GB1572912A - Clavulanic acid esters - Google Patents
Clavulanic acid esters Download PDFInfo
- Publication number
- GB1572912A GB1572912A GB2031/77A GB203177A GB1572912A GB 1572912 A GB1572912 A GB 1572912A GB 2031/77 A GB2031/77 A GB 2031/77A GB 203177 A GB203177 A GB 203177A GB 1572912 A GB1572912 A GB 1572912A
- Authority
- GB
- United Kingdom
- Prior art keywords
- compound
- group
- ethyl acetate
- eluted
- silica gel
- 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.)
- Expired
Links
- HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical class OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 title claims description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 57
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 32
- 150000001875 compounds Chemical class 0.000 claims description 21
- HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 claims description 19
- -1 p-chlorophenoxymethyl ester Chemical class 0.000 claims description 16
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 claims description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 13
- 229960003324 clavulanic acid Drugs 0.000 claims description 13
- 239000000741 silica gel Substances 0.000 claims description 13
- 229910002027 silica gel Inorganic materials 0.000 claims description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 11
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 238000006243 chemical reaction Methods 0.000 claims description 7
- 229940090805 clavulanate Drugs 0.000 claims description 6
- 238000004440 column chromatography Methods 0.000 claims description 6
- 238000001704 evaporation Methods 0.000 claims description 6
- 230000008020 evaporation Effects 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 239000000047 product Substances 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 4
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 150000001993 dienes Chemical class 0.000 claims description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methylcyclopentane Chemical compound CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 239000011541 reaction mixture Substances 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 239000006188 syrup Substances 0.000 claims description 4
- 235000020357 syrup Nutrition 0.000 claims description 4
- 238000004809 thin layer chromatography Methods 0.000 claims description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 239000003153 chemical reaction reagent Substances 0.000 claims description 3
- 239000000460 chlorine Substances 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 238000001816 cooling Methods 0.000 claims description 3
- 239000003480 eluent Substances 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 3
- ZZANIAXZVKHZNH-UHFFFAOYSA-N 1-(chloromethoxymethyl)-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(COCCl)C=C1 ZZANIAXZVKHZNH-UHFFFAOYSA-N 0.000 claims description 2
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
- GLYOPNLBKCBTMI-UHFFFAOYSA-N [2-chloro-2-(1-chloro-2-phenylethoxy)ethyl]benzene Chemical compound C=1C=CC=CC=1CC(Cl)OC(Cl)CC1=CC=CC=C1 GLYOPNLBKCBTMI-UHFFFAOYSA-N 0.000 claims description 2
- 238000004458 analytical method Methods 0.000 claims description 2
- 239000007795 chemical reaction product Substances 0.000 claims description 2
- 238000004587 chromatography analysis Methods 0.000 claims description 2
- 239000002024 ethyl acetate extract Substances 0.000 claims description 2
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 2
- 239000012535 impurity Substances 0.000 claims description 2
- 238000002329 infrared spectrum Methods 0.000 claims description 2
- 239000000463 material Substances 0.000 claims description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 2
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- 230000005855 radiation Effects 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 claims description 2
- 235000011152 sodium sulphate Nutrition 0.000 claims description 2
- 239000007921 spray Substances 0.000 claims description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 2
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 claims 1
- 229940093499 ethyl acetate Drugs 0.000 description 11
- 235000019439 ethyl acetate Nutrition 0.000 description 11
- 150000002148 esters Chemical class 0.000 description 9
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 7
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 description 1
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- JMRXTGCDVQLAFM-JSYANWSFSA-M lithium;(2r,3z,5r)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylate Chemical compound [Li+].[O-]C(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 JMRXTGCDVQLAFM-JSYANWSFSA-M 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D503/00—Heterocyclic compounds containing 4-oxa-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. oxapenicillins, clavulanic acid derivatives; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Priority Applications (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB2031/77A GB1572912A (en) | 1977-01-19 | 1977-01-19 | Clavulanic acid esters |
