NO783180L - Fremgangsmaate for fremstilling av clavulansyre-etere - Google Patents

Fremgangsmaate for fremstilling av clavulansyre-etere

Info

Publication number: NO783180L
Authority: NO; Norway
Prior art keywords: group; formula; ester; salt; compound
Prior art date: 1977-09-20

Application number

NO783180A

Other languages

English (en)

Norwegian (no)

Inventor

Thomas Trefor Howarth

Eric Hunt

Original Assignee

Beecham Group Ltd

Priority date (The priority date 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 date listed.)

1977-09-20

Filing date

1978-09-19

Publication date

1979-03-21

1978-09-19 Application filed by Beecham Group Ltd filed Critical Beecham Group Ltd

1979-03-21 Publication of NO783180L publication Critical patent/NO783180L/no

Links

HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 title claims description 56
-1 CLAVULANIC ACID ETHERS Chemical class 0.000 title claims description 45
238000000034 method Methods 0.000 title claims description 41
229960003324 clavulanic acid Drugs 0.000 title claims description 23
150000001875 compounds Chemical class 0.000 claims description 126
150000003839 salts Chemical class 0.000 claims description 79
125000000217 alkyl group Chemical group 0.000 claims description 62
150000002148 esters Chemical class 0.000 claims description 55
HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 claims description 54
238000002360 preparation method Methods 0.000 claims description 41
125000004432 carbon atom Chemical group C* 0.000 claims description 31
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 28
125000003118 aryl group Chemical group 0.000 claims description 27
229910052739 hydrogen Inorganic materials 0.000 claims description 22
239000001257 hydrogen Substances 0.000 claims description 22
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
125000003710 aryl alkyl group Chemical group 0.000 claims description 21
239000011734 sodium Substances 0.000 claims description 21
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 20
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
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 19
229910052708 sodium Inorganic materials 0.000 claims description 19
LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 claims description 17
229960003022 amoxicillin Drugs 0.000 claims description 16
LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 claims description 16
125000003545 alkoxy group Chemical group 0.000 claims description 14
238000006243 chemical reaction Methods 0.000 claims description 14
229910052801 chlorine Inorganic materials 0.000 claims description 14
AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 claims description 12
230000008569 process Effects 0.000 claims description 12
125000003277 amino group Chemical group 0.000 claims description 11
229960000723 ampicillin Drugs 0.000 claims description 10
229910052731 fluorine Inorganic materials 0.000 claims description 10
239000011737 fluorine Substances 0.000 claims description 10
239000002253 acid Substances 0.000 claims description 8
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
229930182555 Penicillin Natural products 0.000 claims description 7
239000000460 chlorine Chemical group 0.000 claims description 7
238000004519 manufacturing process Methods 0.000 claims description 7
229930186147 Cephalosporin Natural products 0.000 claims description 6
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 claims description 6
229940124587 cephalosporin Drugs 0.000 claims description 6
150000001780 cephalosporins Chemical class 0.000 claims description 6
238000005984 hydrogenation reaction Methods 0.000 claims description 6
230000007062 hydrolysis Effects 0.000 claims description 6
238000006460 hydrolysis reaction Methods 0.000 claims description 6
230000002195 synergetic effect Effects 0.000 claims description 6
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 5
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
229910052794 bromium Inorganic materials 0.000 claims description 5
238000007257 deesterification reaction Methods 0.000 claims description 5
239000011591 potassium Substances 0.000 claims description 5
229910052700 potassium Inorganic materials 0.000 claims description 5
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 4
125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 4
125000001153 fluoro group Chemical group F* 0.000 claims description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
229910052744 lithium Inorganic materials 0.000 claims description 4
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
229940049954 penicillin Drugs 0.000 claims description 4
239000000825 pharmaceutical preparation Substances 0.000 claims description 4
YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical class CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 claims description 4
125000005843 halogen group Chemical group 0.000 claims description 3
239000011777 magnesium Substances 0.000 claims description 3
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 2
125000004423 acyloxy group Chemical group 0.000 claims description 2
125000003342 alkenyl group Chemical group 0.000 claims description 2
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 2
239000003781 beta lactamase inhibitor Substances 0.000 claims description 2
229940126813 beta-lactamase inhibitor Drugs 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
229910052749 magnesium Inorganic materials 0.000 claims description 2
239000000651 prodrug Substances 0.000 claims description 2
