CN101891666A - Preparation method of intermediate of beta methylcarbapenem antibiotics - Google Patents
Preparation method of intermediate of beta methylcarbapenem antibiotics Download PDFInfo
- Publication number
- CN101891666A CN101891666A CN 201010232089 CN201010232089A CN101891666A CN 101891666 A CN101891666 A CN 101891666A CN 201010232089 CN201010232089 CN 201010232089 CN 201010232089 A CN201010232089 A CN 201010232089A CN 101891666 A CN101891666 A CN 101891666A
- Authority
- CN
- China
- Prior art keywords
- reaction
- compound
- preparation
- formula
- solution
- 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.)
- Granted
Links
Landscapes
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cephalosporin Compounds (AREA)
Abstract
The invention provides a preparation method of an intermediate of beta-methylcarbapenem antibiotics, which comprises the following steps: (1) under inert-gas protection, adding an organic solvent and a compound III (or a solution containing the compound III) to a reactor, adding a diazotized reagent and organic base, controlling the reaction temperature, and monitoring the reaction by TLC or HPLC; (2) after the reaction, without any post treatment, adding a certain amount of alcohol, adding acid fluid, controlling the temperature of the reaction system when the acid is added, after adding the acid, controlling the reaction temperature, and monitoring the reaction by TLC or HPLC; and (3) after the reaction of step (2), respectively washing the reaction fluid with water or brine, water containing soda and the like for multiple times, discarding the water phase, and crystallizing to obtain the target product compound I. The invention has simple operation, the solution containing the intermediate (compound IV) does not need post treatment, separation or purification for reaction of the next step, and the raw materials completely react and have few impurities and high product yield.
Description
Technical field
The present invention relates to a kind of synthetic method of beta-methyl carbapenem antibiotic, relate in particular to a kind of synthetic method of beta-methyl carbapenem antibiotic intermediate.
Background technology
Carbapenem antibiotic is a kind of novel complete synthesis β-Nei Xiananleikangshengsu, and gram-positive microorganism and negative bacterium, aerophil, anerobe are all had very strong anti-microbial activity.Since 1976 found sulfomycin, the research of carbapenem antibiotic had had very big development.Particularly 1 beta-methyl carbapenem antibiotic has good chemical stability, stable to β-Nei Xiananmei and kidney dehydrogenation peptide-I enzyme, is one of choice drug for the treatment of at present severe and multi-drug resistant bacteria infection, in the clinical usefulness more and more widely that obtained.
Commercial at present 1 beta-methyl carbapenem antibiotic has meropenem, biapenem, S-4661 and ertapenem.Meropenem is that first is applied to 1 clinical Beta-methyl carbapenem antibiotic.
With the compound III is raw material synthetic compound I, at present the synthetic method of the disclosed report of patent documentation all needed through two steps: the first step is to carry out deprotection (in the reaction formula by compound III synthetic compound II) earlier, reaction solution is carried out aftertreatment, purifying (normally crystallization or use column chromatography purification); Second one is to carry out diazotization (in the reaction formula by Compound I I synthetic compound I), and reaction solution is carried out aftertreatment, purifying (normally crystallization or use column chromatography purification).Reaction formula is as follows:
So substep operate time-consuming, take equipment, reduced the ultimate yield of product, production cost improves, simultaneously also inevitably fecund give birth to " three wastes " such as waste water, waste residue, waste gas and bring environmental pollution.
The applicant discloses in CN200610057578.6, CN200610083362.7 and has adopted the method for the treatment of different things alike to carry out above-mentioned reaction, the solution that contains intermediates need not to carry out aftertreatment, separation, also need not carry out purifying promptly carries out next step reaction, greatly reduces production cost and three-waste pollution.But because deprotection reaction is to carry out under acidic conditions, and acidic conditions is disadvantageous to follow-up diazotization, so the reaction soln of III-II must carry out more loaded down with trivial details aftertreatment, and just the step is sent out and answers down.Thereby former process efficiency is high not enough.
