CN114573603A - Process for synthesizing pimecrcillin in one pot - Google Patents
Process for synthesizing pimecrcillin in one pot Download PDFInfo
- Publication number
- CN114573603A CN114573603A CN202210211283.9A CN202210211283A CN114573603A CN 114573603 A CN114573603 A CN 114573603A CN 202210211283 A CN202210211283 A CN 202210211283A CN 114573603 A CN114573603 A CN 114573603A
- Authority
- CN
- China
- Prior art keywords
- pivampicillin
- solvent
- reaction
- preparing
- apa
- 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.)
- Withdrawn
Links
- 238000000034 method Methods 0.000 title claims abstract description 16
- 238000005580 one pot reaction Methods 0.000 title abstract description 5
- 230000002194 synthesizing effect Effects 0.000 title description 4
- ZEMIJUDPLILVNQ-ZXFNITATSA-N pivampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)[C@H](C(S3)(C)C)C(=O)OCOC(=O)C(C)(C)C)=CC=CC=C1 ZEMIJUDPLILVNQ-ZXFNITATSA-N 0.000 claims abstract description 21
- 229960003342 pivampicillin Drugs 0.000 claims abstract description 21
- NGHVIOIJCVXTGV-ALEPSDHESA-N 6-aminopenicillanic acid Chemical compound [O-]C(=O)[C@H]1C(C)(C)S[C@@H]2[C@H]([NH3+])C(=O)N21 NGHVIOIJCVXTGV-ALEPSDHESA-N 0.000 claims abstract description 12
- NGHVIOIJCVXTGV-UHFFFAOYSA-N 6beta-amino-penicillanic acid Natural products OC(=O)C1C(C)(C)SC2C(N)C(=O)N21 NGHVIOIJCVXTGV-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000004519 manufacturing process Methods 0.000 claims abstract description 6
- 238000006243 chemical reaction Methods 0.000 claims description 24
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 12
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical group [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 12
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 9
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims description 9
- 239000000047 product Substances 0.000 claims description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 7
- GGRHYQCXXYLUTL-UHFFFAOYSA-N chloromethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCCl GGRHYQCXXYLUTL-UHFFFAOYSA-N 0.000 claims description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 6
- 239000003513 alkali Substances 0.000 claims description 6
- 239000003054 catalyst Substances 0.000 claims description 6
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- AIPVTTKYSPOWFO-UHFFFAOYSA-N azepane-1-carbaldehyde Chemical compound O=CN1CCCCCC1 AIPVTTKYSPOWFO-UHFFFAOYSA-N 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 5
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 claims description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical group [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- 239000012043 crude product Substances 0.000 claims description 4
- 238000001914 filtration Methods 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 claims description 4
- 235000009518 sodium iodide Nutrition 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- YOYAIZYFCNQIRF-UHFFFAOYSA-N 2,6-dichlorobenzonitrile Chemical compound ClC1=CC=CC(Cl)=C1C#N YOYAIZYFCNQIRF-UHFFFAOYSA-N 0.000 claims description 2
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 2
- 238000001816 cooling Methods 0.000 claims description 2
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Chemical group CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 claims description 2
- 229940011051 isopropyl acetate Drugs 0.000 claims description 2
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical group CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 238000004321 preservation Methods 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- NNGAQKAUYDTUQR-UHFFFAOYSA-N cyclohexanimine Chemical compound N=C1CCCCC1 NNGAQKAUYDTUQR-UHFFFAOYSA-N 0.000 claims 1
- 230000035484 reaction time Effects 0.000 claims 1
- 229930182555 Penicillin Natural products 0.000 abstract description 7
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 abstract description 6
- 229940049954 penicillin Drugs 0.000 abstract description 6
- 230000015572 biosynthetic process Effects 0.000 abstract description 5
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract description 4
- 230000029936 alkylation Effects 0.000 abstract description 3
- 238000005804 alkylation reaction Methods 0.000 abstract description 3
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract description 2
