CA1240985A - Preparation de cephalosporines - Google Patents

Preparation de cephalosporines

Info

Publication number: CA1240985A
Authority: CA; Canada
Prior art keywords: alkyl; formula; denotes; phenyl; radical
Prior art date: 1981-11-19
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

Application number

CA000541405A

Other languages

English (en)

Inventor

Gunther Kinast

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Bayer AG

Original Assignee

Bayer AG

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.)

1981-11-19

Filing date

1987-07-06

Publication date

1988-08-23

1981-11-19 Priority claimed from DE19813145727 external-priority patent/DE3145727A1/de

1986-03-26 Priority claimed from CA000505254A external-priority patent/CA1238911A/fr

1987-07-06 Application filed by Bayer AG filed Critical Bayer AG

1987-07-06 Priority to CA000541405A priority Critical patent/CA1240985A/fr

1988-08-23 Application granted granted Critical

1988-08-23 Publication of CA1240985A publication Critical patent/CA1240985A/fr

Status Expired legal-status Critical Current

Links

150000001780 cephalosporins Chemical class 0.000 title abstract description 9
229930186147 Cephalosporin Natural products 0.000 title abstract description 8
229940124587 cephalosporin Drugs 0.000 title abstract description 8
238000002360 preparation method Methods 0.000 title description 30
-1 formyloxymethyl Chemical group 0.000 claims abstract description 83
150000001875 compounds Chemical class 0.000 claims abstract description 78
125000000217 alkyl group Chemical group 0.000 claims abstract description 44
239000002253 acid Substances 0.000 claims abstract description 32
229910052736 halogen Inorganic materials 0.000 claims abstract description 21
125000003118 aryl group Chemical group 0.000 claims abstract description 20
150000002367 halogens Chemical class 0.000 claims abstract description 20
239000001257 hydrogen Substances 0.000 claims abstract description 19
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 19
125000003342 alkenyl group Chemical group 0.000 claims abstract description 15
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 15
125000003545 alkoxy group Chemical group 0.000 claims abstract description 9
229910052801 chlorine Inorganic materials 0.000 claims abstract description 9
125000000392 cycloalkenyl group Chemical group 0.000 claims abstract description 6
125000002837 carbocyclic group Chemical group 0.000 claims abstract description 4
YGBFLZPYDUKSPT-MRVPVSSYSA-N cephalosporanic acid Chemical compound S1CC(COC(=O)C)=C(C(O)=O)N2C(=O)C[C@H]21 YGBFLZPYDUKSPT-MRVPVSSYSA-N 0.000 claims abstract description 4
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims abstract description 4
229910052794 bromium Inorganic materials 0.000 claims abstract description 3
150000002431 hydrogen Chemical class 0.000 claims abstract 5
239000000203 mixture Substances 0.000 claims description 33
125000001424 substituent group Chemical group 0.000 claims description 32
125000004432 carbon atom Chemical group C* 0.000 claims description 30
238000000034 method Methods 0.000 claims description 25
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 17
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
150000003254 radicals Chemical class 0.000 claims description 16
239000000460 chlorine Substances 0.000 claims description 12
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
150000002148 esters Chemical class 0.000 claims description 9
125000006239 protecting group Chemical group 0.000 claims description 8
238000007127 saponification reaction Methods 0.000 claims description 8
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 7
238000004519 manufacturing process Methods 0.000 claims description 7
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
125000005842 heteroatom Chemical group 0.000 claims description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
