CN1315841C - 制备氯甲基头孢烯衍生物的改进方法 - Google Patents
制备氯甲基头孢烯衍生物的改进方法 Download PDFInfo
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- CN1315841C CN1315841C CNB2003801023937A CN200380102393A CN1315841C CN 1315841 C CN1315841 C CN 1315841C CN B2003801023937 A CNB2003801023937 A CN B2003801023937A CN 200380102393 A CN200380102393 A CN 200380102393A CN 1315841 C CN1315841 C CN 1315841C
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- China
- Prior art keywords
- formula
- methoxybenzyl
- solvent
- acid
- substituted
- 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 - Fee Related
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- 238000000034 method Methods 0.000 title claims abstract description 27
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- QNJLADIWFYPULV-NQPNHJOESA-N (6r)-4-(chloromethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-en-8-one Chemical class C1=CC(CCl)S[C@@H]2CC(=O)N21 QNJLADIWFYPULV-NQPNHJOESA-N 0.000 title claims abstract description 13
- 239000001257 hydrogen Substances 0.000 claims abstract description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 4
- 125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 4
- 125000002927 2-methoxybenzyl group Chemical group [H]C1=C([H])C([H])=C(C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 claims abstract description 4
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims abstract description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 4
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 claims abstract description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims abstract description 4
- 125000006239 protecting group Chemical group 0.000 claims abstract description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 42
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 33
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 24
- 239000002904 solvent Substances 0.000 claims description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 20
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 17
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 15
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 14
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 12
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 11
- 150000001875 compounds Chemical class 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 10
- 238000007363 ring formation reaction Methods 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 7
- 229910021529 ammonia Inorganic materials 0.000 claims description 7
- 239000012320 chlorinating reagent Substances 0.000 claims description 7
- 229910052751 metal Inorganic materials 0.000 claims description 7
- 239000002184 metal Substances 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 claims description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 5
- 239000000460 chlorine Substances 0.000 claims description 5
- ZJAIXMWQDVXMLZ-UHFFFAOYSA-L copper;4-methylbenzenesulfinate Chemical compound [Cu+2].CC1=CC=C(S([O-])=O)C=C1.CC1=CC=C(S([O-])=O)C=C1 ZJAIXMWQDVXMLZ-UHFFFAOYSA-L 0.000 claims description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- RCJVRSBWZCNNQT-UHFFFAOYSA-N dichloridooxygen Chemical compound ClOCl RCJVRSBWZCNNQT-UHFFFAOYSA-N 0.000 claims description 4
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 claims description 4
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 claims description 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 3
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 3
- 235000010216 calcium carbonate Nutrition 0.000 claims description 3
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims description 3
- 239000011736 potassium bicarbonate Substances 0.000 claims description 3
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 3
