DE2819511A1 - Neue ester von cephem-verbindungen, verfahren zu deren herstellung und methode zur entfernung der schutzgruppe - Google Patents
Neue ester von cephem-verbindungen, verfahren zu deren herstellung und methode zur entfernung der schutzgruppeInfo
- Publication number
- DE2819511A1 DE2819511A1 DE19782819511 DE2819511A DE2819511A1 DE 2819511 A1 DE2819511 A1 DE 2819511A1 DE 19782819511 DE19782819511 DE 19782819511 DE 2819511 A DE2819511 A DE 2819511A DE 2819511 A1 DE2819511 A1 DE 2819511A1
- Authority
- DE
- Germany
- Prior art keywords
- group
- hydrogen atom
- substituted
- chloride
- heterocyclic
- 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.)
- Ceased
Links
- -1 CEPHEM COMPOUNDS Chemical class 0.000 title claims description 75
- 238000000034 method Methods 0.000 title claims description 39
- 238000004519 manufacturing process Methods 0.000 title description 4
- 230000001681 protective effect Effects 0.000 title 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 39
- 125000000623 heterocyclic group Chemical group 0.000 claims description 33
- 125000006239 protecting group Chemical group 0.000 claims description 32
- 125000004432 carbon atom Chemical group C* 0.000 claims description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 28
- 150000002148 esters Chemical class 0.000 claims description 27
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 23
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 18
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 18
- 150000001875 compounds Chemical class 0.000 claims description 18
- 229910052717 sulfur Inorganic materials 0.000 claims description 16
- 125000004149 thio group Chemical group *S* 0.000 claims description 15
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 13
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- 239000001301 oxygen Substances 0.000 claims description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 12
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- 239000011593 sulfur Substances 0.000 claims description 12
- 150000001782 cephems Chemical class 0.000 claims description 11
- 125000003277 amino group Chemical group 0.000 claims description 10
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 10
- 239000002841 Lewis acid Substances 0.000 claims description 9
- 150000007517 lewis acids Chemical class 0.000 claims description 9
- BIAAQBNMRITRDV-UHFFFAOYSA-N 1-(chloromethoxy)-2-methoxyethane Chemical compound COCCOCCl BIAAQBNMRITRDV-UHFFFAOYSA-N 0.000 claims description 8
- 125000004104 aryloxy group Chemical group 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 claims description 7
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 125000004423 acyloxy group Chemical group 0.000 claims description 5
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 5
- 125000003435 aroyl group Chemical group 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 5
- 125000004414 alkyl thio group Chemical group 0.000 claims description 4
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 150000005846 sugar alcohols Polymers 0.000 claims description 4
- 125000004434 sulfur atom Chemical group 0.000 claims description 4
- 229910052783 alkali metal Inorganic materials 0.000 claims description 3
- 150000001340 alkali metals Chemical class 0.000 claims description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 3
- 150000001342 alkaline earth metals Chemical class 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 239000012442 inert solvent Substances 0.000 claims description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 150000001298 alcohols Chemical class 0.000 claims description 2
- 239000002585 base Substances 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims 3
- 101150052863 THY1 gene Proteins 0.000 claims 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 81
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
- 238000006243 chemical reaction Methods 0.000 description 30
- 239000000203 mixture Substances 0.000 description 22
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- 239000010410 layer Substances 0.000 description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 15
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
- 239000012044 organic layer Substances 0.000 description 12
- 229960000603 cefalotin Drugs 0.000 description 10
- VUFGUVLLDPOSBC-XRZFDKQNSA-M cephalothin sodium Chemical compound [Na+].N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC(=O)C)C([O-])=O)C(=O)CC1=CC=CS1 VUFGUVLLDPOSBC-XRZFDKQNSA-M 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 9
- 238000005886 esterification reaction Methods 0.000 description 9
- 238000000862 absorption spectrum Methods 0.000 description 8
- 125000001424 substituent group Chemical group 0.000 description 8