Summary of the invention
At the deficiencies in the prior art, the invention provides a kind of beta-methyl carbapenem antibiotic intermediates preparation, its core is to carry out earlier diazotization reaction, deprotection then.This preparation method can simplify technological operation effectively.
In the present invention, in order to narrate conveniently, molecular formula is that the compound of I is called for short " Compound I " or " formula (I) compound ", and other compound is described roughly the same.
In the present invention, each abbreviation is expressed as follows: PNB represents the p-nitrophenyl methyl; TBDMS represents tertiary butyl dimethylsilyl; TLC represents thin-layer chromatography; HPLC represents high performance liquid chromatography.
Preparation method provided by the present invention can may further comprise the steps:
1) formula (III) compound is reacted under the effect of diazo reagent, obtain comprising the reaction solution of formula (IV) compound;
2) with formula (IV) compound deprotection base, obtain comprising the solution of formula (I) compound,
Reaction scheme is as follows:
In preferred implementation of the present invention, method of the present invention can may further comprise the steps:
(1) under protection of inert gas, organic solvent and the compound III solution of compound III (or contain) are joined in the reactor, add diazo reagent and organic bases, control temperature of reaction well, TLC or HPLC monitoring reaction;
(2) reaction finishes, and need not to carry out any aftertreatment, adds a certain amount of alcohol, adds acid solution, and control acid adds the temperature of fashionable reaction system, controls thermotonus after acid finishes well, TLC or HPLC monitoring reaction;
(3) reaction finishes, and respectively with water or salt solution, buck etc. are washing reaction liquid repeatedly, abandons water;
(4) crystallization: organic phase concentrates, and adds recrystallisation solvent, and stirred crystallization is filtered at a certain temperature, and drying had both got the target product Compound I.
In above-mentioned steps (1), rare gas element is generally argon gas or nitrogen.
In above-mentioned steps (1), organic solvent is meant acetonitrile, tetrahydrofuran (THF), dimethyl formamide, diethylformamide, dioxane, ethyl acetate, methyl acetate, propyl acetate, butylacetate, one or more of methyl alcohol, ethanol, n-propyl alcohol, Virahol, acetone, butanone etc., preferred acetonitrile, tetrahydrofuran (THF), dimethyl formamide, diethylformamide, dioxane, ethyl acetate, acetone.
In above-mentioned steps (1), " solution that contains compound III " is meant by disclosing the solution that contains compound III that known synthetic method obtains.
In above-mentioned steps (1), adding diazo reagent and organic bases is meant: diazo reagent comprises sulfonyl azide, methylsulfonyl nitrine, tolylsulfonyl nitrine, to carboxyl sulfonyl azide, dodecyl sulfonyl azide etc., preferred dodecyl sulfonyl azide etc.; Organic bases is meant substituent pyridine, N-methyl piperidine, N-methylmorpholine, aniline, methylphenylamine, N on Trimethylamine 99, dimethylamine, triethylamine, diethylamine, Tributylamine, dibutylamine, trioctylamine, Di-Octyl amine, di ethamine, diisopropylethylamine, diisopropylamine, di-n-propyl amine, pyridine or the pyridine ring, one or more of accelerine etc., preferred triethylamine, diisopropylethylamine, diisopropylamine, Tributylamine, 2,5-lutidine, 3,5-lutidine etc.
In above-mentioned steps (1), diazo reagent and organic bases both can add separately also can mix the back adding.
In above-mentioned steps (1), temperature of reaction is controlled at-40～45 ℃, preferred-20～25 ℃.
In above-mentioned steps (2), alcohol is meant alcohol, particular methanol and an ethanol to four carbon atom.
In above-mentioned steps (2), acid solution is meant the aqueous solution of strong acid such as hydrochloric acid, Hydrogen bromide, sulfuric acid, nitric acid, trifluoroacetic acid, tosic acid, and concentration is controlled at 0.5～12mol.l usually
-1, the add-on control deprotection reaction of acid can be finished in 10 hours to good; Also can use the Acetyl Chloride 98Min. and the propionyl chloride of catalytic amount to replace acid solution to carry out deprotection.