230000008878 coupling Effects 0.000 claims description 5
238000010168 coupling process Methods 0.000 claims description 5
238000005859 coupling reaction Methods 0.000 claims description 5
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
229910052799 carbon Inorganic materials 0.000 claims description 4
229910052731 fluorine Inorganic materials 0.000 claims description 4
239000011737 fluorine Substances 0.000 claims description 4
125000001153 fluoro group Chemical group F* 0.000 claims description 4
125000000623 heterocyclic group Chemical group 0.000 claims description 4
125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 claims description 4
125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 3
125000004414 alkyl thio group Chemical group 0.000 claims description 3
125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 3
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 2
CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
150000007513 acids Chemical class 0.000 abstract description 9
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 63
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 42
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
239000000243 solution Substances 0.000 description 26
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 25
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 22
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
229940073584 methylene chloride Drugs 0.000 description 21
238000006243 chemical reaction Methods 0.000 description 19
239000002585 base Substances 0.000 description 16
239000002904 solvent Substances 0.000 description 16
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
238000002844 melting Methods 0.000 description 13
230000008018 melting Effects 0.000 description 13
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
239000012071 phase Substances 0.000 description 12
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 9
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
239000000047 product Substances 0.000 description 8
150000002500 ions Chemical class 0.000 description 7
229940086542 triethylamine Drugs 0.000 description 7
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 6
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
239000011591 potassium Substances 0.000 description 6
229910052700 potassium Inorganic materials 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
229910052757 nitrogen Inorganic materials 0.000 description 5
238000000926 separation method Methods 0.000 description 5
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
150000001299 aldehydes Chemical class 0.000 description 4
150000001412 amines Chemical class 0.000 description 4
150000008064 anhydrides Chemical class 0.000 description 4
238000001816 cooling Methods 0.000 description 4
238000006317 isomerization reaction Methods 0.000 description 4
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
238000005481 NMR spectroscopy Methods 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
150000001735 carboxylic acids Chemical class 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
229940043279 diisopropylamine Drugs 0.000 description 3
229960001760 dimethyl sulfoxide Drugs 0.000 description 3
125000005982 diphenylmethyl group Chemical class [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
WINCJOWZQAVIPN-UHFFFAOYSA-N tert-butyl 4-(2-ethoxy-2-oxoethyl)-2-[(2-methylpropan-2-yl)oxycarbonylimino]-1,3-thiazole-3-carboxylate Chemical compound CCOC(=O)CC1=CSC(=NC(=O)OC(C)(C)C)N1C(=O)OC(C)(C)C WINCJOWZQAVIPN-UHFFFAOYSA-N 0.000 description 3
238000010626 work up procedure Methods 0.000 description 3
HSHGZXNAXBPPDL-IOJJLOCKSA-N (6r)-3-(acetyloxymethyl)-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound S1CC(COC(=O)C)=C(C(O)=O)N2C(=O)C(N)[C@@H]12 HSHGZXNAXBPPDL-IOJJLOCKSA-N 0.000 description 2