- 229910052757 nitrogen Inorganic materials 0.000 abstract description 2
- 229910052760 oxygen Inorganic materials 0.000 abstract description 2
- 239000001301 oxygen Substances 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 230000001580 bacterial effect Effects 0.000 abstract 1
- 210000002421 cell wall Anatomy 0.000 abstract 1
- 230000002452 interceptive effect Effects 0.000 abstract 1
- 239000012065 filter cake Substances 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 239000012265 solid product Substances 0.000 description 2
- 238000000967 suction filtration Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000588914 Enterobacter Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 241000588748 Klebsiella Species 0.000 description 1
- 208000037386 Typhoid Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- NPGNOVNWUSPMDP-UTEPHESZSA-N chembl1650818 Chemical compound N(/[C@H]1[C@@H]2N(C1=O)[C@H](C(S2)(C)C)C(=O)OCOC(=O)C(C)(C)C)=C\N1CCCCCC1 NPGNOVNWUSPMDP-UTEPHESZSA-N 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000002960 penicillins Chemical class 0.000 description 1
- NPGNOVNWUSPMDP-HLLBOEOZSA-N pivmecillinam Chemical compound N([C@H]1[C@@H]2N(C1=O)[C@H](C(S2)(C)C)C(=O)OCOC(=O)C(C)(C)C)=CN1CCCCCC1 NPGNOVNWUSPMDP-HLLBOEOZSA-N 0.000 description 1
- 229960004212 pivmecillinam Drugs 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 201000008297 typhoid fever Diseases 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D499/21—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring with a nitrogen atom directly attached in position 6 and a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2
- C07D499/28—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring with a nitrogen atom directly attached in position 6 and a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2 with modified 2-carboxyl group
- C07D499/32—Esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D499/04—Preparation
- C07D499/08—Modification of a carboxyl radical directly attached in position 2, e.g. esterification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D499/04—Preparation
- C07D499/10—Modification of an amino radical directly attached in position 6
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a simple method for preparing pimecrcillin, which is an oral broad-spectrum semi-synthetic penicillin having an antibacterial effect by interfering the biosynthesis of bacterial cell walls. The method adopts a one-pot process route, takes 6-APA as a starting raw material, and synthesizes the pivampicillin by the methods of oxygen alkylation and nitrogen imidization. The invention has the advantages of simple synthesis process, low production cost, few steps, high total yield and little pollution, and is suitable for industrial mass production.
Description
Technical Field
The invention relates to the technical field of medicinal chemistry and medicinal synthesis, in particular to an improved pivampicillin synthesis process.
Technical Field
Pimeicillin is an oral broad-spectrum antibiotic, is semi-synthetic penicillin, and can be used for treating simple or compound urinary tract infection caused by sensitive bacteria such as Escherichia coli, Klebsiella, Enterobacter, etc., and can also be used for treating typhoid fever.
Pimeicillin, the name of English Pivmecillinam, CAS number 32886-97-8, and its molecular formula C21H33N3O5S, molecular weight 439.57, white solid in appearance. The chemical formula is as follows:
penicillin is one of important antibiotics and has a good antibacterial effect, but is not acid-resistant, enzyme-resistant, has a narrow antibacterial spectrum and is easy to cause allergy, and in order to solve the problems, people begin to research and successfully obtain a plurality of semi-synthetic penicillins, and a synthetic method mainly structurally modifies 6-aminopenicillanic acid (6-APA) obtained from penicillin fermentation liquor. More than 40 semi-synthetic penicillin products are clinically applied at present, and one of the semi-synthetic penicillin products is enzyme-resistant pivampicillin. The synthesis reaction equation is as follows:
the 6-APA is prepared by obtaining an alkylation product with chloromethyl pivalate and then reacting with N-formyl cyclohexylimine, and has less reaction steps, low temperature requirement, high toxic reagent requirement and production cost increase.