In above-mentioned steps (2), relieving haperacidity adds the temperature of fashionable reaction system and should be advisable to be no more than 60 ℃.
In above-mentioned steps (3), salt solution is meant the aqueous solution of sodium-chlor, Repone K, sodium sulfate, vitriolate of tartar etc., preferred sodium chloride aqueous solution.
In above-mentioned steps (3), buck is meant the aqueous solution of yellow soda ash, salt of wormwood, sodium bicarbonate, saleratus, Sodium phosphate dibasic, dipotassium hydrogen phosphate, sodium hydroxide, potassium hydroxide etc.; Concentration is 1～20%.
In above-mentioned steps (4), recrystallisation solvent is meant sherwood oil, ether, hexanaphthene, pentamethylene, normal heptane, the organic solvent that the normal hexane isopolarity is lower.
In above-mentioned steps (4), Tc is controlled at-40～35 ℃ usually, preferred-40～25 ℃.
The invention has the advantages that:
1) whole technological operation solution easy, that contain intermediates (compound IV) need not to carry out aftertreatment, separation, also need not carry out purifying and can carry out next step reaction;
2) compare with disclosed method among applicant patent CN200610057578.6, the CN200610083362.7 before, technological operation is simplified, and raw material reaction is complete, product yield is high, has also reduced the environmental pollution that " three wastes " bring simultaneously.
In with the lower section, set forth the specific embodiment of the present invention, yet these embodiment also limit protection scope of the present invention never in any form by a plurality of preferred embodiments.
Embodiment
Material therefor in following examples if no special instructions, is commercially available purchase product.
Embodiment 1
Under protection of inert gas; with 400ml ethyl acetate and 60.0g compound III (i.e. (3S; 4R)-3-[(1R)-the 1-tert-butyl dimethyl silica ethyl]-4-[(1R)-1-methyl-3-PNB oxygen carbonyl-2-ketone group propyl group]-heterocyclic fourth-2-ketone; by patent ZL200610083362.7 disclosed method preparation) solid join in the reactor; the triethylamine that adds 64.0g dodecyl sulfonyl azide and 15.0g; be controlled at reaction about-10 ℃; TLC or HPLC monitoring reaction; reaction finishes; the methyl alcohol of 200ml will be added in the reaction solution that obtain; the concentrated hydrochloric acid that adds 120ml; temperature control is in reaction below 35 ℃; TLC or HPLC monitoring reaction; the reaction solution that obtains is used the 400ml saturated brine successively; the wet chemical of 400ml5%; 400ml saturated brine repetitive scrubbing; abandon water; the anhydrous sodium sulfate dehydration drying that adds 100g in the organic phase; filter; filtrate decompression concentrates; add the 150g sherwood oil in the concentrated solution; 35 ℃ of following stirred crystallization; filter, filtration cakes torrefaction gets 46.5g target compound (Compound I).Mass yield 76.00%.
Compound I be known substance and the retention time of this compound in HPLC and
1H NMR spectrum is with to have article now consistent.
Embodiment 2
Under protection of inert gas; the ethyl acetate solution (this solution is by the preparation of patent ZL200610083362.7 disclosed method) that will contain the 60.0g compound III joins in the reactor; adjust liquor capacity to the 300ml; the triethylamine that adds 67.0g dodecyl sulfonyl azide and 20.0g; be controlled at reaction about-10 ℃; TLC or HPLC monitoring reaction; react the methyl alcohol that adds 150ml in the reaction solution that will obtain that finishes; the concentrated hydrochloric acid that adds 120ml; temperature control is in reaction below 35 ℃, and TLC or HPLC monitoring are reacted, and reaction finishes; the reaction solution that obtains is used the 400ml saturated brine successively; the wet chemical of 400ml5%; 400ml saturated brine repetitive scrubbing; abandon water, add the anhydrous sodium sulfate dehydration drying of 100g in the organic phase, filter; filtrate decompression concentrates; add the 100g sherwood oil in the concentrated solution,, filter 35 ℃ of following stirred crystallization; filtration cakes torrefaction gets 44.5g target compound (Compound I).Mass yield 74.17%.
