CA1218055A - Preparation of 6-alpha-bromo- and/or 6,6-dibromo- penicillanic acid 1,1-dioxides - Google Patents
Preparation of 6-alpha-bromo- and/or 6,6-dibromo- penicillanic acid 1,1-dioxidesInfo
- Publication number
- CA1218055A CA1218055A CA000426045A CA426045A CA1218055A CA 1218055 A CA1218055 A CA 1218055A CA 000426045 A CA000426045 A CA 000426045A CA 426045 A CA426045 A CA 426045A CA 1218055 A CA1218055 A CA 1218055A
- Authority
- CA
- Canada
- Prior art keywords
- acid
- mmol
- dioxide
- hydrogen
- alkyl
- 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
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 29
- OSORMYZMWHVFOZ-UHFFFAOYSA-N phenethyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCCC1=CC=CC=C1 OSORMYZMWHVFOZ-UHFFFAOYSA-N 0.000 title claims abstract description 17
- 150000001875 compounds Chemical class 0.000 claims abstract description 63
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 374
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 301
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 181
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 126
- 229940093499 ethyl acetate Drugs 0.000 claims description 124
- 235000019439 ethyl acetate Nutrition 0.000 claims description 124
- 238000000034 method Methods 0.000 claims description 107
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 93
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 93
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 93
- 229910052794 bromium Inorganic materials 0.000 claims description 92
- 239000000047 product Substances 0.000 claims description 92
- 238000006243 chemical reaction Methods 0.000 claims description 83
- 230000008569 process Effects 0.000 claims description 78
- -1 alkyl cyano-acetate Chemical compound 0.000 claims description 71
- 239000002253 acid Substances 0.000 claims description 68
- 229910000042 hydrogen bromide Inorganic materials 0.000 claims description 62
- 239000000203 mixture Substances 0.000 claims description 61
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 57
- 125000000217 alkyl group Chemical group 0.000 claims description 51
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims description 50
- 239000012752 auxiliary agent Substances 0.000 claims description 43
- 239000001257 hydrogen Substances 0.000 claims description 41
- 229910052739 hydrogen Inorganic materials 0.000 claims description 41
- 239000002904 solvent Substances 0.000 claims description 39
- 150000003839 salts Chemical class 0.000 claims description 36
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 35
- 125000003118 aryl group Chemical group 0.000 claims description 32
- 239000007858 starting material Substances 0.000 claims description 32
- 238000005893 bromination reaction Methods 0.000 claims description 30
- 150000002148 esters Chemical class 0.000 claims description 30
- 239000003795 chemical substances by application Substances 0.000 claims description 29
- 239000003960 organic solvent Substances 0.000 claims description 29
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 28
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 claims description 27
- 235000010288 sodium nitrite Nutrition 0.000 claims description 25
- CSDTZUBPSYWZDX-UHFFFAOYSA-N n-pentyl nitrite Chemical compound CCCCCON=O CSDTZUBPSYWZDX-UHFFFAOYSA-N 0.000 claims description 24
- 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 claims description 21
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 21
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 20
- NGHVIOIJCVXTGV-UHFFFAOYSA-N 6beta-amino-penicillanic acid Natural products OC(=O)C1C(C)(C)SC2C(N)C(=O)N21 NGHVIOIJCVXTGV-UHFFFAOYSA-N 0.000 claims description 15
- 230000031709 bromination Effects 0.000 claims description 15
- 239000011541 reaction mixture Substances 0.000 claims description 15
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 235000011149 sulphuric acid Nutrition 0.000 claims description 14
- 229960002317 succinimide Drugs 0.000 claims description 13
- 239000001117 sulphuric acid Substances 0.000 claims description 13
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 12