Disclosure of Invention
The invention aims to provide a method for synthesizing pivampicillin in one pot, which is prepared by taking 6-APA as a starting raw material through oxygen alkylation and nitrogen imidization in one pot. The aim of the invention is achieved by the following technical measures:
adding 6-APA, a catalyst, an alkali reagent, a solvent A and chloromethyl pivalate into a reaction kettle, and reacting for 20-24 hours at the temperature of 20-30 ℃; adding N-formyl hexamethylene imine dimethyl sulfate into the reaction kettle after the reaction is finished, heating to 50-60 ℃, and carrying out heat preservation reaction for 5-7 hours; after the reaction is finished, adding a certain amount of water into the reaction kettle, fully stirring, and filtering to obtain a white solid which is a crude product of pivampicillin; and adding the crude product into the solvent B, fully stirring, heating to be completely dissolved, then cooling and crystallizing, filtering, and drying at 60-70 ℃ to obtain the product.
Wherein the reaction equation of the pimecrillin is as follows:
further, the mass ratio of the 6-APA, the catalyst, the alkali reagent, the solvent A, the chloromethyl pivalate, the N-formyl hexamethylene imine dimethyl sulfate, the water and the solvent B is 1 (0.05-0.08): 1.4-2.5): 3-5): 0.7-1): 1.2-1.5): 3-5): 5-7, preferably 1:0.06:1.8:4:0.8:1.3:4: 6;
further, the catalyst is sodium iodide, potassium iodide, preferably sodium iodide;
further, the alkali reagent is sodium carbonate, potassium carbonate, triethylamine, diisopropylethylamine, DBU, DBN, preferably triethylamine;
further, the solvent A is dichloromethane, 1, 2-dichloroethane, chloroform, carbon tetrachloride, acetonitrile, propionitrile, acetone, butanone, methyltetrahydrofuran, 1, 4-dioxane, DMF, N-methylpyrrolidone, preferably DMF;
further, the solvent B is acetonitrile, propionitrile, acetone, butanone, ethyl acetate, isopropyl acetate, preferably acetone.
The method for preparing pivampicillin has the advantages of simple synthesis process, low production cost, few steps, high total yield, little pollution and suitability for industrial mass production.
Drawings
FIG. 1 is an infrared spectrum (IR) of the pivampicillin product synthesized in example 1
FIG. 2 is a Mass Spectrum (MS) of the pivampicillin product synthesized in example 1
FIG. 3 is the NMR spectrum of pivampicillin product synthesized in example 1: (1HNMR)
Detailed Description
The following examples will enable one skilled in the art to more fully understand the present invention, but are not intended to limit the invention in any way.
Example 1
The method for synthesizing the pivampicillin specifically comprises the following operations:
adding 100.0g of 6-APA, 6g of sodium iodide, 180g of triethylamine, 400g of DMF and 80g of chloromethyl pivalate into a reaction bottle, and controlling the temperature to be 20-30 ℃ to react for 22 hours; after the reaction is finished, adding 130g N-formyl hexamethylene imine dimethyl sulfate, controlling the temperature to be 50-60 ℃, and continuing the reaction for 6 hours; after the reaction, 400g of water is added into the reaction solution, solid is separated out, and a filter cake is obtained by suction filtration. Adding 600g of acetone into the filter cake for recrystallization, and drying the crystals at 60-70 ℃ to obtain 183.5g of a white solid product, namely pivampicillin, wherein the yield is 86.6%.
Example 2
Preparation of pivampicillin:
adding 100.0g of 6-APA, 7g of potassium iodide, 210g of diisopropylethylamine, 500g of DMF and 85g of chloromethyl pivalate into a reaction bottle, and controlling the temperature to be 20-30 ℃ to react for 21 hours; after the reaction is finished, adding 135g N-formyl hexamethylene imine dimethyl sulfate, controlling the temperature to be 50-60 ℃ and continuing the reaction for 6 hours; after the reaction, 500g of water is added into the reaction solution, solid is separated out, and a filter cake is obtained by suction filtration. Adding 600g of acetone into the filter cake for recrystallization, and drying the crystals at 60-70 ℃ to obtain 168.5g of a white solid product, namely pivampicillin, with the yield of 79.5 percent.
While the invention has been described in detail by way of the general description and the specific examples, it will be apparent to those skilled in the art that various modifications and improvements can be made without departing from the spirit of the invention.