Compound I be known substance and the retention time of this compound in HPLC and
1H NMR spectrum is with to have article now consistent.
Embodiment 3
Under protection of inert gas; the solid of 400ml ethyl acetate and 60.0g compound III is joined in the reactor; the mixed solution (triethylamine of 64.0g dodecyl sulfonyl azide and 17.0g) that adds the nitrine-alkali that has prepared in advance; be controlled at reaction about-10 ℃; TLC or HPLC monitoring reaction; reaction finishes; the methyl alcohol of 100ml will be added in the reaction solution that obtain; the concentrated hydrochloric acid that adds 100ml; temperature control is in reaction below 35 ℃; TLC or HPLC monitoring reaction, reaction finishes the reaction solution that obtains is used the 200ml saturated brine successively; the wet chemical of 200ml5%; 200ml saturated brine repetitive scrubbing is abandoned water; the anhydrous sodium sulfate dehydration drying that adds 50g in the organic phase; filter, filtrate decompression concentrates, and adds the 120g sherwood oil in the concentrated solution; 15 ℃ of following stirred crystallization; filter, filtration cakes torrefaction gets 46.7g target compound (Compound I).Mass yield 77.83%.
Compound I be known substance and the retention time of this compound in HPLC and
1H NMR spectrum is with to have article now consistent.
Embodiment 4
Under protection of inert gas; the solid of 400ml tetrahydrofuran (THF) and 60.0g compound III is joined in the reactor; add the dimethylamine of 60.0g to carboxyl sulfonyl azide and 15.0g; be controlled at reaction about 0 ℃; TLC or HPLC monitoring reaction; reaction finishes, and will add the methyl alcohol of 200ml in the reaction solution that obtain, and adds the concentrated hydrochloric acid of 120ml; temperature control is in reaction below 35 ℃; TLC or HPLC monitoring reaction are used the 400ml saturated brine successively with the reaction solution that obtains; the wet chemical of 400ml5%; 400ml saturated brine repetitive scrubbing is abandoned water; the anhydrous sodium sulfate dehydration drying that adds 100g in the organic phase; filter, filtrate decompression concentrates, and adds the 150g sherwood oil in the concentrated solution; 35 ℃ of following stirred crystallization; filter, filtration cakes torrefaction gets 46.6g target compound (Compound I).Mass yield 77.67%.
Compound I be known substance and the retention time of this compound in HPLC and
1H NMR spectrum is with to have article now consistent.
Embodiment 5
Under protection of inert gas; the solid of 400ml tetrahydrofuran (THF) and 60.0g compound III is joined in the reactor; add the diisopropylethylamine of 60.0g to carboxyl sulfonyl azide and 15.0g; be controlled at reaction about-20 ℃; TLC or HPLC monitoring reaction; reaction finishes, and will add the methyl alcohol of 200ml in the reaction solution that obtain, and adds the concentrated hydrochloric acid of 120ml; temperature control is in reaction below 35 ℃; TLC or HPLC monitoring reaction are used the 400ml saturated brine successively with the reaction solution that obtains; the wet chemical of 400ml5%; 400ml saturated brine repetitive scrubbing is abandoned water; the anhydrous sodium sulfate dehydration drying that adds 100g in the organic phase; filter, filtrate decompression concentrates, and adds the 150g sherwood oil in the concentrated solution; 0 ℃ of following stirred crystallization; filter, filtration cakes torrefaction gets 46.4g target compound (Compound I).Mass yield 77.33%.