- 239000012141 concentrate Substances 0.000 description 7
- 239000013078 crystal Substances 0.000 description 7
- 230000032050 esterification Effects 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 235000017557 sodium bicarbonate Nutrition 0.000 description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- HOKIDJSKDBPKTQ-GLXFQSAKSA-N cephalosporin C Chemical compound S1CC(COC(=O)C)=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CCC[C@@H](N)C(O)=O)[C@@H]12 HOKIDJSKDBPKTQ-GLXFQSAKSA-N 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 229930186147 Cephalosporin Natural products 0.000 description 5
- 229940124587 cephalosporin Drugs 0.000 description 5
- 150000001780 cephalosporins Chemical class 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- 238000004821 distillation Methods 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 238000001228 spectrum Methods 0.000 description 5
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000001819 mass spectrum Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical compound Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 150000004820 halides Chemical class 0.000 description 3
- 238000006317 isomerization reaction Methods 0.000 description 3
- LGLXXNHIGIJYQQ-UHFFFAOYSA-L magnesium;dibromide;hexahydrate Chemical compound O.O.O.O.O.O.[Mg+2].[Br-].[Br-] LGLXXNHIGIJYQQ-UHFFFAOYSA-L 0.000 description 3
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
- 150000007530 organic bases Chemical class 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 2
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000001361 adipic acid Substances 0.000 description 2
- 235000011037 adipic acid Nutrition 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 125000004799 bromophenyl group Chemical group 0.000 description 2
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- FLKYBGKDCCEQQM-WYUVZMMLSA-M cefazolin sodium Chemical compound [Na+].S1C(C)=NN=C1SCC1=C(C([O-])=O)N2C(=O)[C@@H](NC(=O)CN3N=NN=C3)[C@H]2SC1 FLKYBGKDCCEQQM-WYUVZMMLSA-M 0.000 description 2
- ZAIPMKNFIOOWCQ-UEKVPHQBSA-N cephalexin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 ZAIPMKNFIOOWCQ-UEKVPHQBSA-N 0.000 description 2
- 229940106164 cephalexin Drugs 0.000 description 2
- 150000001793 charged compounds Chemical class 0.000 description 2
- 125000004803 chlorobenzyl group Chemical group 0.000 description 2
- 125000000068 chlorophenyl group Chemical group 0.000 description 2
- 238000010924 continuous production Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 125000004464 hydroxyphenyl group Chemical group 0.000 description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- 125000006178 methyl benzyl group Chemical group 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000012429 reaction media Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Chemical compound O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000005924 transacylation reaction Methods 0.000 description 2
- 229940102001 zinc bromide Drugs 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- UDTVQXNZIKQKOI-BAFYGKSASA-N (6r)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-4-carboxylic acid Chemical compound C1=CC(C(=O)O)S[C@@H]2CC(=O)N21 UDTVQXNZIKQKOI-BAFYGKSASA-N 0.000 description 1
- 125000001917 2,4-dinitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1*)[N+]([O-])=O)[N+]([O-])=O 0.000 description 1
- SBASXUCJHJRPEV-UHFFFAOYSA-N 2-(2-methoxyethoxy)ethanol Chemical compound COCCOCCO SBASXUCJHJRPEV-UHFFFAOYSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 1
- AOPRXJXHLWYPQR-UHFFFAOYSA-N 2-phenoxyacetamide Chemical compound NC(=O)COC1=CC=CC=C1 AOPRXJXHLWYPQR-UHFFFAOYSA-N 0.000 description 1
- SMJRBWINMFUUDS-UHFFFAOYSA-N 2-thienylacetic acid Chemical class OC(=O)CC1=CC=CS1 SMJRBWINMFUUDS-UHFFFAOYSA-N 0.000 description 1
- 125000000242 4-chlorobenzoyl group Chemical group ClC1=CC=C(C(=O)*)C=C1 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 235000003197 Byrsonima crassifolia Nutrition 0.000 description 1
- 240000001546 Byrsonima crassifolia Species 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- 229910021592 Copper(II) chloride Inorganic materials 0.000 description 1
- FHIJMQWMMZEFBL-HLAPJUAOSA-N DISS Natural products COc1cc(C=CC(=O)OC[C@H]2O[C@H](O[C@]3(CO)O[C@H](CO)[C@@H](O)[C@@H]3OC(=O)C=Cc3cc(OC)c(O)c(OC)c3)[C@H](O)[C@@H](O)[C@@H]2O)cc(OC)c1O FHIJMQWMMZEFBL-HLAPJUAOSA-N 0.000 description 1
- BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 229910021577 Iron(II) chloride Inorganic materials 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 229910021586 Nickel(II) chloride Inorganic materials 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 238000006136 alcoholysis reaction Methods 0.000 description 1
