EP1178992A2 - Process for the preparation of cefpodoxime acid - Google Patents
Process for the preparation of cefpodoxime acidInfo
- Publication number
- EP1178992A2 EP1178992A2 EP00969048A EP00969048A EP1178992A2 EP 1178992 A2 EP1178992 A2 EP 1178992A2 EP 00969048 A EP00969048 A EP 00969048A EP 00969048 A EP00969048 A EP 00969048A EP 1178992 A2 EP1178992 A2 EP 1178992A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- formula
- acid
- cefpodoxime
- organic solvent
- preparation
- 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- Withdrawn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
- LTINZAODLRIQIX-FBXRGJNPSA-N cefpodoxime proxetil Chemical compound N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC)C(=O)OC(C)OC(=O)OC(C)C)C(=O)C(=N/OC)\C1=CSC(N)=N1 LTINZAODLRIQIX-FBXRGJNPSA-N 0.000 title claims abstract description 23
- 229960004797 cefpodoxime proxetil Drugs 0.000 title claims abstract description 23
- 238000000034 method Methods 0.000 title claims abstract description 22
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 27
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 27
- 238000006243 chemical reaction Methods 0.000 claims description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 239000003960 organic solvent Substances 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 6
- 150000007530 organic bases Chemical class 0.000 claims description 5
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 claims description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 claims description 4
- 150000002576 ketones Chemical class 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 230000002378 acidificating effect Effects 0.000 claims description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 230000001376 precipitating effect Effects 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 238000001556 precipitation Methods 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- BDSDFCVDQUGOFB-XNCJUZBTSA-N (6s,7s)-7-amino-3-(methoxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound S1CC(COC)=C(C(O)=O)N2C(=O)[C@H](N)[C@H]12 BDSDFCVDQUGOFB-XNCJUZBTSA-N 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 4
- 239000012258 stirred mixture Substances 0.000 description 4
- CXWZBICLYZLPRU-DGYKBKIGSA-N NC=1SC=C(N=1)/C(/C(=O)NC1[C@@H]2N(C(=C(C(S2)C)OC)C(=O)O)C1=O)=N/OC Chemical compound NC=1SC=C(N=1)/C(/C(=O)NC1[C@@H]2N(C(=C(C(S2)C)OC)C(=O)O)C1=O)=N/OC CXWZBICLYZLPRU-DGYKBKIGSA-N 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- -1 isopropyloxy carbonyl oxyethyl Chemical group 0.000 description 3
- WRTVTCFELAEIEQ-YVLHZVERSA-N o-(1,3-benzothiazol-2-yl) (2z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoethanethioate Chemical compound N=1C2=CC=CC=C2SC=1OC(=S)\C(=N/OC)C1=CSC(N)=N1 WRTVTCFELAEIEQ-YVLHZVERSA-N 0.000 description 3
- NGFHVDYYWXIYML-YVLHZVERSA-N (2Z)-2-[(2-amino-1,3-thiazol-4-yl)methoxyimino]-2-(1,3-benzothiazol-2-yl)ethanethioic S-acid Chemical compound S1C(N)=NC(CO\N=C(/C(S)=O)C=2SC3=CC=CC=C3N=2)=C1 NGFHVDYYWXIYML-YVLHZVERSA-N 0.000 description 2
- BDSDFCVDQUGOFB-SVGQVSJJSA-N (6r,7r)-7-amino-3-(methoxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound S1CC(COC)=C(C(O)=O)N2C(=O)[C@@H](N)[C@@H]12 BDSDFCVDQUGOFB-SVGQVSJJSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- KKDHWGOHWGLLPR-UHFFFAOYSA-N 1,1-bis(sulfanylidene)-3h-1,3-benzothiazole-2-thione Chemical compound C1=CC=C2S(=S)(=S)C(S)=NC2=C1 KKDHWGOHWGLLPR-UHFFFAOYSA-N 0.000 description 1
- NLARCUDOUOQRPB-UHFFFAOYSA-N 2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetic acid Chemical compound CON=C(C(O)=O)C1=CSC(N)=N1 NLARCUDOUOQRPB-UHFFFAOYSA-N 0.000 description 1
- FGEXGVRAEFBIFP-UHFFFAOYSA-N 2-[(2-amino-1,3-thiazol-4-yl)methoxyimino]ethanethioic S-acid Chemical compound C1=C(N=C(S1)N)CON=CC(=O)S FGEXGVRAEFBIFP-UHFFFAOYSA-N 0.000 description 1
- ZMWOTDSKFFYKGL-UHFFFAOYSA-N 2-methoxyiminoethanethioic S-acid Chemical compound CON=CC(S)=O ZMWOTDSKFFYKGL-UHFFFAOYSA-N 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- 206010009152 Chronic tonsillitis Diseases 0.000 description 1
- 201000007100 Pharyngitis Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 229960005090 cefpodoxime Drugs 0.000 description 1
- WYUSVOMTXWRGEK-HBWVYFAYSA-N cefpodoxime Chemical compound N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC)C(O)=O)C(=O)C(=N/OC)\C1=CSC(N)=N1 WYUSVOMTXWRGEK-HBWVYFAYSA-N 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940113088 dimethylacetamide Drugs 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 208000022760 infectious otitis media Diseases 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- BSCHIACBONPEOB-UHFFFAOYSA-N oxolane;hydrate Chemical compound O.C1CCOC1 BSCHIACBONPEOB-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229950000033 proxetil Drugs 0.000 description 1
- 239000011369 resultant mixture Substances 0.000 description 1
- 201000009890 sinusitis Diseases 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 206010044008 tonsillitis Diseases 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
Definitions
- the present invention relates to a new process for the preparation of cefpodoxime acid, an antibiotic belonging to cephalosporin class of compounds. More specifically, the present invention relates to the preparation of cefpodoxime acid of high purity and yield.