NDVMCQUOSYOQMZ-UHFFFAOYSA-N 2,2-bis(trimethylsilyl)acetamide Chemical compound C[Si](C)(C)C(C(N)=O)[Si](C)(C)C NDVMCQUOSYOQMZ-UHFFFAOYSA-N 0.000 description 2
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
YGHRJJRRZDOVPD-UHFFFAOYSA-N 3-methylbutanal Chemical compound CC(C)CC=O YGHRJJRRZDOVPD-UHFFFAOYSA-N 0.000 description 2
101150041968 CDC13 gene Proteins 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
AMIMRNSIRUDHCM-UHFFFAOYSA-N Isopropylaldehyde Chemical compound CC(C)C=O AMIMRNSIRUDHCM-UHFFFAOYSA-N 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
239000005864 Sulphur Substances 0.000 description 2
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
150000001408 amides Chemical class 0.000 description 2
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
238000001035 drying Methods 0.000 description 2
SHQNGLYXRFCPGZ-UHFFFAOYSA-N ethyl 2-(2-amino-1,3-thiazol-4-yl)acetate Chemical compound CCOC(=O)CC1=CSC(N)=N1 SHQNGLYXRFCPGZ-UHFFFAOYSA-N 0.000 description 2
238000000605 extraction Methods 0.000 description 2
FXHGMKSSBGDXIY-UHFFFAOYSA-N heptanal Chemical compound CCCCCCC=O FXHGMKSSBGDXIY-UHFFFAOYSA-N 0.000 description 2
JARKCYVAAOWBJS-UHFFFAOYSA-N hexanal Chemical compound CCCCCC=O JARKCYVAAOWBJS-UHFFFAOYSA-N 0.000 description 2
150000004678 hydrides Chemical class 0.000 description 2
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 2
HGBOYTHUEUWSSQ-UHFFFAOYSA-N pentanal Chemical compound CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
238000003756 stirring Methods 0.000 description 2
125000000547 substituted alkyl group Chemical group 0.000 description 2
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 2
238000005406 washing Methods 0.000 description 2
NIONDZDPPYHYKY-SNAWJCMRSA-N (2E)-hexenoic acid Chemical compound CCC\C=C\C(O)=O NIONDZDPPYHYKY-SNAWJCMRSA-N 0.000 description 1
PDVFSPNIEOYOQL-UHFFFAOYSA-N (4-methylphenyl)sulfonyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OS(=O)(=O)C1=CC=C(C)C=C1 PDVFSPNIEOYOQL-UHFFFAOYSA-N 0.000 description 1
ZZJNYZZMWBXNON-SSDOTTSWSA-N (6R)-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound CN1N=NN=C1SCC=1CS[C@H]2N(C=1C(=O)O)C(C2)=O ZZJNYZZMWBXNON-SSDOTTSWSA-N 0.000 description 1
XUTQHTOXGKVJPN-XCGJVMPOSA-N (6r)-7-amino-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound CN1N=NN=C1SCC1=C(C(O)=O)N2C(=O)C(N)[C@H]2SC1 XUTQHTOXGKVJPN-XCGJVMPOSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
ZLTWIJREHQCJJL-UHFFFAOYSA-N 1-trimethylsilylethanol Chemical compound CC(O)[Si](C)(C)C ZLTWIJREHQCJJL-UHFFFAOYSA-N 0.000 description 1
238000005160 1H NMR spectroscopy Methods 0.000 description 1
DYCLHZPOADTVKK-UHFFFAOYSA-N 2-(2-azaniumyl-1,3-thiazol-4-yl)acetate Chemical compound NC1=NC(CC(O)=O)=CS1 DYCLHZPOADTVKK-UHFFFAOYSA-N 0.000 description 1
GYIWRVHTKIHMAE-UHFFFAOYSA-N 2-trimethylsilylethyl 2-(2-amino-1,3-thiazol-4-yl)acetate Chemical compound C[Si](C)(C)CCOC(=O)CC1=CSC(N)=N1 GYIWRVHTKIHMAE-UHFFFAOYSA-N 0.000 description 1
JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 1
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 1
241000269350 Anura Species 0.000 description 1
ZTQSAGDEMFDKMZ-UHFFFAOYSA-N Butyraldehyde Chemical compound CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 1
HNUALPPJLMYHDK-UHFFFAOYSA-N C[CH]C Chemical compound C[CH]C HNUALPPJLMYHDK-UHFFFAOYSA-N 0.000 description 1
OKTJSMMVPCPJKN-IGMARMGPSA-N Carbon-12 Chemical group [12C] OKTJSMMVPCPJKN-IGMARMGPSA-N 0.000 description 1
241000192125 Firmicutes Species 0.000 description 1
241000694408 Isomeris Species 0.000 description 1
DBTDEFJAFBUGPP-UHFFFAOYSA-N Methanethial Chemical compound S=C DBTDEFJAFBUGPP-UHFFFAOYSA-N 0.000 description 1
238000006845 Michael addition reaction Methods 0.000 description 1
239000007832 Na2SO4 Substances 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
101100162169 Xenopus laevis adrm1-a gene Proteins 0.000 description 1
IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 1