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- 235000011181 potassium carbonates Nutrition 0.000 claims description 3
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- 235000017550 sodium carbonate Nutrition 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims description 2
- 239000005695 Ammonium acetate Substances 0.000 claims description 2
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- SKVCFOFOWALKJJ-UHFFFAOYSA-L [Ag+2].CC1=CC=C(S([O-])=O)C=C1.CC1=CC=C(S([O-])=O)C=C1 Chemical compound [Ag+2].CC1=CC=C(S([O-])=O)C=C1.CC1=CC=C(S([O-])=O)C=C1 SKVCFOFOWALKJJ-UHFFFAOYSA-L 0.000 claims description 2
- PVFDEIKMUYEPMS-UHFFFAOYSA-L [Ag+2].[O-]S(=O)C1=CC=CC=C1.[O-]S(=O)C1=CC=CC=C1 Chemical compound [Ag+2].[O-]S(=O)C1=CC=CC=C1.[O-]S(=O)C1=CC=CC=C1 PVFDEIKMUYEPMS-UHFFFAOYSA-L 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 229940043376 ammonium acetate Drugs 0.000 claims description 2
- 235000019257 ammonium acetate Nutrition 0.000 claims description 2
- 239000001099 ammonium carbonate Substances 0.000 claims description 2
- 235000012501 ammonium carbonate Nutrition 0.000 claims description 2
- 150000003863 ammonium salts Chemical class 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- JHCPRMVDOCTAMG-UHFFFAOYSA-L copper;benzenesulfinate Chemical compound [Cu+2].[O-]S(=O)C1=CC=CC=C1.[O-]S(=O)C1=CC=CC=C1 JHCPRMVDOCTAMG-UHFFFAOYSA-L 0.000 claims description 2
- QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 claims description 2
- UCFFGYASXIPWPD-UHFFFAOYSA-N methyl hypochlorite Chemical compound COCl UCFFGYASXIPWPD-UHFFFAOYSA-N 0.000 claims description 2
- 238000012986 modification Methods 0.000 claims description 2
- 230000004048 modification Effects 0.000 claims description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims 4
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims 1
- 150000001298 alcohols Chemical class 0.000 claims 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims 1
- 229910001882 dioxygen Inorganic materials 0.000 claims 1
- CHLCPTJLUJHDBO-UHFFFAOYSA-M sodium;benzenesulfinate Chemical compound [Na+].[O-]S(=O)C1=CC=CC=C1 CHLCPTJLUJHDBO-UHFFFAOYSA-M 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract description 4
- 150000001555 benzenes Chemical group 0.000 abstract 1
- -1 carboxylate ion Chemical class 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 17
- 239000011541 reaction mixture Substances 0.000 description 15
- 239000012044 organic layer Substances 0.000 description 14
- 239000002585 base Substances 0.000 description 11
- HFNGYHHRRMSKEU-UHFFFAOYSA-N 4-Methoxybenzyl acetate Chemical compound COC1=CC=C(COC(C)=O)C=C1 HFNGYHHRRMSKEU-UHFFFAOYSA-N 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 9
- YXIWHUQXZSMYRE-UHFFFAOYSA-N 1,3-benzothiazole-2-thiol Chemical group C1=CC=C2SC(S)=NC2=C1 YXIWHUQXZSMYRE-UHFFFAOYSA-N 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 239000002002 slurry Substances 0.000 description 8
- 238000003756 stirring Methods 0.000 description 7
- BFPVQCSLPMODTF-UHFFFAOYSA-N 3-sulfonylazetidin-2-one Chemical class O=C1NCC1=S(=O)=O BFPVQCSLPMODTF-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000012535 impurity Substances 0.000 description 5
- KFCMZNUGNLCSJQ-GWQXNCQPSA-N (4-methoxyphenyl)methyl (6r)-3-(chloromethyl)-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1=CC(OC)=CC=C1COC(=O)C1=C(CCl)CS[C@H]2N1C(=O)C2NC(=O)CC1=CC=CC=C1 KFCMZNUGNLCSJQ-GWQXNCQPSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 229930186147 Cephalosporin Natural products 0.000 description 4
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 4
- 229940124587 cephalosporin Drugs 0.000 description 4