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 10
- 125000005002 aryl methyl group Chemical group 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 9
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical class OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 9
- 150000003949 imides Chemical class 0.000 claims description 9
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 150000007524 organic acids Chemical class 0.000 claims description 9
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 claims description 9
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 8
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 8
- ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 claims description 8
- 229920006395 saturated elastomer Polymers 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 7
- CUONGYYJJVDODC-UHFFFAOYSA-N malononitrile Chemical compound N#CCC#N CUONGYYJJVDODC-UHFFFAOYSA-N 0.000 claims description 7
- 150000007522 mineralic acids Chemical class 0.000 claims description 7
- 239000000725 suspension Substances 0.000 claims description 7
- UXTFKIJKRJJXNV-UHFFFAOYSA-N 1-$l^{1}-oxidanylethanone Chemical group CC([O])=O UXTFKIJKRJJXNV-UHFFFAOYSA-N 0.000 claims description 6
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 6
- 229960001760 dimethyl sulfoxide Drugs 0.000 claims description 6
- 229940091173 hydantoin Drugs 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 230000009935 nitrosation Effects 0.000 claims description 6
- 238000007034 nitrosation reaction Methods 0.000 claims description 6
- 239000011734 sodium Substances 0.000 claims description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 5
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 claims description 5
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 5
- 239000005977 Ethylene Chemical group 0.000 claims description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 5
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 claims description 5
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 claims description 5
- 229910052708 sodium Inorganic materials 0.000 claims description 5
- 159000000000 sodium salts Chemical class 0.000 claims description 5
- 150000003512 tertiary amines Chemical class 0.000 claims description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- AVQQQNCBBIEMEU-UHFFFAOYSA-N 1,1,3,3-tetramethylurea Chemical compound CN(C)C(=O)N(C)C AVQQQNCBBIEMEU-UHFFFAOYSA-N 0.000 claims description 4
- XPFRXWCVYUEORT-UHFFFAOYSA-N Phenacemide Chemical compound NC(=O)NC(=O)CC1=CC=CC=C1 XPFRXWCVYUEORT-UHFFFAOYSA-N 0.000 claims description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
- 150000008049 diazo compounds Chemical class 0.000 claims description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 4
- 239000012634 fragment Substances 0.000 claims description 4
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 4
- PPCIUPZUHKICQG-UHFFFAOYSA-N pentan-2-yl nitrite Chemical compound CCCC(C)ON=O PPCIUPZUHKICQG-UHFFFAOYSA-N 0.000 claims description 4
- ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical class [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 claims description 4
- 125000001174 sulfone group Chemical group 0.000 claims description 4
- HHVIBTZHLRERCL-UHFFFAOYSA-N sulfonyldimethane Chemical compound CS(C)(=O)=O HHVIBTZHLRERCL-UHFFFAOYSA-N 0.000 claims description 4
- OSSNTDFYBPYIEC-UHFFFAOYSA-N 1-ethenylimidazole Chemical compound C=CN1C=CN=C1 OSSNTDFYBPYIEC-UHFFFAOYSA-N 0.000 claims description 3
- JJHHIJFTHRNPIK-UHFFFAOYSA-N Diphenyl sulfoxide Chemical compound C=1C=CC=CC=1S(=O)C1=CC=CC=C1 JJHHIJFTHRNPIK-UHFFFAOYSA-N 0.000 claims description 3
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 3
- 150000002357 guanidines Chemical class 0.000 claims description 3
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 claims description 3
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 claims description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
- LMYRWZFENFIFIT-UHFFFAOYSA-N toluene-4-sulfonamide Chemical compound CC1=CC=C(S(N)(=O)=O)C=C1 LMYRWZFENFIFIT-UHFFFAOYSA-N 0.000 claims description 3
- MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 claims description 2
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 2
- QQZWEECEMNQSTG-UHFFFAOYSA-N Ethyl nitrite Chemical compound CCON=O QQZWEECEMNQSTG-UHFFFAOYSA-N 0.000 claims description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 239000004305 biphenyl Substances 0.000 claims description 2
- 235000010290 biphenyl Nutrition 0.000 claims description 2
- 239000002131 composite material Substances 0.000 claims description 2
- 150000003951 lactams Chemical class 0.000 claims description 2
- 125000002950 monocyclic group Chemical group 0.000 claims description 2
- 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 claims description 2
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 claims description 2
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims 2
- 239000003085 diluting agent Substances 0.000 claims 2
- BEPAFCGSDWSTEL-UHFFFAOYSA-N dimethyl malonate Chemical compound COC(=O)CC(=O)OC BEPAFCGSDWSTEL-UHFFFAOYSA-N 0.000 claims 2
- 229910052751 metal Inorganic materials 0.000 claims 2
- 239000002184 metal Substances 0.000 claims 2
- ANGDWNBGPBMQHW-UHFFFAOYSA-N methyl cyanoacetate Chemical compound COC(=O)CC#N ANGDWNBGPBMQHW-UHFFFAOYSA-N 0.000 claims 2
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims 1
- AZFNGPAYDKGCRB-XCPIVNJJSA-M [(1s,2s)-2-amino-1,2-diphenylethyl]-(4-methylphenyl)sulfonylazanide;chlororuthenium(1+);1-methyl-4-propan-2-ylbenzene Chemical compound [Ru+]Cl.CC(C)C1=CC=C(C)C=C1.C1=CC(C)=CC=C1S(=O)(=O)[N-][C@@H](C=1C=CC=CC=1)[C@@H](N)C1=CC=CC=C1 AZFNGPAYDKGCRB-XCPIVNJJSA-M 0.000 claims 1
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims 1
- SZZYAOCSMNDGPI-UHFFFAOYSA-N methylsulfinylmethane;thiolane 1,1-dioxide Chemical compound CS(C)=O.O=S1(=O)CCCC1 SZZYAOCSMNDGPI-UHFFFAOYSA-N 0.000 claims 1
- 125000005633 phthalidyl group Chemical group 0.000 claims 1
- 235000010289 potassium nitrite Nutrition 0.000 claims 1
- 239000004304 potassium nitrite Substances 0.000 claims 1
- 239000000543 intermediate Substances 0.000 abstract description 14
- FKENQMMABCRJMK-RITPCOANSA-N sulbactam Chemical compound O=S1(=O)C(C)(C)[C@H](C(O)=O)N2C(=O)C[C@H]21 FKENQMMABCRJMK-RITPCOANSA-N 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 80
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 56
- WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 48
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 37
- 238000002474 experimental method Methods 0.000 description 32
- 238000003756 stirring Methods 0.000 description 32
- 238000001228 spectrum Methods 0.000 description 31
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 28
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 24
- 238000007792 addition Methods 0.000 description 23
- 238000004809 thin layer chromatography Methods 0.000 description 23
- 238000000605 extraction Methods 0.000 description 22
- 229960000819 sodium nitrite Drugs 0.000 description 22
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
- 239000007857 degradation product Substances 0.000 description 18
- 239000000284 extract Substances 0.000 description 18
- 239000010410 layer Substances 0.000 description 15
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 12
- 230000009102 absorption Effects 0.000 description 12
- 238000010521 absorption reaction Methods 0.000 description 12
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 12
- 238000005406 washing Methods 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
- 238000001816 cooling Methods 0.000 description 11
- 238000004090 dissolution Methods 0.000 description 11
- BBFCIBZLAVOLCF-UHFFFAOYSA-N pyridin-1-ium;bromide Chemical compound Br.C1=CC=NC=C1 BBFCIBZLAVOLCF-UHFFFAOYSA-N 0.000 description 11
- 235000010262 sodium metabisulphite Nutrition 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 10
- 238000001035 drying Methods 0.000 description 10
- 238000002955 isolation Methods 0.000 description 10
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 10
- 239000004296 sodium metabisulphite Substances 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- 235000019341 magnesium sulphate Nutrition 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 9