Compound I be known substance and the retention time of this compound in HPLC and
1H NMR spectrum is with to have article now consistent.
Embodiment 6
Under protection of inert gas; the solid of 400ml tetrahydrofuran (THF) and 60.0g compound III is joined in the reactor; the dibutylamine that adds 60.0g methylsulfonyl nitrine and 15.0g; be controlled at reaction about-20 ℃; TLC or HPLC monitoring reaction; reaction finishes, and will add the ethanol of 200ml in the reaction solution that obtain, and adds the Hydrogen bromide of 120ml; temperature control is in reaction below 35 ℃; TLC or HPLC monitoring reaction are used the 400ml saturated brine successively with the reaction solution that obtains; the wet chemical of 400ml5%; 400ml saturated brine repetitive scrubbing is abandoned water; the anhydrous sodium sulfate dehydration drying that adds 100g in the organic phase; filter, filtrate decompression concentrates, and adds the 150g sherwood oil in the concentrated solution; 0 ℃ of following stirred crystallization; filter, filtration cakes torrefaction gets 46.3g target compound (Compound I).Mass yield 77.17%.
Compound I be known substance and the retention time of this compound in HPLC and
1H NMR spectrum is with to have article now consistent.
Embodiment 7
Under protection of inert gas; the solid of 400ml ethyl acetate and 60.0g compound III is joined in the reactor; the mixed solution (triethylamine of 64.0g dodecyl sulfonyl azide and 17.0g) that adds the nitrine-alkali that has prepared in advance; be controlled at reaction about-10 ℃; TLC or HPLC monitoring reaction; reaction finishes; the methyl alcohol of 100ml will be added in the reaction solution that obtain; the concentrated hydrochloric acid that adds 100ml; temperature control is in reaction below 0 ℃; TLC or HPLC monitoring reaction, reaction finishes the reaction solution that obtains is used the 200ml saturated brine successively; the aqueous sodium carbonate of 200ml5%; 200ml saturated brine repetitive scrubbing is abandoned water; the anhydrous sodium sulfate dehydration drying that adds 50g in the organic phase; filter, filtrate decompression concentrates, and adds the 120g hexanaphthene in the concentrated solution; 15 ℃ of following stirred crystallization; filter, filtration cakes torrefaction gets 46.5g target compound (Compound I).Mass yield 77.50%.
Compound I be known substance and the retention time of this compound in HPLC and
1H NMR spectrum is with to have article now consistent.
Comparing embodiment
The solid of 400ml ethyl acetate and 60.0g compound III is joined in the reactor, add 160g methyl alcohol, the hydrochloric acid of 160g6N, be controlled at reaction about 20 ℃, TLC or HPLC monitoring reaction, reaction finishes, the saturated brine that adds 400ml in the reaction solution that obtains is washed three times, 5% salt of wormwood that adds 600ml washs three times, the saturated brine washed twice that adds 400ml, organic phase add the dehydration of 60g anhydrous sodium sulfate drying, organic phase concentrating under reduced pressure, the sherwood oil crystallization that adds 150g, intermediate 40 grams of filtration drying.The acetonitrile of this crystal and 200ml is joined in the reaction flask, add the triethylamine of 40g to dodecyl sulfonyl azide and 12.5g, temperature control reacts about 0 ℃, TLC or HPLC monitoring reaction, reaction finishes the reaction solution that obtains is used the 200ml saturated brine successively, the hydrochloric acid soln of 200m5%, 200ml saturated brine repetitive scrubbing, abandon water, the anhydrous sodium sulfate dehydration drying that adds 50g in the organic phase, filter, filtrate decompression concentrates, and adds the 120g hexanaphthene in the concentrated solution, 15 ℃ of following stirred crystallization, filter, filtration cakes torrefaction gets 39.5g target compound (Compound I).Mass yield 65.8%.
Compound I be known substance and the retention time of this compound in HPLC and
1H NMR spectrum is with to have article now consistent.