- 150000001780 cephalosporins Chemical class 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- YMEXAAFKFVBTPW-UHFFFAOYSA-N 1-(chloromethyl)azetidin-2-one Chemical class ClCN1CCC1=O YMEXAAFKFVBTPW-UHFFFAOYSA-N 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- JJHPQGFGFRPCCH-UHFFFAOYSA-N acetic acid;butane Chemical compound CCCC.CC(O)=O JJHPQGFGFRPCCH-UHFFFAOYSA-N 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- 239000003610 charcoal Substances 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 238000007429 general method Methods 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 235000011837 pasties Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 3
- 235000019345 sodium thiosulphate Nutrition 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- WHERMLSFDXCIQO-WPZCJLIBSA-N (6r)-3-(chloromethyl)-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C1([C@H]2SCC(CCl)=C(N2C1=O)C(=O)O)NC(=O)CC1=CC=CC=C1 WHERMLSFDXCIQO-WPZCJLIBSA-N 0.000 description 2
- DWDDFMFCVGDERN-UHFFFAOYSA-N 1-chloroazetidin-2-one Chemical compound ClN1CCC1=O DWDDFMFCVGDERN-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 238000005660 chlorination reaction Methods 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 125000001072 heteroaryl group Chemical group 0.000 description 2
- 229960001082 trimethoprim Drugs 0.000 description 2
- REJZMNMWWGNGIJ-SSDOTTSWSA-N (6r)-3-(chloromethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-en-8-one Chemical compound S1CC(CCl)=CN2C(=O)C[C@H]21 REJZMNMWWGNGIJ-SSDOTTSWSA-N 0.000 description 1
- YHMYGUUIMTVXNW-UHFFFAOYSA-N 1,3-dihydrobenzimidazole-2-thione Chemical group C1=CC=C2NC(S)=NC2=C1 YHMYGUUIMTVXNW-UHFFFAOYSA-N 0.000 description 1
- KYWXRBNOYGGPIZ-UHFFFAOYSA-N 1-morpholin-4-ylethanone Chemical compound CC(=O)N1CCOCC1 KYWXRBNOYGGPIZ-UHFFFAOYSA-N 0.000 description 1
- FLFWJIBUZQARMD-UHFFFAOYSA-N 2-mercapto-1,3-benzoxazole Chemical group C1=CC=C2OC(S)=NC2=C1 FLFWJIBUZQARMD-UHFFFAOYSA-N 0.000 description 1
- BOYNILPHVAYVGO-UHFFFAOYSA-N 3-(chloromethyl)azetidin-2-one Chemical class ClCC1CNC1=O BOYNILPHVAYVGO-UHFFFAOYSA-N 0.000 description 1
- HDFGFMYFTNSFER-UHFFFAOYSA-N 5-methyl-2-sulfanyltetrazole Chemical group CC=1N=NN(S)N=1 HDFGFMYFTNSFER-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- HJPOKQICBCJGHE-UHFFFAOYSA-J [C+4].[Cl-].[Cl-].[Cl-].[Cl-] Chemical compound [C+4].[Cl-].[Cl-].[Cl-].[Cl-] HJPOKQICBCJGHE-UHFFFAOYSA-J 0.000 description 1
- 125000005036 alkoxyphenyl group Chemical group 0.000 description 1
- 125000005037 alkyl phenyl group Chemical group 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 150000001782 cephems Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229910001902 chlorine oxide Inorganic materials 0.000 description 1
- MAYPHUUCLRDEAZ-UHFFFAOYSA-N chlorine peroxide Chemical compound ClOOCl MAYPHUUCLRDEAZ-UHFFFAOYSA-N 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 231100001261 hazardous Toxicity 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- LCEDQNDDFOCWGG-UHFFFAOYSA-N morpholine-4-carbaldehyde Chemical compound O=CN1CCOCC1 LCEDQNDDFOCWGG-UHFFFAOYSA-N 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 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
- C07D501/02—Preparation
- C07D501/08—Preparation by forming the ring or condensed ring systems
-
- 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
-
- 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)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Cephalosporin Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN808/MAS/2002 | 2002-11-01 | ||
| IN808CH2002 | 2002-11-01 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1708501A CN1708501A (zh) | 2005-12-14 |
| CN1315841C true CN1315841C (zh) | 2007-05-16 |
Family
ID=35561711
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2003801023937A Expired - Fee Related CN1315841C (zh) | 2002-11-01 | 2003-10-23 | 制备氯甲基头孢烯衍生物的改进方法 |
Country Status (5)