229940002612 prodrug Drugs 0.000 claims description 2
229940126085 β‑Lactamase Inhibitor Drugs 0.000 claims description 2
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 123
239000000243 solution Substances 0.000 description 94
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 79
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 76
229940090805 clavulanate Drugs 0.000 description 68
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 53
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 42
239000002904 solvent Substances 0.000 description 41
239000000203 mixture Substances 0.000 description 39
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 38
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 33
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 31
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
239000000706 filtrate Substances 0.000 description 24
239000000741 silica gel Substances 0.000 description 24
229910002027 silica gel Inorganic materials 0.000 description 24
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 23
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
238000001914 filtration Methods 0.000 description 22
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 20
239000000843 powder Substances 0.000 description 19
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 18
239000003054 catalyst Substances 0.000 description 18
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
238000001704 evaporation Methods 0.000 description 17
235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 15
244000166102 Eucalyptus leucoxylon Species 0.000 description 15
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
AZUFHGGGPUUXKI-FLFDDASRSA-N benzyl (2r,3z,5r)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylate Chemical compound O=C([C@@H]1N2C(=O)C[C@H]2O\C1=C/CO)OCC1=CC=CC=C1 AZUFHGGGPUUXKI-FLFDDASRSA-N 0.000 description 15
230000008020 evaporation Effects 0.000 description 15
239000003208 petroleum Substances 0.000 description 13
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 12
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
239000012298 atmosphere Substances 0.000 description 12
239000000047 product Substances 0.000 description 12
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
239000002585 base Substances 0.000 description 10
239000003921 oil Substances 0.000 description 10
239000002244 precipitate Substances 0.000 description 10
235000017557 sodium bicarbonate Nutrition 0.000 description 9
229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
239000007787 solid Substances 0.000 description 9
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 8
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 7
229960000583 acetic acid Drugs 0.000 description 7
125000001309 chloro group Chemical group Cl* 0.000 description 7
238000010828 elution Methods 0.000 description 7
208000015181 infectious disease Diseases 0.000 description 7
YZYKBQUWMPUVEN-UHFFFAOYSA-N zafuleptine Chemical compound OC(=O)CCCCCC(C(C)C)NCC1=CC=C(F)C=C1 YZYKBQUWMPUVEN-UHFFFAOYSA-N 0.000 description 7
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 6
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
125000002015 acyclic group Chemical group 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
230000000694 effects Effects 0.000 description 6
IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 6
239000000543 intermediate Substances 0.000 description 6
229910052943 magnesium sulfate Inorganic materials 0.000 description 6
235000019341 magnesium sulphate Nutrition 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
241000699670 Mus sp. Species 0.000 description 5
230000007717 exclusion Effects 0.000 description 5
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 5
159000000000 sodium salts Chemical class 0.000 description 5
XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 4
241000588724 Escherichia coli Species 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
230000000844 anti-bacterial effect Effects 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
238000010533 azeotropic distillation Methods 0.000 description 4
YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 4
239000003814 drug Substances 0.000 description 4
SHZIWNPUGXLXDT-UHFFFAOYSA-N ethyl hexanoate Chemical compound CCCCCC(=O)OCC SHZIWNPUGXLXDT-UHFFFAOYSA-N 0.000 description 4
239000012362 glacial acetic acid Substances 0.000 description 4
238000007327 hydrogenolysis reaction Methods 0.000 description 4
238000002347 injection Methods 0.000 description 4
239000007924 injection Substances 0.000 description 4
229910003002 lithium salt Inorganic materials 0.000 description 4
159000000002 lithium salts Chemical class 0.000 description 4
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
UOUBPDZUBVJZOQ-UHFFFAOYSA-N n-(hydroxymethyl)benzamide Chemical compound OCNC(=O)C1=CC=CC=C1 UOUBPDZUBVJZOQ-UHFFFAOYSA-N 0.000 description 4
229910052763 palladium Inorganic materials 0.000 description 4
DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 4
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 4
229910052938 sodium sulfate Inorganic materials 0.000 description 4
235000011152 sodium sulphate Nutrition 0.000 description 4
239000000725 suspension Substances 0.000 description 4
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
CPLXHLVBOLITMK-UHFFFAOYSA-N Magnesium oxide Chemical compound [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
230000009102 absorption Effects 0.000 description 3
238000010521 absorption reaction Methods 0.000 description 3