- 238000011282 treatment Methods 0.000 description 9
- JBKVHLHDHHXQEQ-UHFFFAOYSA-N epsilon-caprolactam Chemical compound O=C1CCCCCN1 JBKVHLHDHHXQEQ-UHFFFAOYSA-N 0.000 description 8
- RBKMMJSQKNKNEV-RITPCOANSA-N penicillanic acid Chemical compound OC(=O)[C@H]1C(C)(C)S[C@@H]2CC(=O)N21 RBKMMJSQKNKNEV-RITPCOANSA-N 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 8
- YIROYDNZEPTFOL-UHFFFAOYSA-N 5,5-Dimethylhydantoin Chemical compound CC1(C)NC(=O)NC1=O YIROYDNZEPTFOL-UHFFFAOYSA-N 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 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 7
- 239000007787 solid Substances 0.000 description 7
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 6
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- UWBHMRBRLOJJAA-UHFFFAOYSA-N oxaluric acid Chemical compound NC(=O)NC(=O)C(O)=O UWBHMRBRLOJJAA-UHFFFAOYSA-N 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- ORTFAQDWJHRMNX-UHFFFAOYSA-M oxidooxomethyl Chemical compound [O-][C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-M 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 150000002960 penicillins Chemical class 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- HCTVWSOKIJULET-LQDWTQKMSA-M phenoxymethylpenicillin potassium Chemical compound [K+].N([C@H]1[C@H]2SC([C@@H](N2C1=O)C([O-])=O)(C)C)C(=O)COC1=CC=CC=C1 HCTVWSOKIJULET-LQDWTQKMSA-M 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011833 salt mixture Substances 0.000 description 1
- 238000006748 scratching Methods 0.000 description 1
- 230000002393 scratching effect Effects 0.000 description 1
- 238000006884 silylation reaction Methods 0.000 description 1
- 239000004289 sodium hydrogen sulphite Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003021 water soluble solvent Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Communicable Diseases (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Cephalosporin Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Glass Compositions (AREA)
- Saccharide Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Steroid Compounds (AREA)
- Sink And Installation For Waste Water (AREA)
- Sewage (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8211301 | 1982-04-19 | ||
| GB8211301 | 1982-04-19 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1218055A true CA1218055A (en) | 1987-02-17 |
Family
ID=10529780
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000426045A Expired CA1218055A (en) | 1982-04-19 | 1983-04-18 | Preparation of 6-alpha-bromo- and/or 6,6-dibromo- penicillanic acid 1,1-dioxides |
| CA000426046A Expired CA1216842A (en) | 1982-04-19 | 1983-04-18 | Process for the preparation of penicillanic acid 1,1- dioxide and derivatives thereof |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000426046A Expired CA1216842A (en) | 1982-04-19 | 1983-04-18 | Process for the preparation of penicillanic acid 1,1- dioxide and derivatives thereof |
Country Status (14)
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4468351A (en) * | 1983-06-06 | 1984-08-28 | Pfizer Inc. | Process for debromination of dibromopenicillanic acid and derivatives |
| EP0139048A1 (en) * | 1983-10-18 | 1985-05-02 | Gist-Brocades N.V. | Process for the dehalogenation of 6,6-dibromopenicillanic acid 1,1-dioxide |
| EP0139047A1 (en) * | 1983-10-18 | 1985-05-02 | Gist-Brocades N.V. | Process for the preparation of 6,6-dibromopenicillanic acid 1,1-dioxide |
| US4760058A (en) * | 1984-08-29 | 1988-07-26 | Farmitalia Carlo Erba S.P.A. | Penam derivatives |
| US4816580A (en) * | 1986-04-10 | 1989-03-28 | Leo Pharmaceutical Products Ltd. A/S | Improved method for preparing penicillanic acid derivatives |
| JPS62249988A (ja) * | 1986-04-22 | 1987-10-30 | Taiho Yakuhin Kogyo Kk | ２β−ハロゲノメチル−２α−メチルペナム−３α−カルボン酸誘導体の製造法 |
| AR247212A1 (es) * | 1991-09-13 | 1994-11-30 | Bago Sa Labor | Procedimiento de preparacion de acido 1,1-dioxo penicilanico, sus sales y esteres. |
| ES2039299B1 (es) * | 1991-10-04 | 1994-05-16 | Asturpharma S A | Procedimiento de obtencion de esteres de acido 1,1-dioxopenicilanico y sus sales. |