229940022682 acetone Drugs 0.000 description 1
230000004913 activation Effects 0.000 description 1
230000010933 acylation Effects 0.000 description 1
238000005917 acylation reaction Methods 0.000 description 1
239000003513 alkali Substances 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
230000000844 anti-bacterial effect Effects 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
150000005840 aryl radicals Chemical class 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
238000009835 boiling Methods 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
229960001701 chloroform Drugs 0.000 description 1
239000000306 component Substances 0.000 description 1
235000019628 coolness Nutrition 0.000 description 1
LDHQCZJRKDOVOX-NSCUHMNNSA-N crotonic acid Chemical compound C\C=C\C(O)=O LDHQCZJRKDOVOX-NSCUHMNNSA-N 0.000 description 1
FFYPMLJYZAEMQB-UHFFFAOYSA-N diethyl pyrocarbonate Chemical compound CCOC(=O)OC(=O)OCC FFYPMLJYZAEMQB-UHFFFAOYSA-N 0.000 description 1
IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
238000004821 distillation Methods 0.000 description 1
239000003792 electrolyte Substances 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
125000004185 ester group Chemical group 0.000 description 1
IPCKVUWARYCCAK-UHFFFAOYSA-N ethyl 2-ethoxycarbonylimino-4-(2-ethoxy-2-oxoethyl)-1,3-thiazole-3-carboxylate Chemical compound CCOC(=O)CC1=CSC(=NC(=O)OCC)N1C(=O)OCC IPCKVUWARYCCAK-UHFFFAOYSA-N 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000007717 exclusion Effects 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
238000001914 filtration Methods 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
239000005457 ice water Substances 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
239000013067 intermediate product Substances 0.000 description 1
LDHQCZJRKDOVOX-IHWYPQMZSA-N isocrotonic acid Chemical compound C\C=C/C(O)=O LDHQCZJRKDOVOX-IHWYPQMZSA-N 0.000 description 1
239000007788 liquid Substances 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
239000000463 material Substances 0.000 description 1
IZDROVVXIHRYMH-UHFFFAOYSA-N methanesulfonic anhydride Chemical compound CS(=O)(=O)OS(C)(=O)=O IZDROVVXIHRYMH-UHFFFAOYSA-N 0.000 description 1
WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical class [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 description 1
HCBPHBQMSDVIPZ-UHFFFAOYSA-N methylcyclohexatriene Chemical compound CC1=CC=C=C[CH]1 HCBPHBQMSDVIPZ-UHFFFAOYSA-N 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
125000002524 organometallic group Chemical group 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
230000020477 pH reduction Effects 0.000 description 1
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
VFQXVTODMYMSMJ-UHFFFAOYSA-O pyridin-1-ium-4-carboxamide Chemical compound NC(=O)C1=CC=[NH+]C=C1 VFQXVTODMYMSMJ-UHFFFAOYSA-O 0.000 description 1
239000000376 reactant Substances 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000010992 reflux Methods 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
238000006884 silylation reaction Methods 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000007787 solid Substances 0.000 description 1
125000003107 substituted aryl group Chemical group 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical class OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 1
JCCOWQFRHBUOEX-UHFFFAOYSA-N tert-butyl 2-(2-amino-1,3-thiazol-4-yl)acetate Chemical compound CC(C)(C)OC(=O)CC1=CSC(N)=N1 JCCOWQFRHBUOEX-UHFFFAOYSA-N 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
125000001302 tertiary amino group Chemical group 0.000 description 1
IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
NEYRPZPFGJCJDL-UHFFFAOYSA-N trimethylsilyl 2-(2-amino-1,3-thiazol-4-yl)acetate Chemical compound C[Si](C)(C)OC(=O)CC1=CSC(N)=N1 NEYRPZPFGJCJDL-UHFFFAOYSA-N 0.000 description 1
238000010792 warming Methods 0.000 description 1