150000001412 amines Chemical class 0.000 description 3
239000003242 anti bacterial agent Substances 0.000 description 3
125000004104 aryloxy group Chemical group 0.000 description 3
238000003556 assay Methods 0.000 description 3
239000011575 calcium Substances 0.000 description 3
229910052791 calcium Inorganic materials 0.000 description 3
229910052799 carbon Inorganic materials 0.000 description 3
239000013078 crystal Substances 0.000 description 3
238000005868 electrolysis reaction Methods 0.000 description 3
150000002170 ethers Chemical class 0.000 description 3
159000000003 magnesium salts Chemical class 0.000 description 3
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
231100000252 nontoxic Toxicity 0.000 description 3
230000003000 nontoxic effect Effects 0.000 description 3
150000002960 penicillins Chemical class 0.000 description 3
238000012360 testing method Methods 0.000 description 3
238000001665 trituration Methods 0.000 description 3
239000004246 zinc acetate Substances 0.000 description 3
235000013904 zinc acetate Nutrition 0.000 description 3
KGQWVTVYDXKBKH-UHFFFAOYSA-N 1-formamidoethyl acetate Chemical compound O=CNC(C)OC(C)=O KGQWVTVYDXKBKH-UHFFFAOYSA-N 0.000 description 2
241000894006 Bacteria Species 0.000 description 2
KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
101150041968 CDC13 gene Proteins 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
BSEYWXDBSOCPQP-UHFFFAOYSA-N Saltillin Natural products C1=CC(OC)=CC=C1C1=CC(=O)C2=C(O)C=C(C)C=C2O1 BSEYWXDBSOCPQP-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 2
UIXSASZBPZYESC-PWSUYJOCSA-N [(2s,3s)-4-oxo-3-(phenylmethoxycarbonylamino)azetidin-2-yl] acetate Chemical compound CC(=O)O[C@@H]1NC(=O)[C@H]1NC(=O)OCC1=CC=CC=C1 UIXSASZBPZYESC-PWSUYJOCSA-N 0.000 description 2
BSIJPSKAVILORK-UHFFFAOYSA-N [[2-(phenylmethoxycarbonylamino)acetyl]amino]methyl acetate Chemical compound CC(=O)OCNC(=O)CNC(=O)OCC1=CC=CC=C1 BSIJPSKAVILORK-UHFFFAOYSA-N 0.000 description 2
ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 description 2
229910052784 alkaline earth metal Inorganic materials 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
229940040526 anhydrous sodium acetate Drugs 0.000 description 2
229940088710 antibiotic agent Drugs 0.000 description 2
125000004429 atom Chemical group 0.000 description 2
TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
UBTLDRGTYJCOJQ-UHFFFAOYSA-N benzamidomethyl acetate Chemical compound CC(=O)OCNC(=O)C1=CC=CC=C1 UBTLDRGTYJCOJQ-UHFFFAOYSA-N 0.000 description 2
239000003782 beta lactam antibiotic agent Substances 0.000 description 2
230000003115 biocidal effect Effects 0.000 description 2
230000036765 blood level Effects 0.000 description 2
WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 2
239000000920 calcium hydroxide Substances 0.000 description 2
235000011116 calcium hydroxide Nutrition 0.000 description 2
229910001861 calcium hydroxide Inorganic materials 0.000 description 2
FPPNZSSZRUTDAP-UWFZAAFLSA-N carbenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)C(C(O)=O)C1=CC=CC=C1 FPPNZSSZRUTDAP-UWFZAAFLSA-N 0.000 description 2
229960003669 carbenicillin Drugs 0.000 description 2
125000002843 carboxylic acid group Chemical group 0.000 description 2
125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 2
239000003729 cation exchange resin Substances 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
239000012230 colorless oil Substances 0.000 description 2
238000004440 column chromatography Methods 0.000 description 2
238000010511 deprotection reaction Methods 0.000 description 2
150000008049 diazo compounds Chemical class 0.000 description 2
150000002081 enamines Chemical class 0.000 description 2
238000006266 etherification reaction Methods 0.000 description 2
239000012065 filter cake Substances 0.000 description 2
239000011521 glass Substances 0.000 description 2
150000004820 halides Chemical class 0.000 description 2
238000010348 incorporation Methods 0.000 description 2
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229920005989 resin Polymers 0.000 description 1
210000002345 respiratory system Anatomy 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
235000017550 sodium carbonate Nutrition 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 1
210000004872 soft tissue Anatomy 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000000547 substituted alkyl group Chemical group 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000003826 tablet Substances 0.000 description 1
QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical class C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
210000001635 urinary tract Anatomy 0.000 description 1
238000005406 washing Methods 0.000 description 1
238000005303 weighing Methods 0.000 description 1
DJWUNCQRNNEAKC-UHFFFAOYSA-L zinc acetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O DJWUNCQRNNEAKC-UHFFFAOYSA-L 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/22—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/06—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D205/08—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
- C07D205/085—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams with a nitrogen atom directly attached in position 3
- 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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Life Sciences & Earth Sciences (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Communicable Diseases (AREA)
Pharmacology & Pharmacy (AREA)
Oncology (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

