CN105153198A - Preparation method of ceftibuten - Google Patents
Preparation method of ceftibuten Download PDFInfo
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- CN105153198A CN105153198A CN201510595691.9A CN201510595691A CN105153198A CN 105153198 A CN105153198 A CN 105153198A CN 201510595691 A CN201510595691 A CN 201510595691A CN 105153198 A CN105153198 A CN 105153198A
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- ceftibuten
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- exchange resin
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
- C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
- C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
- C07D501/22—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with radicals containing only hydrogen and carbon atoms, attached in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/02—Preparation
- C07D501/04—Preparation from compounds already containing the ring or condensed ring systems, e.g. by dehydrogenation of the ring, by introduction, elimination or modification of substituents
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Cephalosporin Compounds (AREA)
Abstract
The invention provides a preparation method of ceftibuten. The preparation method comprises the steps of adding cefaclor nucleus, methyltetrahydrofuran and magnesium powder into a reactor, and reacting until the magnesium powder disappears; then, adding a proper quantity of distilled water, stirring, standing for layering, separating out an organic layer, and drying by using anhydrous magnesium sulfate; after filtering, adding D301 week basic ion exchange resin and 2-(2-carbobenzoxy-aminothiazole-4-yl)-5-carbobenzoxy-2-pentenoic acid, and reacting at a certain temperature for a certain time; after ending the reaction, filtering to remove the week basic ion exchange resin; and then, hydrolyzing to obtain a target product, namely ceftibuten. The method is a novel preparation method of ceftibuten, is high in product yield and purity as well as simple and convenient in operation, is a green and clean production process and is suitable for industrial production on a certain scale; and the cefaclor nucleus is a main product in the company, and a sustainable development technology of the company is to prepare ceftibuten serving as a mainly developed variety in the Tenth Five-year Plan period from the product of the company.
Description
Technical field
The invention belongs to field of medicine and chemical technology, particularly relate to a kind of by cefaclor parent nucleus, under D301 type weak base anion-exchange resin catalyst action, prepare the method for Ceftibuten.
Background technology
Ceftibuten (Ceftibuten) is the oral broad-spectrum cephalosporin of the third generation developed by Japanese Yan Yeyi company, stronger anti-microbial effect is had to most of gram negative bacillus and some positive coccus, highly stable to plasmid-mediated β-lactamase, and there is post antibiotic effect; Have that has a broad antifungal spectrum, anti-microbial activity are strong, bioavailability high, be used for the treatment of the various infection caused by sensitive strain, comprise upper respiratory tract infection, lower respiratory infection, the urinary system that oozes infects, enteritis and gastro-enteritis etc.
The chemical name of Ceftibuten is (+)-(6R, 7R)-7 β-[(Z)-2-(2-amino-4-thiazole)-4-carboxyl-2-(Z)-crotonamide]-8-oxygen-5-sulphur-1-nitrogen dicyclo [4.2.0] oct-2-ene-2-carboxylic acid two water thing, structural formula is as shown in formula I:
Ceftibuten now extensively goes on the market in the world wide comprising Japan, is classified as Tenth Five-Year Plan Period focus development kind by China.
At present, three kinds of routes can be divided into according to the preparation of side chain:
(1) with 2-chloracetyl diethyl malonate for raw material, obtained through cyclisation, amido protecting, Michael addition-elimination, alkaline hydrolysis and selective esterification reaction.Although this synthetic route technique is simple, reaction conditions is gentle, be easy to realize suitability for industrialized production, but react starting material 2-chloracetyl diethyl malonate used and chlorine diethyl methylenemalonate is not easily buied, and intermediate reaction relates to hydrolysis, decarboxylation, rearrangement etc., causes whole process reaction yield low;
(2) with 2-chloracetyl acetic acid benzhydryl ester for raw material, obtained through Michael addition-elimination, cyclisation and selective hydrolysis.Although this synthetic route is brief, mild condition, but react raw material 2-chloracetyl acetic acid benzhydryl ester used, 3-carbonyl propionic acid (3-base-2-butylene) ester and carbobenzoxy-(Cbz) thiocarbamide to be difficult to buy, and in reaction process, repeatedly use post separation, cause and answer yield low, treatment capacity is little, does not have practical value;
(3) with 2-amino-4-methylthiazol for raw material, obtained through amido protecting, low temperature conversion, carboxy protective, Michael addition-elimination, Witting reaction and selective hydrolysis etc.This synthetic route reactions steps is long, and overall yield of reaction is low, and reaction conditions requires harsh.