Landscapes

Cephalosporin Compounds (AREA)

CA000541405A 1981-11-19 1987-07-06 Preparation de cephalosporines Expired CA1240985A (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA000541405A CA1240985A (fr)	1981-11-19	1987-07-06	Preparation de cephalosporines

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date	Title
DE19813145727 DE3145727A1 (de)	1981-11-19	1981-11-19	Zwischenprodukte, verfahren zu deren herstellung und verfahren zur herstellung von cephalosporinen
DEP3145727.4		1981-11-19
CA000415708A CA1212949A (fr)	1981-11-19	1982-11-17	Produits intermediaires, procede pour leur preparation et procede de preparation de cephalosporines
CA000505254A CA1238911A (fr)	1981-11-19	1986-03-26	Derives de substitution d'aminothiazole
CA000541405A CA1240985A (fr)	1981-11-19	1987-07-06	Preparation de cephalosporines

Related Parent Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000505254A Division CA1238911A (fr)	1981-11-19	1986-03-26	Derives de substitution d'aminothiazole

Publications (1)

Publication Number	Publication Date
CA1240985A true CA1240985A (fr)	1988-08-23

Family

ID=27167303

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
CA000541405A Expired CA1240985A (fr)	1981-11-19	1987-07-06	Preparation de cephalosporines
CA000541321A Expired CA1247109A (fr)	1981-11-19	1987-07-06	Intermediaires pour la preparation des cephalosporines et leur preparation

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
CA000541321A Expired CA1247109A (fr)	1981-11-19	1987-07-06	Intermediaires pour la preparation des cephalosporines et leur preparation

Country Status (1)

Country	Link
CA (2)	CA1240985A (fr)

1987
- 1987-07-06 CA CA000541405A patent/CA1240985A/fr not_active Expired
- 1987-07-06 CA CA000541321A patent/CA1247109A/fr not_active Expired

Also Published As

Publication number	Publication date
CA1247109A (fr)	1988-12-20

Legal Events

Date	Code	Title	Description
2005-08-23	MKEX	Expiry

Publication	Publication Date	Title
US4500716A (en)	1985-02-19	Intermediate products for the preparation of Z-cephalosporins
CA1192193A (fr)	1985-08-20	Epimerisation d'esters d'acide malonique
US4298529A (en)	1981-11-03	Alkoxyimino dioxy butyric acid derivatives
EP0082498B1 (fr)	1989-11-02	Dérivés bêta-lactame et procédé pour leur préparation
AU690482B2 (en)	1998-04-23	Process for producing cephalosporin antibiotics
US4888429A (en)	1989-12-19	Process for producing allyl aminothiazole acetate intermediates
CA1238911A (fr)	1988-07-05	Derives de substitution d'aminothiazole
EP0397212B1 (fr)	1996-01-10	Procédé de préparation de céphalosporines
CA1247109A (fr)	1988-12-20	Intermediaires pour la preparation des cephalosporines et leur preparation
KR880001540B1 (ko)	1988-08-20	세팔로스포린의 제조방법
US4379923A (en)	1983-04-12	Preparation of 7-acylamino-3-(thio-substituted)-methyl 3-cephem-4-carboxylic acid-1-oxide derivatives
KR880001761B1 (ko)	1988-09-12	세팔로스포린 제조용 중간체의 제조방법
KR880001760B1 (ko)	1988-09-12	세팔로스포린 제조용 중간체의 제조방법
US4558124A (en)	1985-12-10	Preparation of cephalosporin intermediate compounds
US4379922A (en)	1983-04-12	Cepham compounds
JPH0358351B2 (fr)	1991-09-05
GB2173502A (en)	1986-10-15	New thiadiazole compounds and processes for their preparation
JPH0354110B2 (fr)	1991-08-19
JPH0577670B2 (fr)	1993-10-27
JPH0662635B2 (ja)	1994-08-17	セフアロスポリン類の新規製造法
JPH0217550B2 (fr)	1990-04-20
JPH0517229B2 (fr)	1993-03-08
JPH0362713B2 (fr)	1991-09-26
JPH0140826B2 (fr)	1989-08-31
JPH024227B2 (fr)	1990-01-26