More than the description of preferred embodiment of the present invention is not limited the present invention, those skilled in the art can make various changes and distortion according to the present invention, only otherwise break away from spirit of the present invention, all should belong to the category of claims of the present invention.
Claims (10)
1. beta-methyl carbapenem antibiotic intermediates preparation may further comprise the steps:
1) formula (III) compound is reacted under the effect of diazo reagent, obtain comprising the reaction solution of formula (IV) compound;
2) with formula (IV) compound deprotection base, obtain comprising the solution of formula (I) compound,
Reaction scheme is as follows:
2. preparation method according to claim 1; wherein; step 1) is to carry out under protection of inert gas and in the presence of organic solvent and the organic bases; described organic solvent is for being selected from acetonitrile; tetrahydrofuran (THF); dimethyl formamide; diethylformamide; dioxane; ethyl acetate; methyl acetate; propyl acetate; butylacetate; methyl alcohol; ethanol; n-propyl alcohol; Virahol; acetone; and in the butanone one or more; described organic bases is for being selected from Trimethylamine 99; dimethylamine; triethylamine; diethylamine; Tributylamine; dibutylamine; trioctylamine; Di-Octyl amine; di ethamine; diisopropylethylamine; diisopropylamine; di-n-propyl amine; substituent pyridine is arranged on pyridine or the pyridine ring; the N-methyl piperidine; N-methylmorpholine; aniline; methylphenylamine; and N, one or more in the accelerine.
3. preparation method according to claim 1 and 2 wherein, in step 1), under protection of inert gas, reacts formula (III) compound or the solution that comprises formula (III) compound under the effect of diazo reagent.
4. preparation method according to claim 1 and 2, wherein, in step 1), described diazo reagent be selected from sulfonyl azide, methylsulfonyl nitrine, tolylsulfonyl nitrine, in carboxyl sulfonyl azide and the dodecyl sulfonyl azide one or more.
5. preparation method according to claim 1 wherein, after step 1), further comprises the step of acquisition formula (IV) compound crystal.
6. the alcohol that is reflected at preparation method according to claim 1, wherein, step 2) exists down and carries out, and employing acid solution or chloride compounds solution are to formula (IV) compound deprotection base.
7. preparation method according to claim 1, wherein, in step 1), temperature of reaction is controlled at-40～45 ℃.
8. preparation method according to claim 1, wherein, in step 2) in, temperature of reaction is controlled at and is no more than 60 ℃.
9. preparation method according to claim 1 wherein, further comprises the step of acquisition formula (I) compound crystal.
10. preparation method according to claim 9, wherein, washing comprises the reaction solution of formula (I) compound, abandons water, and organic phase concentrates, and adds recrystallisation solvent, and stirred crystallization is filtered, and drying obtains formula (I) compound crystal.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010232089 CN101891666B (en) | 2010-07-20 | 2010-07-20 | Preparation method of intermediate of beta methylcarbapenem antibiotics |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010232089 CN101891666B (en) | 2010-07-20 | 2010-07-20 | Preparation method of intermediate of beta methylcarbapenem antibiotics |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101891666A true CN101891666A (en) | 2010-11-24 |
| CN101891666B CN101891666B (en) | 2012-09-26 |
Family
ID=43101041
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201010232089 Active CN101891666B (en) | 2010-07-20 | 2010-07-20 | Preparation method of intermediate of beta methylcarbapenem antibiotics |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101891666B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102690282A (en) * | 2011-07-07 | 2012-09-26 | 深圳市海滨制药有限公司 | Crystal-form 1beta methylcarbapenem antibiotic intermediate and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63284176A (en) * | 1987-05-15 | 1988-11-21 | Nippon Redarii Kk | Highly stereoselective production of (1r,5r,6s)-6-((1r)-1-hydroxyethyl)-1-methylcarbapenem-3-carboxylic acid derivative |