| BE184209A BE862764A (fr) | 1977-01-19 | 1978-01-09 | Esters de l'acide clavulanique |
| FR7800673A FR2378035A1 (fr) | 1977-01-19 | 1978-01-11 | Esters de l'acide clavulanique |
| JP323178A JPS5390289A (en) | 1977-01-19 | 1978-01-14 | Curabalanic esters and process for preparing same |
| NL7800604A NL7800604A (nl) | 1977-01-19 | 1978-01-18 | Esters van clavulanzuur en werkwijze ter be- reiding van deze esters. |
| DE19782802049 DE2802049A1 (de) | 1977-01-19 | 1978-01-18 | Clavulansaeure-ester und verfahren zu ihrer herstellung |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB2031/77A GB1572912A (en) | 1977-01-19 | 1977-01-19 | Clavulanic acid esters |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB1572912A true GB1572912A (en) | 1980-08-06 |
Family
ID=9732402
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB2031/77A Expired GB1572912A (en) | 1977-01-19 | 1977-01-19 | Clavulanic acid esters |
Country Status (6)
| Country | Link |
|---|---|
| JP (1) | JPS5390289A (en, 2012) |
| BE (1) | BE862764A (en, 2012) |
| DE (1) | DE2802049A1 (en, 2012) |
| FR (1) | FR2378035A1 (en, 2012) |
| GB (1) | GB1572912A (en, 2012) |
| NL (1) | NL7800604A (en, 2012) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3063683D1 (en) * | 1979-08-24 | 1983-07-14 | Beecham Group Plc | Amine salt of clavulanic acid, its preparation and use |
| EP0042220B1 (en) * | 1980-06-11 | 1984-08-15 | Beecham Group Plc | Process for the preparation of beta-lactam antibiotics |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2635477A1 (de) * | 1975-08-20 | 1977-03-03 | Beecham Group Ltd | Verfahren zur herstellung fester, praktisch reiner natrium- und kaliumsalze der clavulansaeure |
-
1977
- 1977-01-19 GB GB2031/77A patent/GB1572912A/en not_active Expired
-
1978
- 1978-01-09 BE BE184209A patent/BE862764A/xx not_active IP Right Cessation
- 1978-01-11 FR FR7800673A patent/FR2378035A1/fr active Granted
- 1978-01-14 JP JP323178A patent/JPS5390289A/ja active Pending
- 1978-01-18 NL NL7800604A patent/NL7800604A/xx not_active Application Discontinuation
- 1978-01-18 DE DE19782802049 patent/DE2802049A1/de not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| DE2802049A1 (de) | 1978-07-20 |
| BE862764A (fr) | 1978-07-10 |
| FR2378035A1 (fr) | 1978-08-18 |
| JPS5390289A (en) | 1978-08-08 |
| FR2378035B1 (en, 2012) | 1982-11-19 |
| NL7800604A (nl) | 1978-07-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0098545B1 (en) | Epimerization of malonic acid esters | |
| US5064961A (en) | Process for preparing an optically active cyclobutane nucleoside | |
| EP0005889B1 (en) | Process for the preparation of beta-lactam derivatives, the novel derivatives so obtainable and pharmaceutical compositions containing them | |
| US6013828A (en) | Processes and intermediates useful to make antifolates | |
| US4734512A (en) | Intermediates for the production of podophyllotoxin and related compounds and processes for the preparation and use thereof | |
| EP0023097B1 (en) | De-arylmethylation of n-mono- or n-diarylmethyl-beta-lactams; novel azetizinones having anti-bacterial activity | |
| DD156533A5 (de) | Verfahren zur herstellung von 3-iodmethylcephalosporinen | |
| EP0037592A2 (en) | Beta-lactam compounds | |
| US3522266A (en) | 5-hydroxythiazolidines | |
| GB1572912A (en) | Clavulanic acid esters | |
| JP2648472B2 (ja) | β−ラクタム化合物及びその製造方法 | |
| EP0111286B1 (en) | Novel beta-lactam derivatives and process for production thereof | |
| US4440682A (en) | Stereospecific synthesis of isocephalosporins and 2-oxa isocephalosporins | |
| Gasco et al. | Alkyl N‐methylfuroxanylcarbamates. Synthesis and structure. II | |
| US4443599A (en) | 8-Oxo-3-oxa-1-azabicyclo[4.2.0]octanes containing a chiral center | |
| US4148995A (en) | Process for preparing cephem lactones for cephalosporin-type antibiotics | |
| EP0135683B1 (en) | Method for production of cephalosporin compounds | |
| US4162251A (en) | Process for the preparation of β-lactam compounds | |
| EP0002370B1 (en) | A process for the preparation of ether derivatives of clavulanic acid | |
| US4448732A (en) | 2-Oxo-1,3-dioxol-4-ylmethyl esters of penicillanic acid 1,1-dioxide | |
| KR870000313B1 (ko) | 6-(아미노메틸)페니실란산 1,1-다이옥사이드 및 이의 유도체의 제조방법 | |
| US5256806A (en) | Intermediates for the preparation of optically active cyclobutane nucleoside | |
| US4438265A (en) | Esters of 7-sulfenyliminocephem-4-carboxylic acids | |
| US4210751A (en) | Process for producing 7β-amino-7α-methoxycephalosporins | |
| EP0009302B1 (en) | Clavulanic acid derivatives and process for their preparation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PS | Patent sealed | ||
| PCNP | Patent ceased through non-payment of renewal fee |