Along with ion-exchange resin technique develop rapidly and in the application of chemical industry, adopt new and effective ion exchange resin as catalyzer, in the research of catalyzed reaction, receive the concern of people, utilize ion exchange resin as catalyzer, swelling due to resin in reaction system, there is the feature of homogeneous catalytic reaction, namely reaction conditions is gentle, and side reaction is few, and selectivity is good, sometimes can up to the degree of Quantitative yield, reaction mechanism and active centre are compared and are easy to illustrate; There is again the feature of heterogeneous catalytic reaction simultaneously, compensate for the deficiency of homogeneous catalysis.Utilize ion exchange resin can heterogeneous catalyst homogeneous phase as catalyzer, to keep original advantage and to make up self deficiency, improve catalytic efficiency, being the promising research direction of in production application process one of homogeneous catalysis and heterogeneous catalyst, is a kind of green chemical synthesis technology.Utilize D301 type ion exchange resin as catalyzer, be that raw material is prepared the method for Ceftibuten there is not been reported by the chloro-3-cephem of cefaclor parent nucleus 7-amino-3--4-carboxylic acid, the synthesis of cephalosporin nucleus 7-ANCA mainly utilizes penicillins and cephalosporins to be prepared as raw material.
Summary of the invention
The object that the present invention will solve is to provide a kind of novel process of green syt Ceftibuten, by selecting D301 type ion exchange resin as catalyzer, utilizes cefaclor parent nucleus to prepare Ceftibuten for raw material.This technology is a Green Chemistry technology of preparing easy and simple to handle and eco-friendly, takes full advantage of the homegrown resource of company, is the technology of company's Sustainable development.
For achieving the above object, the present invention adopts following technical scheme:
A kind of preparation method of Ceftibuten, comprise and add cefaclor parent nucleus (II) in reactor, methyltetrahydrofuran and magnesium powder, react after disappearing to magnesium powder, add appropriate distilled water, stir, stratification, separate methyltetrahydrofuran organic over anhydrous dried over mgso, after filtration, add weak-base ion-exchange resin (III) and 2-(2-benzyloxycarbonyl amino thiazole-4-yl)-5-carbobenzoxy-(Cbz)-2-pentenoic acid, react under certain temperature and time, after reaction terminates, filtering weak-base ion-exchange resin, the obtained target product Ceftibuten of hydrolysis again,
Wherein, R in formula III
1, R
2respective is independently methyl or hydrogen atom, and n represents the polymerization degree, the number of times that namely in molecule, basic structure repeats.If the mixture of the homologue that same chemical constitution and the polymerization degree do not wait, then n is the mean polymerisation degree of this mixture, i.e. the mean value of the polymerization degree.
Weak-base ion-exchange resin of the present invention is commercially available prod, described weak-base ion-exchange resin (III) is D301RStyrene-DVB, one in D301TStyrene-DVB, D301GStyrene-DVB, D392Styrene-DVB or D380Styrene-DVB.
The temperature of reaction added in the reactions steps of weak-base ion-exchange resin (III) described in the present invention is 5 ~ 50 DEG C, preferably 10 ~ 30 DEG C; Reaction times is 1 ~ 10 hour, preferably 3 ~ 5 hours.
The quality consumption of described weak-base ion-exchange resin (III) catalyzer is 10 ~ 50% of cephalosporin nucleus quality consumption, preferably 20 ~ 30%.
Hydrolysis reaction described in the present invention distills the reaction solution filtering out weak-base ion-exchange resin (III), removing methyltetrahydrofuran, then Virahol, NaOH solution is added under room temperature, be warming up to 20 ~ 50 DEG C of reactions 1 ~ 5 hour, be then cooled to 20 DEG C, then use dichloromethane extraction, obtain aqueous layer and adjust pH=5 ~ 6 at 0 DEG C with dense HCl, leave standstill crystallization, filter, dry target product.
Compared with prior art, its Advantages found exists in the present invention:
1. utilize weak-base ion-exchange resin (III) as catalyzer, be that to prepare Ceftibuten be a new preparation method to raw material by cefaclor parent nucleus, its yield is high, purity is high, easy and simple to handle, be the production technique that a green cleans, be suitable for the suitability for industrialized production of certain scale;
2. cefaclor parent nucleus is our company's main product, and utilizing the product of our company to prepare Tenth Five-Year Plan Period focus development kind Ceftibuten is the technology of our company's Sustainable development.
Embodiment
Below in conjunction with specific embodiment, the invention will be further described, but protection scope of the present invention is not limited to this.
