IE44133B1 - Process for preparing 2-cephem compounds - Google Patents
Process for preparing 2-cephem compoundsInfo
- Publication number
- IE44133B1 IE44133B1 IE2598/76A IE259876A IE44133B1 IE 44133 B1 IE44133 B1 IE 44133B1 IE 2598/76 A IE2598/76 A IE 2598/76A IE 259876 A IE259876 A IE 259876A IE 44133 B1 IE44133 B1 IE 44133B1
- Authority
- IE
- Ireland
- Prior art keywords
- carboxylate
- formula
- nitrobenzyl
- cephem
- oxide
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 4
- SXBDXXFTJVHSAF-ZCFIWIBFSA-N (6r)-5-thia-1-azabicyclo[4.2.0]oct-3-en-8-one Chemical class S1C=CCN2C(=O)C[C@H]21 SXBDXXFTJVHSAF-ZCFIWIBFSA-N 0.000 title 1
- 239000000203 mixture Substances 0.000 claims abstract description 45
- 150000008064 anhydrides Chemical class 0.000 claims abstract description 16
- 150000003855 acyl compounds Chemical class 0.000 claims abstract description 9
- -1 cyano, trifluoroethyl Chemical group 0.000 claims description 119
- 238000000034 method Methods 0.000 claims description 63
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 50
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 33
- 150000003462 sulfoxides Chemical class 0.000 claims description 24
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 22
- 238000006243 chemical reaction Methods 0.000 claims description 18
- 125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 claims description 17
- 125000006244 carboxylic acid protecting group Chemical group 0.000 claims description 13
- 150000001875 compounds Chemical class 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical group CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims description 8
- 239000012346 acetyl chloride Substances 0.000 claims description 8
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 8
- XAKBSHICSHRJCL-UHFFFAOYSA-N [CH2]C(=O)C1=CC=CC=C1 Chemical group [CH2]C(=O)C1=CC=CC=C1 XAKBSHICSHRJCL-UHFFFAOYSA-N 0.000 claims description 7
- 239000003960 organic solvent Substances 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 6
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
- 125000005042 acyloxymethyl group Chemical group 0.000 claims description 4
- 235000019260 propionic acid Nutrition 0.000 claims description 4
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 claims description 4
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 4
- 125000002030 1,2-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([*:2])C([H])=C1[H] 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000003368 amide group Chemical group 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 125000000018 nitroso group Chemical group N(=O)* 0.000 claims description 3
- 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 150000003254 radicals Chemical class 0.000 claims description 3
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 125000004970 halomethyl group Chemical group 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims 1
- 229930186147 Cephalosporin Natural products 0.000 abstract description 13
- 229940124587 cephalosporin Drugs 0.000 abstract description 13
- 150000001780 cephalosporins Chemical class 0.000 abstract description 11
- 238000002360 preparation method Methods 0.000 abstract description 10
- 239000000543 intermediate Substances 0.000 abstract description 6
- ATTZFSUZZUNHBP-UHFFFAOYSA-N Piperonyl sulfoxide Chemical compound CCCCCCCCS(=O)C(C)CC1=CC=C2OCOC2=C1 ATTZFSUZZUNHBP-UHFFFAOYSA-N 0.000 abstract 1
