孢地尼的合成 383-385 1-6 第9卷, 第5期 2 * |
| 《绿色化学》 20081231 贡长生 第二章 绿色化学原理 华中科技大学出版社 第32-34、38-40页 1-6 , 1 * |
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| 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 |
| CN105481782A (en) * | 2015-12-25 | 2016-04-13 | 浙江工业大学 | Preparation method of sulfaquinoxaline |
| CN105481782B (en) * | 2015-12-25 | 2018-05-08 | 浙江工业大学 | A kind of preparation method of sulfaquinoxaline |
| CN107286148A (en) * | 2017-06-20 | 2017-10-24 | 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 |
| 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 |
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| CN102020664B (en) | 2012-12-12 |
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