Embodiment 1
In 100 milliliters of there-necked flasks, add cefaclor parent nucleus 2.4 grams (0.01 mole), methyltetrahydrofuran 15 milliliters, 0.4 gram, magnesium powder (0.017 mole), after 30 DEG C of reactions to magnesium powder disappears, add distilled water 10 milliliters, stir 10 minutes, stratification, separate methyltetrahydrofuran organic over anhydrous dried over mgso, after filtration, add Styrene-DVB (D301R) resin 0.7 gram, 2-(2-benzyloxycarbonyl amino thiazole-4-yl)-5-carbobenzoxy-(Cbz)-2-pentenoic acid 5 grams (0.011 mole), 30 DEG C of reactions 3 hours, reaction terminates filtering Styrene-DVB (D301R) resin, distillation removing methyltetrahydrofuran, 20 DEG C add different Virahol 10 milliliters, NaOH (30%) aqueous solution 20 milliliters, 30 DEG C of reactions 1 hour, be cooled to 20 DEG C.With methylene dichloride 10 × 3 milliliters extraction three times, aqueous layer drips dense HCl at 0 DEG C and adjusts pH=5 ~ 6, leaves standstill crystallization, filters, dry target product Ceftibuten (I) 3.55 gram, yield 86.7%, HPLC:98.5%.Fusing point: 178 ~ 181 DEG C.HRMS(ESI)：m/e＝410(M
+)。IR(KBr)cm
-1：3574，3247，3051，2957，1771，1699，1651，1544，1364，1255。
Embodiment 2
In 100 milliliters of there-necked flasks, add cefaclor parent nucleus 2.4 grams (0.01 mole), methyltetrahydrofuran 15 milliliters, 0.4 gram, magnesium powder (0.017 mole), after 50 DEG C of reactions to magnesium powder disappears, add distilled water 10 milliliters, stir 10 minutes, stratification, separate methyltetrahydrofuran organic over anhydrous dried over mgso, after filtration, add Styrene-DVB (D301R) resin 1.2 grams, 2-(2-benzyloxycarbonyl amino thiazole-4-yl)-5-carbobenzoxy-(Cbz)-2-pentenoic acid 5 grams (0.011 mole), 30 DEG C of reactions 1 hour, reaction terminates filtering Styrene-DVB (D301R) resin, distillation removing methyltetrahydrofuran, 30 DEG C add different Virahol 10 milliliters, NaOH (30%) aqueous solution 20 milliliters, 30 DEG C of reactions 1 hour, be cooled to 20 DEG C.With methylene dichloride 10 × 3 milliliters extraction three times, aqueous layer drips dense HCl at 0 DEG C and adjusts pH=5 ~ 6, leaves standstill crystallization, filters, dry target product Ceftibuten (I) 3.57 gram, yield 86.9%, HPLC:99.0%.
Embodiment 3
In 100 milliliters of there-necked flasks, add cefaclor parent nucleus 2.4 grams (0.01 mole), methyltetrahydrofuran 15 milliliters, 0.4 gram, magnesium powder (0.017 mole), after 30 DEG C of reactions to magnesium powder disappears, add distilled water 10 milliliters, stir 10 minutes, stratification, separate methyltetrahydrofuran organic over anhydrous dried over mgso, after filtration, add Styrene-DVB (D301T) resin 0.7 gram, 2-(2-benzyloxycarbonyl amino thiazole-4-yl)-5-carbobenzoxy-(Cbz)-2-pentenoic acid 5 grams (0.011 mole), 10 DEG C of reactions 3 hours, reaction terminates filtering Styrene-DVB (D301T) resin, distillation removing methyltetrahydrofuran, 20 DEG C add different Virahol 10 milliliters, NaOH (30%) aqueous solution 20 milliliters, 20 DEG C of reactions 1 hour, with methylene dichloride 10 × 3 milliliters extraction three times, aqueous layer drips dense HCl at 0 DEG C and adjusts pH=5 ~ 6, leave standstill crystallization, filter, dry target product Ceftibuten (I) 3.56 gram, yield 86.8%, HPLC:99.1%.
Embodiment 4
In 100 milliliters of there-necked flasks, add cefaclor parent nucleus 2.4 grams (0.01 mole), methyltetrahydrofuran 15 milliliters, 0.4 gram, magnesium powder (0.017 mole), after 30 DEG C of reactions to magnesium powder disappears, add distilled water 10 milliliters, stir 10 minutes, stratification, separate methyltetrahydrofuran organic over anhydrous dried over mgso, after filtration, add Styrene-DVB (D301G) resin 0.3 gram, 2-(2-benzyloxycarbonyl amino thiazole-4-yl)-5-carbobenzoxy-(Cbz)-2-pentenoic acid 5 grams (0.011 mole), 30 DEG C of reactions 3 hours, reaction terminates filtering Styrene-DVB (D301G) resin, distillation removing methyltetrahydrofuran, 20 DEG C add different Virahol 10 milliliters, NaOH (30%) aqueous solution 20 milliliters, 10 DEG C of reactions 1 hour, with methylene dichloride 10 × 3 milliliters extraction three times, aqueous layer drips dense HCl at 0 DEG C and adjusts pH=5 ~ 6, leave standstill crystallization, filter, dry target product Ceftibuten (I) 3.50 gram, yield 85.3%, HPLC:99.2%.