- cefpodoxime acid prepared according to the process of the present invention can be converted into its prodrug, cefpodoxime proxetil, by methods known in the art.
- Cefpodoxime proxetil is chemically an isopropyloxy carbonyl oxyethyl (proxetil) ester of cefpodoxime. It is a potent antibiotic and is of great therapeutic interest in the treatment of acute bronchitis, exacerbations, pneumonia, sinusitis, recurrence of chronic tonsillitis, pharyngitis, and acute otitis media.
- the present invention provides a process for the preparation of Cefpodoxime acid having the Formula I
- MAEM 3-methoxymethyl-7-aminocephalosporanic acid
- 7AMCA in the presence of an organic solvent and an organic base as herein described and optionally in the presence of water, washing with a water-immiscible solvent as herein described, precipitating the product by adjusting the pH to an acidic pH, isolating and drying the product having the Formula I.
- the reaction between MAEM and 7AMCA is carried out at a temperature ranging from -5°C to about ambient temperature for about 2 to 12 hours.
- the organic solvent used is selected from tetrahydrofuran, N, N-dimethylaceta- mide, N,N-dimethylformamide, chlorinated hydrocarbons, ketones or a mixture thereof.
- the reaction is carried out in tetrahydrofuran in the presence of water.
- the reaction is carried out in the presence of organic bases such as triethylamine, N-methylpiperidine, pyridine, 1 ,8-diazabicycloundecene, 4-dimeth- ylaminopyridine, or a mixture thereof.
- the water-immiscible solvent used is chlorinated hydrocarbon, aromatic hydrocarbon or ketones.
- cefpodoxime acid having the Formula I prepared according to the process of the present invention is a syn-isomer of this compound.
- the present invention provides a method by which the syn-isomer of cefpodoxime acid is obtained in high purity and good yields without the necessity for protecting the amino group of acylating agent.
- Aqueous layer was separated and washed with methylene chloride.
- the aqueous layer was acidified to pH 2.75 with aqueous hydrochloric acid and the separated product was filtered. It was washed with water and dried under reduced pressure to yield 6.65gm (76%) of Cefpodoxime acid of 95.7% purity (HPLC).
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Cephalosporin Compounds (AREA)
Abstract
A new process is described for the preparation of cefpodoxime acid, which may then be converted into cefpodoxime proxetil by methods known in the art.
Description
PROCESS FOR THE PREPARATION OF CEFPODOXIME ACID
FIELD OF THE INVENTION
The present invention relates to a new process for the preparation of cefpodoxime acid, an antibiotic belonging to cephalosporin class of compounds. More specifically, the present invention relates to the preparation of cefpodoxime acid of high purity and yield.
The cefpodoxime acid prepared according to the process of the present invention can be converted into its prodrug, cefpodoxime proxetil, by methods known in the art. Cefpodoxime proxetil is chemically an isopropyloxy carbonyl oxyethyl (proxetil) ester of cefpodoxime. It is a potent antibiotic and is of great therapeutic interest in the treatment of acute bronchitis, exacerbations, pneumonia, sinusitis, recurrence of chronic tonsillitis, pharyngitis, and acute otitis media.