- 230000003115 biocidal effect Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- 239000000047 product Substances 0.000 description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 239000002253 acid Substances 0.000 description 14
- 239000000243 solution Substances 0.000 description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- 239000007858 starting material Substances 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- 150000002148 esters Chemical class 0.000 description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 8
- NGHVIOIJCVXTGV-ALEPSDHESA-N 6-aminopenicillanic acid Chemical compound [O-]C(=O)[C@H]1C(C)(C)S[C@@H]2[C@H]([NH3+])C(=O)N21 NGHVIOIJCVXTGV-ALEPSDHESA-N 0.000 description 7
- NGHVIOIJCVXTGV-UHFFFAOYSA-N 6beta-amino-penicillanic acid Natural products OC(=O)C1C(C)(C)SC2C(N)C(=O)N21 NGHVIOIJCVXTGV-UHFFFAOYSA-N 0.000 description 7
- UBOXGVDOUJQMTN-UHFFFAOYSA-N 1,1,2-trichloroethane Chemical compound ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 0.000 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 description 6
- 238000003776 cleavage reaction Methods 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 230000007017 scission Effects 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- 229930182555 Penicillin Natural products 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 238000007363 ring formation reaction Methods 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 150000008065 acid anhydrides Chemical class 0.000 description 4
- 150000001263 acyl chlorides Chemical class 0.000 description 4
- 239000003242 anti bacterial agent Substances 0.000 description 4
- 229940088710 antibiotic agent Drugs 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 238000005886 esterification reaction Methods 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 229940049954 penicillin Drugs 0.000 description 4
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 239000002841 Lewis acid Substances 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 3
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 3
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 230000032050 esterification Effects 0.000 description 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 150000007517 lewis acids Chemical class 0.000 description 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 2
- JYJIMEQNTHFXMT-UHFFFAOYSA-N 2-nitro-2-phenylacetic acid Chemical compound OC(=O)C([N+]([O-])=O)C1=CC=CC=C1 JYJIMEQNTHFXMT-UHFFFAOYSA-N 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 125000004450 alkenylene group Chemical group 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- ZRRLCCCOCSDAKF-UHFFFAOYSA-N azetidin-2-one thionyl dichloride Chemical compound ClS(Cl)=O.O=C1CCN1 ZRRLCCCOCSDAKF-UHFFFAOYSA-N 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
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 230000002140 halogenating effect Effects 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
- 238000006317 isomerization reaction Methods 0.000 description 2
- URMOIQPAWQIYLI-NQPNHJOESA-N methyl (6R)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2-carboxylate Chemical compound COC(=O)C1C=CS[C@H]2N1C(C2)=O URMOIQPAWQIYLI-NQPNHJOESA-N 0.000 description 2
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
- VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical compound Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- CCCFDSYQPTWYSL-XMFHEBTDSA-N (2,5-dioxopyrrolidin-1-yl)methyl (6R)-3-methylidene-5,8-dioxo-7-[[2-(1,3-thiazol-2-yl)acetyl]amino]-5lambda4-thia-1-azabicyclo[4.2.0]octane-2-carboxylate Chemical compound C1([C@H]2S(=O)CC(C(N2C1=O)C(=O)OCN1C(CCC1=O)=O)=C)NC(=O)CC1=NC=CS1 CCCFDSYQPTWYSL-XMFHEBTDSA-N 0.000 description 1
- PAYVGOBLTIUYNX-QETWGEEDSA-N (2,5-dioxopyrrolidin-1-yl)methyl (6R)-8-oxo-3-(pentanoyloxymethyl)-7-[[2-(1,3-thiazol-2-yl)acetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2-carboxylate Chemical compound S1C(=NC=C1)CC(=O)NC1[C@@H]2N(C(C(=CS2)COC(CCCC)=O)C(=O)OCN2C(CCC2=O)=O)C1=O PAYVGOBLTIUYNX-QETWGEEDSA-N 0.000 description 1
- USBIHDPRWDYQAT-FRQOBSDTSA-N (4-methoxyphenyl)methyl (6R)-3-methylidene-5,8-dioxo-7-[(3-oxo-3-phenacyloxy-2-phenylpropanoyl)amino]-5lambda4-thia-1-azabicyclo[4.2.0]octane-2-carboxylate Chemical compound C(C(=O)C1=CC=CC=C1)OC(=O)C(C(=O)NC1[C@@H]2N(C(C(CS2=O)=C)C(=O)OCC2=CC=C(C=C2)OC)C1=O)C1=CC=CC=C1 USBIHDPRWDYQAT-FRQOBSDTSA-N 0.000 description 1
- PSECYZRZTXNZQB-PEEKXZHXSA-N (4-methoxyphenyl)methyl (6R)-7-[[2-(furan-2-yl)acetyl]amino]-3-methylidene-5,8-dioxo-5lambda4-thia-1-azabicyclo[4.2.0]octane-2-carboxylate Chemical compound C1=CC(OC)=CC=C1COC(=O)C1C(=C)CS(=O)[C@H]2N1C(=O)C2NC(=O)CC1=CC=CO1 PSECYZRZTXNZQB-PEEKXZHXSA-N 0.000 description 1
- CTOUBHACDYJELE-FRQOBSDTSA-N (4-methoxyphenyl)methyl (6R)-7-[[3-[(4-methoxyphenyl)methoxy]-3-oxo-2-phenylpropanoyl]amino]-3-methylidene-5,8-dioxo-5lambda4-thia-1-azabicyclo[4.2.0]octane-2-carboxylate Chemical compound C1=CC(OC)=CC=C1COC(=O)C(C=1C=CC=CC=1)C(=O)NC1C(=O)N2[C@@H]1S(=O)CC(=C)C2C(=O)OCC1=CC=C(OC)C=C1 CTOUBHACDYJELE-FRQOBSDTSA-N 0.000 description 1
- AHRPYRYWMZTAAB-WOWCSLBJSA-N (4-methoxyphenyl)methyl (6r)-3-methylidene-5,8-dioxo-7-[(2-phenylacetyl)amino]-5$l^{4}-thia-1-azabicyclo[4.2.0]octane-2-carboxylate Chemical compound C1=CC(OC)=CC=C1COC(=O)C1C(=C)CS(=O)[C@H]2N1C(=O)C2NC(=O)CC1=CC=CC=C1 AHRPYRYWMZTAAB-WOWCSLBJSA-N 0.000 description 1
- POBKSGRPIWDVBH-QETWGEEDSA-N (4-nitrophenyl)methyl (6R)-3-(acetyloxymethyl)-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2-carboxylate Chemical compound S1C(=CC=C1)CC(=O)NC1[C@@H]2N(C(C(=CS2)COC(C)=O)C(=O)OCC2=CC=C(C=C2)[N+](=O)[O-])C1=O POBKSGRPIWDVBH-QETWGEEDSA-N 0.000 description 1
- SURUJCRLPRUMAQ-JYPDZDFGSA-N (4-nitrophenyl)methyl (6R)-3-(butanoyloxymethyl)-7-[[2-(3-cyanophenyl)acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2-carboxylate Chemical compound C(#N)C=1C=C(C=CC=1)CC(=O)NC1[C@@H]2N(C(C(=CS2)COC(CCC)=O)C(=O)OCC2=CC=C(C=C2)[N+](=O)[O-])C1=O SURUJCRLPRUMAQ-JYPDZDFGSA-N 0.000 description 1
- SAOVTRPTSDMZBY-YVLIWWQVSA-N (4-nitrophenyl)methyl (6R)-3-methylidene-7-[[2-(4-nitrophenyl)acetyl]amino]-5,8-dioxo-5lambda4-thia-1-azabicyclo[4.2.0]octane-2-carboxylate Chemical compound C1=CC([N+](=O)[O-])=CC=C1COC(=O)C1C(=C)CS(=O)[C@H]2N1C(=O)C2NC(=O)CC1=CC=C([N+]([O-])=O)C=C1 SAOVTRPTSDMZBY-YVLIWWQVSA-N 0.000 description 1
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- RRYMAQUWDLIUPV-BXKDBHETSA-N cefacetrile Chemical compound S1CC(COC(=O)C)=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CC#N)[C@@H]12 RRYMAQUWDLIUPV-BXKDBHETSA-N 0.000 description 1
- 229960003972 cefacetrile Drugs 0.000 description 1
- FUBBGQLTSCSAON-PBFPGSCMSA-N cefaloglycin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)COC(=O)C)C(O)=O)=CC=CC=C1 FUBBGQLTSCSAON-PBFPGSCMSA-N 0.000 description 1
- 229950004030 cefaloglycin Drugs 0.000 description 1