| JPH0543575A (en) * | 1991-12-21 | 1993-02-23 | Mercian Corp | Azole derivative |
| WO1993013064A1 (en) * | 1991-12-26 | 1993-07-08 | Nippon Soda Co., Ltd. | Process for producing 4-substituted azetidinone derivative |
| CN101500992A (en) * | 2006-08-15 | 2009-08-05 | 明治制果株式会社 | Method for producing 1-methylcarbapenem production intermediate |
-
2010
- 2010-07-20 CN CN 201010232089 patent/CN101891666B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63284176A (en) * | 1987-05-15 | 1988-11-21 | Nippon Redarii Kk | Highly stereoselective production of (1r,5r,6s)-6-((1r)-1-hydroxyethyl)-1-methylcarbapenem-3-carboxylic acid derivative |
| JPH0543575A (en) * | 1991-12-21 | 1993-02-23 | Mercian Corp | Azole derivative |
| WO1993013064A1 (en) * | 1991-12-26 | 1993-07-08 | Nippon Soda Co., Ltd. | Process for producing 4-substituted azetidinone derivative |
| CN101500992A (en) * | 2006-08-15 | 2009-08-05 | 明治制果株式会社 | Method for producing 1-methylcarbapenem production intermediate |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102690282A (en) * | 2011-07-07 | 2012-09-26 | 深圳市海滨制药有限公司 | Crystal-form 1beta methylcarbapenem antibiotic intermediate and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101891666B (en) | 2012-09-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101555252B (en) | Synthetic method of antibiotic cefoxitin | |
| CN101935321A (en) | Method for synthesizing 1 beta methyl carbapenem antibiotic | |
| CN109761867B (en) | Vitamin D production by using lanolin as raw material3Is a new method for industrialization | |
| CN106866668A (en) | The method that one kettle way prepares AVM hereinafter Batan sodium | |
| CN105753867A (en) | Preparation method of improved avibactam sodium intermediate compound | |
| CN113666946B (en) | Preparation method of 2 beta-triazole methyl penicillanic acid diphenylmethyl ester, tazobactam intermediate and tazobactam | |
| CN108069998A (en) | A kind of synthetic method of penem-like pharmaceutical intermediate | |
| CN107445950B (en) | Refining method of tebipenem pivoxil side chain | |
| CN111777654B (en) | Preparation method of prednisone | |
| CN101891666B (en) | Preparation method of intermediate of beta methylcarbapenem antibiotics | |
| CN101768174B (en) | Method for preparing biapenem | |
| CN101891743A (en) | Method for synthesizing meropenem intermediate | |
| CN111560005A (en) | Preparation method of 2-thiopheneacetyl chloride | |
| CN115073458A (en) | Preparation method of avibactam sodium | |
| CN109912553A (en) | A kind of intermediate and preparation method thereof | |
| CN101560219A (en) | Synthetic method of 1 beta methyl carbapenem antibiotic midbody | |
| CN108299470B (en) | Preparation method of cefteram pivoxil | |
| CN108658872B (en) | Preparation method of avanafil intermediate | |
| CN102532140B (en) | Method for preparing meropenem trihydrate | |
| CN107674079B (en) | Synthesis method of ibrutinib | |
| CN105218562A (en) | A kind of preparation method of D (-)-Sulfocillin | |
| CN110590775A (en) | Preparation method of intermediate of Abamebactam sodium of beta-lactamase inhibitor drug | |
| CN110698469A (en) | Tebipenem pivoxil intermediate and synthetic method and application thereof | |
| CN112125957B (en) | Preparation method of caspofungin acetate | |
| CN113929684B (en) | Meropenem intermediate and preparation method thereof |
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 | ||
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20160106 Address after: Xinxiang City, Henan province 453000 East High Tech Development Zone in the neighborhood Patentee after: Xinxiang Haibin Pharmaceutical Co.,Ltd. Address before: 518081 No. 2003, Sha Mo Road, Yantian District, Guangdong, Shenzhen Patentee before: Shenzhen Haibin Pharmaceutical Co., Ltd. |