BACKGROUND OF THE INVENTION
The process known for the preparation of cefpodoxime acid in the literature (Journal of Antibiotics, Vol. 40, p-370, 1987) involves conversion of 7-[2-(2- chloroacetyl amino thiazol-4-yl)-(Z)-2-(2- methoxyimino acetamido]-3-acetoxy- methyl-3-cephem-4-carboxylic acid into the corresponding 3-methoxymethyl derivative, which on deprotection at the 2-aminothiazolyl ring gives cefpodoxime acid. Esterification of the acid with iodides affords the corresponding esters. The process involves additional steps of protection and deprotection of the amino group resulting in lower yields.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide an efficient process for the preparation of cefpodoxime acid of high purity and yield, and is economical from a commercial point of view.
It is a further object of the present invention to provide a process which requires fewer steps and eliminates the use of additional protection and deprotection steps.
Accordingly, the present invention provides a process for the preparation of Cefpodoxime acid having the Formula I
FORMULA I
comprising reacting 2-[2-aminothiazol-4-yl]-2-syn-methoxyimino acetic acid-2- benzothiazolyl thioester of Formula II
FORMULA π
(referred as MAEM) with 3-methoxymethyl-7-aminocephalosporanic acid of Formula III
FORMULA m
(referred as 7AMCA), in the presence of an organic solvent and an organic base as herein described and optionally in the presence of water, washing with a water-immiscible solvent as herein described, precipitating the product by adjusting the pH to an acidic pH, isolating and drying the product having the Formula I.
Preferably the reaction between MAEM and 7AMCA is carried out at a temperature ranging from -5°C to about ambient temperature for about 2 to 12 hours.
The organic solvent used is selected from tetrahydrofuran, N, N-dimethylaceta- mide, N,N-dimethylformamide, chlorinated hydrocarbons, ketones or a mixture thereof. Preferably, the reaction is carried out in tetrahydrofuran in the presence of water. The reaction is carried out in the presence of organic bases such as triethylamine, N-methylpiperidine, pyridine, 1 ,8-diazabicycloundecene, 4-dimeth- ylaminopyridine, or a mixture thereof.
The water-immiscible solvent used is chlorinated hydrocarbon, aromatic hydrocarbon or ketones.
The cefpodoxime acid having the Formula I prepared according to the process of the present invention is a syn-isomer of this compound.
The present invention provides a method by which the syn-isomer of cefpodoxime acid is obtained in high purity and good yields without the necessity for protecting the amino group of acylating agent.
The present invention is further illustrated by the following examples :
DETAILED DESCRIPTION OF THE INVENTION
EXAMPLE 1
Preparation of 7-[(Z)-2-(2-Amino-4-thiazolyl)-2-(methoxyimino)acetamido]-3- methoxy-methyl-3-cephem-4-carboxylic acid.
To a stirred mixture of 2-benzothiazolyl(Z)-2-(aminothiazol-4-yl) methoxyimino- thioacetate (7.89g)and 7-amino-3-methoxymethyl-3-cephem-4-carboxyIic acid (5.0g) in tetrahydrofuran and water was added triethylamine (2.58g) in tetra- hydrofuran-water at 2-3-C. The reaction mixture was stirred at 2-3QC for 4 hours. After completion of the reaction, it was washed with methylene chloride. The aqueous layer was separated and its pH was adjusted to 2.75 with aqueous hydrochloric acid. The product thus separated was filtered, washed with water and isopropanol. The product was dried under reduced pressure to yield 6.65 gm (76%) of Cefpodoxime acid of 95.56% purity (HPLC).
EXAMPLE 2
Preparation of 7-[(Z)-2-(2-Amino-4-thiazolyl)-(2-methoxyimino)acetamido]-3- methoxy-methyl-3-cephem-4-carboxylic acid.
To a stirred mixture of 2-benzothiazolyl(Z)-2-(aminothiazol-4-yl)methoxyimino- thioacetate (8.6g) and 7-amino-3-methoxymethyl-3-cephem-4-carboxylic acid (5.0g) in methylene chloride (75ml) was added triethylamine (7.24g) at 2-39C. The reaction mixture was stirred at 2-3QC for 3 hr. and water was added. The aqueous layer was separated and washed with methylene chloride. It was acidi-
tied to pH 2.70 with aqueous hydrochloric acid. The product thus separated was filtered, washed and dried under reduced pressure to yield 6.2gm (70.8%) of Cefpodoxime acid of 94.30% purity (HPLC).
EXAMPLE 3
Preparation of 7-[(Z)-2-(2-Amino-4-thiazolyl)-2-(methoxyimino)acetamido]-3- methoxy-methyl-3-cephem-4-carboxylic acid.