| Country | Link |
|---|---|
| JP (1) | JP2006507289A (enrdf_load_stackoverflow) |
| KR (1) | KR20050087791A (enrdf_load_stackoverflow) |
| CN (1) | CN1315841C (enrdf_load_stackoverflow) |
| AU (1) | AU2003269416A1 (enrdf_load_stackoverflow) |
| WO (1) | WO2004039813A1 (enrdf_load_stackoverflow) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1666483B1 (en) * | 2003-09-09 | 2011-08-17 | Nippon Chemical Industrial Company Limited | Process for producing 3-chloromethyl-3-cephem derivative |
| CN101260116A (zh) * | 2008-04-21 | 2008-09-10 | 湖南有色凯铂生物药业有限公司 | 7-苯乙酰胺-3-氯甲基-4-头孢烷酸对甲氧苄酯的合成方法 |
| CN102344459B (zh) * | 2011-07-27 | 2014-08-06 | 山西新天源医药化工有限公司 | 一种头孢中间体gcle的制备方法 |
| CN102643294B (zh) * | 2012-04-18 | 2014-11-26 | 山东普洛得邦医药有限公司 | 一种头孢母核中间体的制备方法 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4789740A (en) * | 1983-03-10 | 1988-12-06 | Otsuka Kagaku Yakuhin Kabushiki Kaisha | Halogenation process for preparing 2-(oxoazetidinyl)-3-chloromethyl-3-butenoate |
| US4853468A (en) * | 1981-04-10 | 1989-08-01 | Otsuka Kagaku Yakuhin Kabushiki Kaisha | Process for the preparation of cephem derivatives |
| EP0623622A1 (en) * | 1992-07-27 | 1994-11-09 | Otsuka Kagaku Kabushiki Kaisha | Process for producing cephem compound |
| WO1998055485A1 (fr) * | 1997-06-04 | 1998-12-10 | Otsuka Kagaku Kabushiki Kaisha | Procede de production de composes de 3-alcenylcephem |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IE35152B1 (en) * | 1969-08-26 | 1975-11-26 | Glaxo Lab Ltd | Improvements in or relating to cephalosporin compounds |
| NL7411505A (nl) * | 1973-09-06 | 1975-03-10 | Rhone Poulenc Sa | Werkwijze voor de bereiding en toepassing van nieuwe 7-trichlooraceetamido-3-desacetoxy-cefa- losporanzuurpreparaten. |
| AU498131B2 (en) * | 1974-02-26 | 1979-02-15 | Ciba-Geigy Ag | Production of cephems by cyclization |
| JPS5874689A (ja) * | 1981-10-29 | 1983-05-06 | Otsuka Chem Co Ltd | ３−クロロメチル−３−セフエム誘導体の製造法 |
| JPS6043340B2 (ja) * | 1981-04-10 | 1985-09-27 | 大塚化学薬品株式会社 | 塩素化アゼチジノン誘導体及びその製造法 |
| JPS60115562A (ja) * | 1983-11-28 | 1985-06-22 | Otsuka Chem Co Ltd | アゼチジノン誘導体の製造法 |
| JPS60237061A (ja) * | 1984-05-08 | 1985-11-25 | Otsuka Chem Co Ltd | アゼチジノン誘導体の製造法 |
| DE3933934A1 (de) * | 1989-10-03 | 1991-04-11 | Bayer Ag | Verfahren zur herstellung von 7-amino-3-((z)-1-propen-1-yl)-3-cephem-4-carbonsaeure |
-
2003
- 2003-10-23 AU AU2003269416A patent/AU2003269416A1/en not_active Abandoned
- 2003-10-23 WO PCT/IB2003/004721 patent/WO2004039813A1/en active Application Filing
- 2003-10-23 CN CNB2003801023937A patent/CN1315841C/zh not_active Expired - Fee Related
- 2003-10-23 KR KR1020057007694A patent/KR20050087791A/ko not_active Withdrawn
- 2003-10-23 JP JP2004547902A patent/JP2006507289A/ja active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4853468A (en) * | 1981-04-10 | 1989-08-01 | Otsuka Kagaku Yakuhin Kabushiki Kaisha | Process for the preparation of cephem derivatives |
| US4789740A (en) * | 1983-03-10 | 1988-12-06 | Otsuka Kagaku Yakuhin Kabushiki Kaisha | Halogenation process for preparing 2-(oxoazetidinyl)-3-chloromethyl-3-butenoate |
| EP0623622A1 (en) * | 1992-07-27 | 1994-11-09 | Otsuka Kagaku Kabushiki Kaisha | Process for producing cephem compound |
| WO1998055485A1 (fr) * | 1997-06-04 | 1998-12-10 | Otsuka Kagaku Kabushiki Kaisha | Procede de production de composes de 3-alcenylcephem |
Non-Patent Citations (1)
| Title |
|---|
| COPPER(I) BENZENESULFINATE AND COPPER(I)P-TOLUENESULFINATE BERTZ ET AL:,INORGANIC CHEMISTRY,Vol.24 No.21 1985 * |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2003269416A1 (en) | 2004-05-25 |
| CN1708501A (zh) | 2005-12-14 |
| WO2004039813A1 (en) | 2004-05-13 |
| JP2006507289A (ja) | 2006-03-02 |
| KR20050087791A (ko) | 2005-08-31 |
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