Claims (8)
1. The preparation method of the pivampicillin is characterized in that 6-aminopenicillanic acid (6-APA), a catalyst, an alkali reagent, a solvent A and chloromethyl pivalate are added into a reaction kettle to react for a certain time at the temperature of 20-30 ℃; after the reaction is finished, adding N-formyl hexamethylene imine dimethyl sulfate into the reaction kettle, heating to 50-60 ℃, and carrying out heat preservation reaction for a certain time; after the reaction is finished, adding a certain amount of water into the reaction kettle, fully stirring, and filtering to obtain a white solid which is a crude product of pivampicillin; and adding the crude product into the solvent B, fully stirring, heating to be completely dissolved, then cooling and crystallizing, and filtering and drying to obtain the product pivampicillin.
2. The method for preparing pivampicillin as claimed in claim 1, wherein the mass ratio of 6-APA, catalyst, alkali agent, solvent A, chloromethyl pivalate, N-formyl cyclohexylimine dimethyl sulfate, water and solvent B is 1 (0.05-0.08), (1.4-2.5), (3-5), (0.7-1), (1.2-1.5), (3-5), (5-7).
3. The method for preparing pivampicillin as claimed in claim 1, wherein the catalyst is sodium iodide or potassium iodide.
4. The process for producing pivampicillin as claimed in claim 1, wherein said alkali agent is sodium carbonate, potassium carbonate, triethylamine, diisopropylethylamine, DBU or DBN, etc.
5. The process for producing pivampicillin as claimed in claim 1, wherein said solvent A is dichloromethane, 1, 2-dichloroethane, chloroform, carbon tetrachloride, acetonitrile, propionitrile, acetone, methyl ethyl ketone, methyl tetrahydrofuran, 1, 4-dioxane, DMF or N-methylpyrrolidone, etc.
6. The process for preparing pimecrocillin as claimed in claim 1, wherein the solvent B is acetonitrile, propionitrile, acetone, butanone, ethyl acetate, isopropyl acetate or the like.
7. The method for preparing pimecrocillin as claimed in claim 1, wherein the reaction time is 20 to 24 hours and 5 to 7 hours, respectively.
8. The pivampicillin preparation method as claimed in claim 1, wherein the drying temperature is 60-70 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210211283.9A CN114573603A (en) | 2022-03-07 | 2022-03-07 | Process for synthesizing pimecrcillin in one pot |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210211283.9A CN114573603A (en) | 2022-03-07 | 2022-03-07 | Process for synthesizing pimecrcillin in one pot |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN114573603A true CN114573603A (en) | 2022-06-03 |
Family
ID=81779164
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210211283.9A Withdrawn CN114573603A (en) | 2022-03-07 | 2022-03-07 | Process for synthesizing pimecrcillin in one pot |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114573603A (en) |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1293590A (en) * | 1969-11-11 | 1972-10-18 | Leo Pharm Prod Ltd | New penicillanic acid derivatives |
| PL84031B1 (en) * | 1973-11-10 | 1976-02-28 | ||
| GB1482388A (en) * | 1975-01-06 | 1977-08-10 | Inst Organicheskogo Sinteza Ak | Method of producing 6-beta-amidinopenicillanic acid derivatives |
| IT7921862A0 (en) * | 1979-04-13 | 1979-04-13 | Archifar Lab Chim Farm | METHOD FOR THE PRODUCTION OF ESTERS OF DERIVATIVES OF 6-B-AMIDINO-PENICILLANIC ACID. |
| US4278792A (en) * | 1979-04-12 | 1981-07-14 | Archifar Laboratori Chimice Farmacologici S.P.A. | Method of producing derivatives of 6-β-amidinopenicillanic acid |
| CN101735244A (en) * | 2008-11-05 | 2010-06-16 | 鲁南制药集团股份有限公司 | Method for preparing broad-spectrum penicillin antibiotic ticarcillin sodium |