Embodiment 5
In 100 milliliters of there-necked flasks, add cefaclor parent nucleus 2.4 grams (0.01 mole), methyltetrahydrofuran 15 milliliters, 0.4 gram, magnesium powder (0.017 mole), after 30 DEG C of reactions to magnesium powder disappears, add distilled water 10 milliliters, stir 10 minutes, stratification, separate methyltetrahydrofuran organic over anhydrous dried over mgso, after filtration, add Styrene-DVB (D392) resin 0.7 gram, 2-(2-benzyloxycarbonyl amino thiazole-4-yl)-5-carbobenzoxy-(Cbz)-2-pentenoic acid 5 grams (0.011 mole), 30 DEG C of reactions 3 hours, reaction terminates filtering Styrene-DVB (D392) resin, distillation removing methyltetrahydrofuran, 20 DEG C add different Virahol 10 milliliters, NaOH (30%) aqueous solution 20 milliliters, 30 DEG C of reactions 1 hour, be cooled to 20 DEG C.With methylene dichloride 10 × 3 milliliters extraction three times, aqueous layer drips dense HCl at 0 DEG C and adjusts pH=5 ~ 6, leaves standstill crystallization, filters, dry target product Ceftibuten (I) 3.57 gram, yield 87.1%, HPLC:98.6%.
Claims (7)
1. the preparation method of a Ceftibuten, it is characterized in that comprising and add cefaclor parent nucleus (II) in reactor, methyltetrahydrofuran and magnesium powder, react after disappearing to magnesium powder, add appropriate distilled water, stir, stratification, separate methyltetrahydrofuran organic over anhydrous dried over mgso, after filtration, add weak-base ion-exchange resin (III) and 2-(2-benzyloxycarbonyl amino thiazole-4-yl)-5-carbobenzoxy-(Cbz)-2-pentenoic acid, react under certain temperature and time, after reaction terminates, filtering weak-base ion-exchange resin, the obtained target product Ceftibuten of hydrolysis again,
Wherein, R in formula III
1, R
2respective is independently methyl or hydrogen atom, and n represents the polymerization degree.
2. the preparation method of Ceftibuten according to claim 1, it is characterized in that the described temperature of reaction added in the reactions steps of weak-base ion-exchange resin (III) is 5 ~ 50 DEG C, the reaction times is 1 ~ 10 hour.
3. the preparation method of Ceftibuten according to claim 2, is characterized in that temperature of reaction is 10 ~ 30 DEG C; Reaction times is 3 ~ 5 hours.
4. the preparation method of Ceftibuten according to claim 1, is characterized in that the quality consumption of described weak-base ion-exchange resin catalyzer (III) is 10 ~ 50% of cephalosporin nucleus quality consumption.
5. the preparation method of Ceftibuten according to claim 4, is characterized in that the quality consumption of described weak-base ion-exchange resin catalyzer (III) is 20 ~ 30% of cephalosporin nucleus quality consumption.
6. according to the preparation method of the arbitrary described Ceftibuten of claim 1 to 5, it is characterized in that described weak-base ion-exchange resin (III) is D301RStyrene-DVB, D301TStyrene-DVB, one in D301GStyrene-DVB, D392Styrene-DVB or D380Styrene-DVB.
7. the preparation method of Ceftibuten according to claim 1, it is characterized in that described hydrolysis reaction distills the reaction solution filtering out weak-base ion-exchange resin, removing methyltetrahydrofuran, then adds Virahol, NaOH solution under room temperature, be warming up to 20 ~ 50 DEG C of reactions 1 ~ 5 hour, then 20 DEG C are cooled to, use dichloromethane extraction again, obtain aqueous layer and adjust pH=5 ~ 6 at 0 DEG C with dense HCl, leave standstill crystallization, filter, dry target product.