- 229960000603 cefalotin Drugs 0.000 description 1
- 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 1
- 150000001782 cephems Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- HNEGQIOMVPPMNR-IHWYPQMZSA-N citraconic acid Chemical compound OC(=O)C(/C)=C\C(O)=O HNEGQIOMVPPMNR-IHWYPQMZSA-N 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- 125000003564 m-cyanobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(C#N)=C1[H])C([H])([H])* 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000006502 nitrobenzyl group Chemical group 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 229940056360 penicillin g Drugs 0.000 description 1
- 229940056367 penicillin v Drugs 0.000 description 1
- 150000002960 penicillins Chemical class 0.000 description 1
- XGISHOFUAFNYQF-UHFFFAOYSA-N pentanoyl chloride Chemical compound CCCCC(Cl)=O XGISHOFUAFNYQF-UHFFFAOYSA-N 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- WYCPNWWJYFGVMT-SLXFGWRHSA-N phenacyl (6R)-3-(acetyloxymethyl)-7-[(4-chlorobenzoyl)amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2-carboxylate Chemical compound ClC1=CC=C(C(=O)NC2[C@@H]3N(C(C(=CS3)COC(C)=O)C(=O)OCC(=O)C3=CC=CC=C3)C2=O)C=C1 WYCPNWWJYFGVMT-SLXFGWRHSA-N 0.000 description 1
- RGVFFXSJLIMEBT-FYHSTNQLSA-N phenacyl (6R)-7-[(4-chlorobenzoyl)amino]-3-methylidene-5,8-dioxo-5lambda4-thia-1-azabicyclo[4.2.0]octane-2-carboxylate Chemical compound C1=CC(Cl)=CC=C1C(=O)NC1C(=O)N2[C@@H]1S(=O)CC(=C)C2C(=O)OCC(=O)C1=CC=CC=C1 RGVFFXSJLIMEBT-FYHSTNQLSA-N 0.000 description 1
- BPLBGHOLXOTWMN-MBNYWOFBSA-N phenoxymethylpenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)COC1=CC=CC=C1 BPLBGHOLXOTWMN-MBNYWOFBSA-N 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- GJSNIIVUUXNCJN-GZNCHQMQSA-N propanoyloxymethyl (6R)-3-(acetyloxymethyl)-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2-carboxylate Chemical compound C1(=CC=CC=C1)CC(=O)NC1[C@@H]2N(C(C(=CS2)COC(C)=O)C(=O)OCOC(CC)=O)C1=O GJSNIIVUUXNCJN-GZNCHQMQSA-N 0.000 description 1
- FRXCINSCNDCQIY-GZNCHQMQSA-N propanoyloxymethyl (6R)-3-(acetyloxymethyl)-8-oxo-7-[[2-[4-(trifluoromethyl)phenyl]acetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2-carboxylate Chemical compound FC(C1=CC=C(C=C1)CC(=O)NC1[C@@H]2N(C(C(=CS2)COC(C)=O)C(=O)OCOC(CC)=O)C1=O)(F)F FRXCINSCNDCQIY-GZNCHQMQSA-N 0.000 description 1
- XCDHCWYUHUMICB-FCGLHUEYSA-N propanoyloxymethyl (6R)-3-methylidene-5,8-dioxo-7-[[2-[4-(trifluoromethyl)phenyl]acetyl]amino]-5lambda4-thia-1-azabicyclo[4.2.0]octane-2-carboxylate Chemical compound FC(C1=CC=C(C=C1)CC(=O)NC1[C@@H]2N(C(C(CS2=O)=C)C(=O)OCOC(CC)=O)C1=O)(F)F XCDHCWYUHUMICB-FCGLHUEYSA-N 0.000 description 1
- POZCAHUKTJHNIG-JNLOXFPDSA-N propanoyloxymethyl (6r)-3-methylidene-5,8-dioxo-7-[(2-phenylacetyl)amino]-5$l^{4}-thia-1-azabicyclo[4.2.0]octane-2-carboxylate Chemical compound C1([C@@H]2N(C1=O)C(C(CS2=O)=C)C(=O)OCOC(=O)CC)NC(=O)CC1=CC=CC=C1 POZCAHUKTJHNIG-JNLOXFPDSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- 125000006000 trichloroethyl group Chemical group 0.000 description 1
- 229940005605 valeric acid Drugs 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 229940102001 zinc bromide Drugs 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
- C07D501/02—Preparation
- C07D501/04—Preparation from compounds already containing the ring or condensed ring systems, e.g. by dehydrogenation of the ring, by introduction, elimination or modification of substituents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Cephalosporin Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/650,583 US4029651A (en) | 1976-01-19 | 1976-01-19 | Process for preparing 3-acyloxymethyl-2-cephem compounds |