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 125000005239 aroylamino group Chemical group 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- OEERIBPGRSLGEK-UHFFFAOYSA-N carbon dioxide;methanol Chemical compound OC.O=C=O OEERIBPGRSLGEK-UHFFFAOYSA-N 0.000 description 1
- 125000004112 carboxyamino group Chemical group [H]OC(=O)N([H])[*] 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 229960001139 cefazolin Drugs 0.000 description 1
- MLYYVTUWGNIJIB-BXKDBHETSA-N cefazolin Chemical compound S1C(C)=NN=C1SCC1=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CN3N=NN=C3)[C@H]2SC1 MLYYVTUWGNIJIB-BXKDBHETSA-N 0.000 description 1
- 229960003408 cefazolin sodium Drugs 0.000 description 1
- YGBFLZPYDUKSPT-MRVPVSSYSA-N cephalosporanic acid Chemical class S1CC(COC(=O)C)=C(C(O)=O)N2C(=O)C[C@H]21 YGBFLZPYDUKSPT-MRVPVSSYSA-N 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 description 1
- GVPFVAHMJGGAJG-UHFFFAOYSA-L cobalt dichloride Chemical compound [Cl-].[Cl-].[Co+2] GVPFVAHMJGGAJG-UHFFFAOYSA-L 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 description 1
- 150000002484 inorganic compounds Chemical class 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- NMCUIPGRVMDVDB-UHFFFAOYSA-L iron dichloride Chemical compound Cl[Fe]Cl NMCUIPGRVMDVDB-UHFFFAOYSA-L 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 description 1
- 229910001623 magnesium bromide Inorganic materials 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical compound [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 description 1
- QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 description 1
- AIYYMMQIMJOTBM-UHFFFAOYSA-L nickel(ii) acetate Chemical compound [Ni+2].CC([O-])=O.CC([O-])=O AIYYMMQIMJOTBM-UHFFFAOYSA-L 0.000 description 1
- ODUCDPQEXGNKDN-UHFFFAOYSA-N nitroxyl Chemical compound O=N ODUCDPQEXGNKDN-UHFFFAOYSA-N 0.000 description 1
- 150000002902 organometallic compounds Chemical class 0.000 description 1
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 description 1
- JLGLQAWTXXGVEM-UHFFFAOYSA-N triethylene glycol monomethyl ether Chemical compound COCCOCCOCCO JLGLQAWTXXGVEM-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- RKBCYCFRFCNLTO-UHFFFAOYSA-N triisopropylamine Chemical compound CC(C)N(C(C)C)C(C)C RKBCYCFRFCNLTO-UHFFFAOYSA-N 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
- C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
- C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
-
- 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)
- Cephalosporin Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5068877A JPS53137986A (en) | 1977-05-04 | 1977-05-04 | Novel esters of cephem compounds and process for their preparation |
| JP5068977A JPS53137987A (en) | 1977-05-04 | 1977-05-04 | Esters of cephem compounds and process for their preparation |
| JP10356277A JPS5448782A (en) | 1977-08-31 | 1977-08-31 | Deesterification of cephem compound ester |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2819511A1 true DE2819511A1 (de) | 1978-11-09 |
Family
ID=27294045
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19782819511 Ceased DE2819511A1 (de) | 1977-05-04 | 1978-05-03 | Neue ester von cephem-verbindungen, verfahren zu deren herstellung und methode zur entfernung der schutzgruppe |
Country Status (5)
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE71383T1 (de) * | 1984-11-15 | 1992-01-15 | Hoffmann La Roche | Verfahren zur herstellung von cephalosporinestern. |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE784800A (fr) * | 1971-06-15 | 1972-10-02 | Yamanouchi Pharma Co Ltd | Procede de preparation de nouveaux derives esters oxymethyliques de la penicilline et de la cephalosporine |
| JPS5417030B2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) * | 1972-12-06 | 1979-06-27 | ||
| JPS5513719B2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) * | 1972-12-06 | 1980-04-10 | ||
| JPS512477A (en) * | 1974-06-25 | 1976-01-10 | Zekoo Kk | Ijokeisha shindonokanchisochi |
-
1978
- 1978-04-21 US US05/898,613 patent/US4225706A/en not_active Expired - Lifetime
- 1978-04-26 GB GB16454/78A patent/GB1594890A/en not_active Expired
- 1978-05-03 FR FR7813181A patent/FR2389632B1/fr not_active Expired
- 1978-05-03 IT IT22980/78A patent/IT1096261B/it active
- 1978-05-03 DE DE19782819511 patent/DE2819511A1/de not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| FR2389632B1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1983-10-07 |
| GB1594890A (en) | 1981-08-05 |
| US4225706A (en) | 1980-09-30 |
| FR2389632A1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1978-12-01 |
| IT1096261B (it) | 1985-08-26 |
| IT7822980A0 (it) | 1978-05-03 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| OAP | Request for examination filed | ||
| OD | Request for examination | ||
| 8131 | Rejection |