| US20200230114A1 (en) * | 2019-01-22 | 2020-07-23 | Board Of Regents Of The Nevada System Of Higher Education On Behalf Of Nevada | The use of lipophilic beta-lactam antibiotics and carboxylate esters for the treatment of bacterial infections within citrus and other plant species |
-
2022
- 2022-03-07 CN CN202210211283.9A patent/CN114573603A/en not_active Withdrawn
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1293590A (en) * | 1969-11-11 | 1972-10-18 | Leo Pharm Prod Ltd | New penicillanic acid derivatives |
| PL84031B1 (en) * | 1973-11-10 | 1976-02-28 | ||
| GB1482388A (en) * | 1975-01-06 | 1977-08-10 | Inst Organicheskogo Sinteza Ak | Method of producing 6-beta-amidinopenicillanic acid derivatives |
| US4278792A (en) * | 1979-04-12 | 1981-07-14 | Archifar Laboratori Chimice Farmacologici S.P.A. | Method of producing derivatives of 6-β-amidinopenicillanic acid |
| IT7921862A0 (en) * | 1979-04-13 | 1979-04-13 | Archifar Lab Chim Farm | METHOD FOR THE PRODUCTION OF ESTERS OF DERIVATIVES OF 6-B-AMIDINO-PENICILLANIC ACID. |
| CN101735244A (en) * | 2008-11-05 | 2010-06-16 | 鲁南制药集团股份有限公司 | Method for preparing broad-spectrum penicillin antibiotic ticarcillin sodium |
| US20200230114A1 (en) * | 2019-01-22 | 2020-07-23 | Board Of Regents Of The Nevada System Of Higher Education On Behalf Of Nevada | The use of lipophilic beta-lactam antibiotics and carboxylate esters for the treatment of bacterial infections within citrus and other plant species |
Non-Patent Citations (1)
| Title |
|---|
| EDUARDO L. SETTI等: "Synthesis of (pivaloyloxy)methyl 6α-fluoropenicillanate", 《J. CHEM. SOC., PERKIN TRANS. 1》, no. 8, 31 December 1988 (1988-12-31), pages 2059 - 2060 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101613361B (en) | Method for preparing cefoxitin sodium | |
| CN104193765B (en) | A kind of synthetic method of cefixime | |
| CN101704827B (en) | Synthesis method of cefathiamidine compound | |
| CN107973796B (en) | Preparation method of tadalafil isomer | |
| CN114573603A (en) | Process for synthesizing pimecrcillin in one pot | |
| CN102127068A (en) | Method for synthesizing aztreonam compound | |
| CN110003238A (en) | A kind of preparation method of cefotiam | |
| CN110684039B (en) | Preparation method of cefoxitin lactone | |
| CN108840877B (en) | Preparation method of oxygen cephalosporin intermediate | |
| CN108299469B (en) | Preparation method of cefotiam hydrochloride | |
| KR20110088755A (en) | Method for preparing intermediates of imipenem | |
| CN105385746A (en) | Method for synthesizing cefoxitin acid | |
| CN112694487B (en) | Preparation method of cefprozil | |
| CN114105903B (en) | Preparation method of high-purity desmethyl aminothiaoxime | |
| CN113185538B (en) | Preparation method of cefpodoxime acid | |
| US3868364A (en) | Improved process for producing penicillin compound | |
| CN102532125A (en) | Synthesis method for aztreonam compound | |
| CN113801141B (en) | Preparation method of cefetamet pivoxil hydrochloride | |
| CN112759556B (en) | Synthetic method for preparing 5-mercapto-1, 2, 3-triazole sodium salt by one-pot method | |
| CN109956958B (en) | Synthesis method of 7-amino-3-methoxymethyl-3-cephem-4-carboxylic acid | |
| CN110241167B (en) | Method for preparing cefamandole nafate derivative by enzyme method | |
| KR0131050B1 (en) | Novel amine compounds and process preparing thereof | |
| CN115368283A (en) | Preparation method of cis-3-fluoro-4-hydroxypyrrolidine with chiral structure or achiral structure and derivatives thereof | |
| CN118084740A (en) | Preparation method of acetoguanidine | |
| CN111892612A (en) | Intermediate isomeride for preparing cefuroxime from penicillin sylvite and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20220603 |
|
| WW01 | Invention patent application withdrawn after publication |