| US05/650,585 US4031082A (en) | 1976-01-19 | 1976-01-19 | Process for preparing 3-acycloxymethyl-2-cephem compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE44133L IE44133L (en) | 1977-07-19 |
| IE44133B1 true IE44133B1 (en) | 1981-08-26 |
Family
ID=27095900
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE2598/76A IE44133B1 (en) | 1976-01-19 | 1976-11-26 | Process for preparing 2-cephem compounds |
Country Status (25)
-
1976
- 1976-11-26 IE IE2598/76A patent/IE44133B1/en unknown
- 1976-11-26 NZ NZ182737A patent/NZ182737A/xx unknown
- 1976-11-26 GR GR52271A patent/GR65892B/el unknown
- 1976-11-28 IL IL51021A patent/IL51021A/xx unknown
- 1976-12-03 AU AU20238/76A patent/AU503930B2/en not_active Expired
- 1976-12-10 DE DE2656144A patent/DE2656144C2/de not_active Expired
- 1976-12-22 BG BG034974A patent/BG30473A3/xx unknown
- 1976-12-23 PT PT66007A patent/PT66007B/pt unknown
-
1977
- 1977-01-04 SE SE7700077A patent/SE433849B/xx not_active IP Right Cessation
- 1977-01-10 MX MX775319U patent/MX3766E/es unknown
- 1977-01-10 CH CH24877A patent/CH628059A5/de not_active IP Right Cessation
- 1977-01-12 JP JP229877A patent/JPS5289698A/ja active Granted
- 1977-01-12 FR FR7700763A patent/FR2338280A1/fr active Granted
- 1977-01-13 YU YU00086/77A patent/YU8677A/xx unknown
- 1977-01-13 RO RO7789041A patent/RO69710A/ro unknown
- 1977-01-14 GB GB1450/77A patent/GB1566526A/en not_active Expired
- 1977-01-18 PL PL1977195386A patent/PL104370B1/pl not_active IP Right Cessation
- 1977-01-18 DK DK17977A patent/DK17977A/da not_active Application Discontinuation
- 1977-01-18 HU HU77EI723A patent/HU173592B/hu unknown
- 1977-01-18 NL NL7700500A patent/NL7700500A/xx not_active Application Discontinuation
- 1977-01-18 SU SU772439832A patent/SU703023A3/ru active
- 1977-01-19 DD DD7700197001A patent/DD128734A5/xx unknown
- 1977-01-19 AR AR266243A patent/AR213426A1/es active
- 1977-01-19 CS CS77368A patent/CS192474B2/cs unknown
- 1977-01-19 AT AT28177A patent/AT348121B/de not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| CH628059A5 (en) | 1982-02-15 |
| PL195386A1 (pl) | 1978-02-27 |
| AT348121B (de) | 1979-01-25 |
| DE2656144C2 (de) | 1985-08-29 |
| BG30473A3 (en) | 1981-06-15 |
| DE2656144A1 (de) | 1977-07-21 |
| MX3766E (es) | 1981-06-25 |
| IL51021A (en) | 1979-09-30 |
| JPS5289698A (en) | 1977-07-27 |
| PT66007A (en) | 1977-01-01 |
| FR2338280B1 (enrdf_load_stackoverflow) | 1979-09-28 |
| SU703023A3 (ru) | 1979-12-05 |
| FR2338280A1 (fr) | 1977-08-12 |
| SE7700077L (sv) | 1977-07-20 |
| NL7700500A (nl) | 1977-07-21 |
| JPS6120557B2 (enrdf_load_stackoverflow) | 1986-05-22 |
| IL51021A0 (en) | 1977-01-31 |
| IE44133L (en) | 1977-07-19 |
| AR213426A1 (es) | 1979-01-31 |
| PT66007B (en) | 1978-06-16 |
| AU2023876A (en) | 1978-06-08 |
| GB1566526A (en) | 1980-04-30 |
| DK17977A (da) | 1977-07-20 |
| NZ182737A (en) | 1978-04-28 |
| RO69710A (ro) | 1980-07-15 |
| SE433849B (sv) | 1984-06-18 |
| DD128734A5 (de) | 1977-12-07 |
| HU173592B (hu) | 1979-06-28 |
| AU503930B2 (en) | 1979-09-27 |
| ATA28177A (de) | 1978-06-15 |
| PL104370B1 (pl) | 1979-08-31 |
| YU8677A (en) | 1982-06-30 |
| GR65892B (enrdf_load_stackoverflow) | 1980-12-01 |
| CS192474B2 (en) | 1979-08-31 |
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