| FR2706896B1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) * | 1993-06-23 | 1996-04-12 | Caillot Jean Luc | |
| DE69923535T2 (de) * | 1999-03-03 | 2006-01-05 | Astur Pharma S.A., Boadilla Del Monte | Verfahren zur Herstellung von Dioxopenicillansäurederivaten |
| CN101768035B (zh) * | 2009-01-05 | 2013-11-27 | 浙江华海药业股份有限公司 | 一种制备以及回收芳香甲基联苯化合物的方法 |
| CN104910184B (zh) * | 2015-04-27 | 2017-03-29 | 齐鲁天和惠世制药有限公司 | 一种6,6‑二溴青霉烷酸的制备方法 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4164497A (en) * | 1972-10-20 | 1979-08-14 | Fujisawa Pharmaceutical Co., Ltd. | 2-Substituted penam derivatives |
| IN149747B (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) * | 1977-06-07 | 1982-04-03 | Pfizer | |
| DK155942C (da) * | 1977-12-23 | 1989-10-23 | Pfizer | Analogifremgangsmaade til fremstilling af 6-aminopenicillansyre-1,1-dioxid og fysiologisk acceptable syreadditions- og basesalte deraf. |
| SE449103B (sv) * | 1979-03-05 | 1987-04-06 | Pfizer | Sett att framstella penicillansyra-1,1-dioxid samt estrar derav |
| US4432970A (en) * | 1979-11-23 | 1984-02-21 | Pfizer Inc. | 6-beta-Halopenicillanic acid 1,1-dioxides as beta-lactamase inhibitors |
| NL7908867A (nl) * | 1979-12-10 | 1981-07-01 | Gist Brocades Nv | Werkwijze voor het bereiden van 6-aminopenicillaanzuur- -1,1-dioxide en zijn zouten. |
| US4419284A (en) * | 1981-03-23 | 1983-12-06 | Pfizer Inc. | Preparation of halomethyl esters (and related esters) of penicillanic acid 1,1-dioxide |
| US4444687A (en) * | 1981-06-08 | 1984-04-24 | Bristol-Myers Company | 2β-Chloromethyl-2α-methylpenam-3α-carboxylic acid sulfone methylene diol mixed esters |
| US4360463A (en) * | 1981-09-02 | 1982-11-23 | Pfizer Inc. | Pure 6,6-diiodopenicillanic acid and process for its preparation |
-
1983
- 1983-04-08 PT PT76527A patent/PT76527B/pt not_active IP Right Cessation
- 1983-04-08 PT PT76526A patent/PT76526B/pt not_active IP Right Cessation
- 1983-04-13 ES ES521426A patent/ES8405019A1/es not_active Expired
- 1983-04-13 ES ES521425A patent/ES521425A0/es active Granted
- 1983-04-15 AT AT83200541T patent/ATE26982T1/de active
- 1983-04-15 DE DE8383200541T patent/DE3371338D1/de not_active Expired
- 1983-04-15 AT AT83200542T patent/ATE26447T1/de not_active IP Right Cessation
- 1983-04-15 EP EP83200541A patent/EP0093465B1/en not_active Expired
- 1983-04-15 EP EP83200542A patent/EP0092286B1/en not_active Expired
- 1983-04-15 DE DE8383200542T patent/DE3370799D1/de not_active Expired
- 1983-04-18 NO NO831358A patent/NO161565C/no unknown
- 1983-04-18 KR KR1019830001623A patent/KR870000310B1/ko not_active Expired
- 1983-04-18 GR GR71113A patent/GR77456B/el unknown
- 1983-04-18 KR KR1019830001624A patent/KR870000311B1/ko not_active Expired
- 1983-04-18 GR GR71112A patent/GR79249B/el unknown
- 1983-04-18 IE IE868/83A patent/IE54536B1/en not_active IP Right Cessation
- 1983-04-18 CA CA000426045A patent/CA1218055A/en not_active Expired
- 1983-04-18 FI FI831300A patent/FI80038C/fi not_active IP Right Cessation
- 1983-04-18 DK DK169183A patent/DK165295C/da not_active IP Right Cessation
- 1983-04-18 CA CA000426046A patent/CA1216842A/en not_active Expired
- 1983-04-18 IE IE869/83A patent/IE54522B1/en not_active IP Right Cessation
- 1983-04-18 FI FI831301A patent/FI78298C/fi not_active IP Right Cessation
- 1983-04-18 DK DK169083A patent/DK161891C/da active IP Right Grant
- 1983-04-18 NO NO831359A patent/NO159657C/no unknown
- 1983-04-19 US US06/486,981 patent/US4619786A/en not_active Expired - Fee Related
- 1983-04-19 US US06/486,403 patent/US4528135A/en not_active Expired - Fee Related
- 1983-04-19 JP JP58069076A patent/JPS58201788A/ja active Granted
- 1983-04-19 JP JP58069075A patent/JPS58201787A/ja active Granted
-
1984
- 1984-06-29 ES ES533883A patent/ES533883A0/es active Granted
-
1987
- 1987-05-29 JP JP62134809A patent/JPS6354376A/ja active Granted
-
1991
- 1991-11-04 DK DK181691A patent/DK165974C/da not_active IP Right Cessation
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Legal Events
| Date | Code | Title | Description |
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| MKEX | Expiry | ||
| MKEX | Expiry |
Effective date: 20040217 |