NO783180A 1977-09-20 1978-09-19 Fremgangsmaate for fremstilling av clavulansyre-etere NO783180L (no)

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date	Title
GB3904077		1977-09-20
GB3925177		1977-09-21
GB7826989		1978-06-15
GB7827497		1978-06-21
GB7828209		1978-06-28

Publications (1)

Publication Number	Publication Date
NO783180L true NO783180L (no)	1979-03-21

Family

ID=27516339

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO783180A NO783180L (no)	1977-09-20	1978-09-19	Fremgangsmaate for fremstilling av clavulansyre-etere

Country Status (13)

Country	Link
EP (1)	EP0001333B1 (ja)
JP (1)	JPS5455593A (ja)
AR (1)	AR222640A1 (ja)
AT (1)	AT364847B (ja)
AU (1)	AU3994278A (ja)
CA (1)	CA1105467A (ja)
DE (1)	DE2862030D1 (ja)
DK (1)	DK415378A (ja)
FI (1)	FI782852A7 (ja)
GR (1)	GR65659B (ja)
IT (1)	IT7851133A0 (ja)
NO (1)	NO783180L (ja)
PT (1)	PT68553A (ja)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ATE1550T1 (de) *	1978-09-05	1982-09-15	Beecham Group Plc	Clavulansaeurederivate, ihre herstellung und sie enthaltende pharmazeutische zusammensetzungen.
EP0046349A1 (en) *	1980-08-16	1982-02-24	Beecham Group Plc	Clavulanic acid derivatives, their preparation and use

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB1546569A (en) *	1975-07-29	1979-05-23	Beecham Group Ltd	1-oxa-1-dethiapenicillins methods for their preparation and compositions containing them
GB1565209A (en) *	1975-10-13	1980-04-16	Beecham Group Ltd	Clavulanic acid derivatives