To a stirred mixture of 2-benzothiazolyl(Z)-2-(aminothiazolyl-4-yl)methoxyimino- thioacetate (7.89g) and 7-amino-3-methoxymethyl-3-cephem-4-carboxylic acid in acetone and water, was added triethylamine (2.06g). The reaction mixture was stirred at 5-7sC for 6 hrs. After completion of the reaction, it was washed with methylene chloride and aqueous layer was separated. The aqueous layer was acidified to pH 2.75 with aqueous hydrochloric acid. The product thus separated was filtered and washed with water and acetone. It was dried under reduced pressure at 45QC to afford 5.8gm (66%) of Cefpodoxime acid of 91.8% purity (HPLC).
EXAMPLE 4
Preparation of 7-[(Z)-2-(2-Amino-4-thiazolyl)-2-(methoxyimino)acetamido]-3- methoxy-methyl-3-cephem-4-carboxylic acid.
To a mixture of N,N-dimethylformamide and water, were added at 0-5QC, 7- amino-3-methoxymethyl-3-cephem-4-carboxylic acid (5.0g), 2-benzothiazolyl(Z)-
(2-aminothiazol-4-yl)methoxyiminothioacetate (8.6g) and triethylamine (2.89g).
The resulting mixture was stirred at 10-15SC for 6 hrs. After completion of the
reaction, the pH of the reaction was adjusted to 6.5 and stirred with methylene chloride (50ml). The aqueous layer was separated and acidified to pH 2.75 with aqueous hydrochloric acid. The product thus separated was filtered, washed with water and isopropanol, and dried under reduced pressure at 40QC to yield 4.9gm (56%) of Cefpodoxime acid of 94.92% purity (HPLC).
EXAMPLE 5
Preparation of 7-[(Z)-2-(2-Amino-4-thiazolyl)-2-(methoxyimino)acetamido]-3- methoxy-methyI-3-cephem-4-carboxylic acid.
To a stirred mixture of 7-amino-3-methoxymethyl-3-cephem-4-carboxylic acid (5.0g) in water (75ml) was added triethylamine (2.0 gm) at 2-5sC. To this was added a solution of 2-benzothiazolyl-(Z)-2-(aminothiazol-4-yl)methoxyiminothio- acetate (7.88gm) in dimethylacetamide at 2-5-C. The resultant mixture was stirred at 20-25sC for 12 hrs. After completion of the reaction, the reaction mixture was washed with methylene chloride. The aqueous layer was separated and pH was adjusted to 2.7 with aqueous hydrochloric acid. The solid thus separated was filtered and washed with cold water. The product was dried under reduced pressure at 40-45QC to yield 5.5gm (62%) of Cefpodoxime acid of 93.38% purity (HPLC).
EXAMPLE 6
Preparation of 7-[(Z)-2-(2-Amino-4-thiazolyl)-2-(methoxyimino)acetamido]-3- methoxy-methyl-3-cephem-4-carboxylic acid] (Via in situ-generated MAEM):
A slurry containing triphenylphosphine (8.22g) and mercaptobenzothiazole disulphide (10.04g) in methylene chloride was stirred at 28-30QC for 1 hr. 2- (Aminothiazole-4-yl)- methoxyimino acetic acid (4.84g) and triethylamine (2.61 g) were added at 09C and stirred at 0-25C for 1 hr. 7-Amino-3-methoxymethyl-3- cephem-4-carboxylic acid (5.0g) and triethylamine (3.2g) were added and the resulting reaction mixture and further stirred for 2 hrs. After completion of the reaction, water was added and stirred for 10 min. Aqueous layer was separated and washed with methylene chloride. The aqueous layer was acidified to pH 2.75 with aqueous hydrochloric acid and the separated product was filtered. It was washed with water and dried under reduced pressure to yield 6.65gm (76%) of Cefpodoxime acid of 95.7% purity (HPLC).
Claims
LAIM :
A process for the preparation of cefpodoxime acid having the Formula I
FORMULA I
which comprises reacting 2-[2-aminothiazol-4yl]-2-syn-methoxyiminoacetic acid -2-benzothiazolyl thioester of Formula II,
FORMULA π
with 3-methoxymethyl-7-aminocephalosporanic acid of Formula III,
FORMULA ffl in the presence of an organic solvent and an organic base, precipitating the product by adjusting the pH to an acidic pH, isolating and drying the product having the Formula I.
2. The process of claim 1 , wherein after the reaction in the presence of an organic solvent and an organic base, before precipitation, the product is washed with a water-immiscible solvent.
3. The process of claim 1 , wherein cefpodoxime acid having the Formula I is a syn-isomer.
4. The process of claim 1 , wherein the organic solvent used is tetrahydrofuran, N,N-dimethylacetamide, N,N-dimethylformamide, chlorinated hydrocarbons, ketones or mixtures thereof.