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106397457A (en) * | 2016-09-21 | 2017-02-15 | 临沂草之美医药科技有限公司 | Drug ceftibuten crystal compound for treating surgical operation infection |
| CN106397455A (en) * | 2016-08-30 | 2017-02-15 | 山东罗欣药业集团恒欣药业有限公司 | Anti-infective drug ceftibuten crystal compound and composition thereof |
| CN106397454A (en) * | 2016-08-30 | 2017-02-15 | 山东罗欣药业集团股份有限公司 | Anti-infective drug--ceftibuten crystal form compound and composition thereof |
| CN106432272A (en) * | 2016-09-21 | 2017-02-22 | 临沂草之美医药科技有限公司 | Method for preparing drug ceftibuten crystal compound for treating surgical operation infection |
| CN106420617A (en) * | 2016-09-21 | 2017-02-22 | 临沂草之美医药科技有限公司 | Medicine ceftibuten powder injection for treating surgical infection |
| CN106432271A (en) * | 2016-09-21 | 2017-02-22 | 临沂草之美医药科技有限公司 | Pharmaceutical ceftibuten crystal compound for treating surgical infection |
| CN106432270A (en) * | 2016-09-21 | 2017-02-22 | 临沂草之美医药科技有限公司 | Method for preparing medicine ceftibuten crystal compound for treating surgical infection |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1178220A (en) * | 1996-10-02 | 1998-04-08 | 大化学株式会社 | Process for producing cefazolin |
| CN101186566A (en) * | 2007-11-23 | 2008-05-28 | 浙江工业大学 | Method for preparing acetylacetone by using D301 type alkalescent anion exchange resin as catalyst |
| CN101186602A (en) * | 2007-11-28 | 2008-05-28 | 浙江工业大学 | Method for synthesizing 2-methyl-2-aryl-1,3-dioxolane compound |
-
2015
- 2015-09-17 CN CN201510595691.9A patent/CN105153198B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1178220A (en) * | 1996-10-02 | 1998-04-08 | 大化学株式会社 | Process for producing cefazolin |
| CN101186566A (en) * | 2007-11-23 | 2008-05-28 | 浙江工业大学 | Method for preparing acetylacetone by using D301 type alkalescent anion exchange resin as catalyst |
| CN101186602A (en) * | 2007-11-28 | 2008-05-28 | 浙江工业大学 | Method for synthesizing 2-methyl-2-aryl-1,3-dioxolane compound |
Non-Patent Citations (2)
| Title |
|---|
| ERMANNO BERNASCONI,ET AL.: "Ceftibuten: Development of a Commercial Process Based on Cephalosporin C. Part III. Process for the Conversion of 3-Exomethylene-7(R)-glutaroylaminocepham-4-carboxylic Acid 1(S)-Oxide to Ceftibuten", 《ORGANIC PROCESS RESEARCH & DEVELOPMENT》 * |
| 伍越寰，等: "《有机化学》", 30 September 2002 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106397455A (en) * | 2016-08-30 | 2017-02-15 | 山东罗欣药业集团恒欣药业有限公司 | Anti-infective drug ceftibuten crystal compound and composition thereof |
| CN106397454A (en) * | 2016-08-30 | 2017-02-15 | 山东罗欣药业集团股份有限公司 | Anti-infective drug--ceftibuten crystal form compound and composition thereof |
| CN106397457A (en) * | 2016-09-21 | 2017-02-15 | 临沂草之美医药科技有限公司 | Drug ceftibuten crystal compound for treating surgical operation infection |
| CN106432272A (en) * | 2016-09-21 | 2017-02-22 | 临沂草之美医药科技有限公司 | Method for preparing drug ceftibuten crystal compound for treating surgical operation infection |
| CN106420617A (en) * | 2016-09-21 | 2017-02-22 | 临沂草之美医药科技有限公司 | Medicine ceftibuten powder injection for treating surgical infection |
| CN106432271A (en) * | 2016-09-21 | 2017-02-22 | 临沂草之美医药科技有限公司 | Pharmaceutical ceftibuten crystal compound for treating surgical infection |
| CN106432270A (en) * | 2016-09-21 | 2017-02-22 | 临沂草之美医药科技有限公司 | Method for preparing medicine ceftibuten crystal compound for treating surgical infection |
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Effective date of registration: 20190117 Address after: 261313 No. 1 Sifang Road, Xiaying Economic Development Zone, Changyi City, Weifang City, Shandong Province Patentee after: Shandong Changyi Sifang Pharmaceutical Chemical Co., Ltd. Address before: 318020 No. 10 Dazhalu Road, Jiangkou Economic Development Zone, Huangyan District, Taizhou City, Zhejiang Province Co-patentee before: Pei Wen Patentee before: ZHEJIANG HUAFANG PHARMACEUTICAL CO., LTD. |