1978
- 1978-08-30 DE DE7878300328T patent/DE2862030D1/de not_active Expired
- 1978-08-30 EP EP78300328A patent/EP0001333B1/en not_active Expired
- 1978-08-31 CA CA310,472A patent/CA1105467A/en not_active Expired
- 1978-09-12 AR AR273660A patent/AR222640A1/es active
- 1978-09-14 AT AT0663978A patent/AT364847B/de not_active IP Right Cessation
- 1978-09-14 PT PT68553A patent/PT68553A/pt unknown
- 1978-09-18 GR GR57257A patent/GR65659B/el unknown
- 1978-09-18 FI FI782852A patent/FI782852A7/fi unknown
- 1978-09-18 AU AU39942/78A patent/AU3994278A/en active Pending
- 1978-09-18 IT IT7851133A patent/IT7851133A0/it unknown
- 1978-09-19 DK DK415378A patent/DK415378A/da unknown
- 1978-09-19 NO NO783180A patent/NO783180L/no unknown
- 1978-09-20 JP JP11646478A patent/JPS5455593A/ja active Pending

Also Published As

Publication number	Publication date
DE2862030D1 (en)	1982-11-04
ATA663978A (de)	1981-04-15
EP0001333B1 (en)	1982-09-15
PT68553A (en)	1978-10-01
AT364847B (de)	1981-11-25
EP0001333A1 (en)	1979-04-04
IT7851133A0 (it)	1978-09-18
FI782852A7 (fi)	1979-03-21
GR65659B (en)	1980-10-16
AR222640A1 (es)	1981-06-15
DK415378A (da)	1979-03-21
AU3994278A (en)	1980-03-27
CA1105467A (en)	1981-07-21
JPS5455593A (en)	1979-05-02

Publication	Publication Date	Title
IE46877B1 (en)	1983-10-19	Thienamycin derivatives
NO802661L (no)	1977-04-14	Analogifremgangsmaate for fremstilling av antibakterielt virksomme klavulansyrederivater
US4244965A (en)	1981-01-13	Azetidinoyl ethers
US4155912A (en)	1979-05-22	2-Methylpenem-3-carboxylic acid antibiotics
NO781372L (no)	1978-10-24	Fremgangsmaate for fremstilling av antibakterielle midler
US4215128A (en)	1980-07-29	Clavulanic acid derivatives their preparation and use
US4263302A (en)	1981-04-21	Quinolinecarboxylic acid substituted penicillins and pharmaceutical compositions containing the same
NO783180L (no)	1979-03-21	Fremgangsmaate for fremstilling av clavulansyre-etere
IE45559B1 (en)	1982-09-22	Lactam antibiotics
NO833842L (no)	1977-07-14	Mellomprodukter for fremstilling av klavulansyreetere
GB1585124A (en)	1981-02-25	Clavulanic acid derivatives
US4258050A (en)	1981-03-24	Antibacterial agents
GB1573503A (en)	1980-08-28	Clavulanic acid derivatives
GB1570987A (en)	1980-07-09	Thienamycin derivatives
US4372946A (en)	1983-02-08	Clavulanic acid derivatives their preparation and use
GB1595176A (en)	1981-08-12	Clavulanic acid ethers
IE42707B1 (en)	1980-10-08	6-methoxy-6-( -carboxy thienylacetamido)-penicillins
DE2751041A1 (de)	1978-05-24	Beta-lactame, verfahren zu ihrer herstellung und ihre verwendung bei der behandlung bakterieller infektionen
US4349551A (en)	1982-09-14	Penicillin derivatives and compositions containing them
IE55225B1 (en)	1990-07-04	Carbapenem antibiotics
US4540580A (en)	1985-09-10	2-[(1'R)-1'-Aminoalkyl]penems
NO833416L (no)	1983-07-12	Penicillansyre-1,1-dioksyd-derivater
US4427689A (en)	1984-01-24	Clavulanic acid 9-deoxy-9-thia derivatives their preparation and use
US4169833A (en)	1979-10-02	Novel phosphorane intermediates for use in preparing penem antibiotics
EP0023093B1 (en)	1983-09-28	Penicillanic acid derivatives, their preparation and their pharmaceutical compositions with a penicillin or cephalosporin