5. The process of claim 4, wherein the organic solvent is methylene chloride.
6. The process of claim 1 , wherein the organic base is triethylamine, pyridine, N-methylpiperidine, 1 , 8-diazabicycloundecene, 4- dimethylaminopyridine or mixtures thereof.
7. The process of claim 1 , wherein the said reaction is carried out at a temperature in the range of -5QC to about ambient temperature for about 2 to 12 hours.
8. The process of claim 2, wherein the water-immiscible organic solvent is chlorinated hydrocarbon, aromatic hydrocarbon or ketones.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US30701099A | 1999-05-07 | 1999-05-07 | |
| US307010 | 1999-05-07 | ||
| PCT/IB2000/000585 WO2000068234A2 (en) | 1999-05-07 | 2000-05-05 | Process for the preparation of cefpodoxime acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP1178992A2 true EP1178992A2 (en) | 2002-02-13 |
Family
ID=23187851
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP00969048A Withdrawn EP1178992A2 (en) | 1999-05-07 | 2000-05-05 | Process for the preparation of cefpodoxime acid |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP1178992A2 (en) |
| AU (1) | AU7224300A (en) |
| HK (1) | HK1044761A1 (en) |
| WO (1) | WO2000068234A2 (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004037833A1 (en) * | 2002-10-24 | 2004-05-06 | Orchid Chemicals & Pharmaceuticals Ltd | Process for the preparation of cephalosporin antibiotics |
| WO2011077217A1 (en) * | 2009-12-21 | 2011-06-30 | Nectar Lifesciences Ltd. | An improved process for the preparation of cefpodoxime acid |
| CN106046024B (en) * | 2016-06-30 | 2019-01-15 | 齐鲁动物保健品有限公司 | A kind of preparation method of Cefpodoxime Proxetil |
| CN111320514A (en) * | 2020-04-03 | 2020-06-23 | 南京昊绿生物科技有限公司 | Synthesis method of cefpodoxime D3 |
| CN116003438B (en) * | 2022-12-28 | 2025-09-05 | 广药白云山化学制药(珠海)有限公司 | A preparation method of cephalosporin intermediate |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0037380A2 (en) | 1980-03-28 | 1981-10-07 | BIOCHEMIE Gesellschaft m.b.H. | New process for the production of cephalosporin antibiotics, and novel intermediates used in such process and their production |
| WO1998031685A1 (en) | 1997-01-16 | 1998-07-23 | Biochemie Gesellschaft Mbh | Purification process |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2476087A1 (en) * | 1980-02-18 | 1981-08-21 | Roussel Uclaf | NOVEL OXIMES DERIVED FROM 3-ALKYLOXY OR 3-ALKYL-THIOMETHYL 7-AMINO THIAZOLYL ACETAMIDO CEPHALOSPORANIC ACID, PROCESS FOR PREPARING THEM AND THEIR APPLICATION AS MEDICAMENTS |
| JPS60260584A (en) * | 1985-05-14 | 1985-12-23 | Sankyo Co Ltd | Cephalosporin derivative and its preparation |
| JPS60260583A (en) * | 1985-05-14 | 1985-12-23 | Sankyo Co Ltd | Preparation of cephalosporin derivative |
| EP0531875B1 (en) * | 1991-09-07 | 2004-03-24 | Aventis Pharma Deutschland GmbH | Diastereomer of the 3-cephem-4-carboxylic acid-1-(-isopropoxycarbonyloxy)ethylester and process for its preparation |
-
2000
- 2000-05-05 HK HK02105883.7A patent/HK1044761A1/en unknown
- 2000-05-05 WO PCT/IB2000/000585 patent/WO2000068234A2/en not_active Ceased
- 2000-05-05 EP EP00969048A patent/EP1178992A2/en not_active Withdrawn
- 2000-05-05 AU AU72243/00A patent/AU7224300A/en not_active Abandoned
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0037380A2 (en) | 1980-03-28 | 1981-10-07 | BIOCHEMIE Gesellschaft m.b.H. | New process for the production of cephalosporin antibiotics, and novel intermediates used in such process and their production |
| WO1998031685A1 (en) | 1997-01-16 | 1998-07-23 | Biochemie Gesellschaft Mbh | Purification process |
Non-Patent Citations (1)
| Title |
|---|
| See also references of WO0068234A3 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2000068234A2 (en) | 2000-11-16 |
| WO2000068234A3 (en) | 2001-02-08 |
| HK1044761A1 (en) | 2002-11-01 |
| AU7224300A (en) | 2000-11-21 |
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