CA1041996A - Process for producing penicillins and cephalosporins - Google Patents

Process for producing penicillins and cephalosporins

Info

Publication number: CA1041996A
Authority: CA; Canada
Prior art keywords: acid; reacted; methyl; group; amino
Prior art date: 1971-04-15
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

CA139,833A

Other languages

English (en)

French (fr)

Other versions

CA139833S (en

Inventor

Shuntaro Takano

Toyoo Maeda

Yutaka Kodama

Toshiyasu Ishimaru

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.)

Toyama Chemical Co Ltd

Original Assignee

Toyama Chemical Co Ltd

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.)

1971-04-15

Filing date

1972-04-17

Publication date

1978-11-07

1971-04-15 Priority claimed from JP2414071A external-priority patent/JPS531278B1/ja

1971-04-15 Priority claimed from JP2414171A external-priority patent/JPS5231879B1/ja

1972-04-17 Application filed by Toyama Chemical Co Ltd filed Critical Toyama Chemical Co Ltd

1978-11-07 Application granted granted Critical

1978-11-07 Publication of CA1041996A publication Critical patent/CA1041996A/en

Status Expired legal-status Critical Current

Links

238000000034 method Methods 0.000 title claims abstract description 62
229930182555 Penicillin Natural products 0.000 title claims abstract description 17
229930186147 Cephalosporin Natural products 0.000 title claims abstract description 16
229940124587 cephalosporin Drugs 0.000 title claims abstract description 16
150000001780 cephalosporins Chemical class 0.000 title claims abstract description 16
150000002960 penicillins Chemical class 0.000 title claims abstract description 15
239000002253 acid Substances 0.000 claims abstract description 36
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 abstract description 29
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 abstract description 29
125000006239 protecting group Chemical group 0.000 claims abstract description 11
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 99
-1 amino, protected-amino Chemical group 0.000 claims description 45
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 44
JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical group CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 claims description 39
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 34
229940073584 methylene chloride Drugs 0.000 claims description 33
238000006243 chemical reaction Methods 0.000 claims description 23
125000000217 alkyl group Chemical group 0.000 claims description 18
125000003118 aryl group Chemical group 0.000 claims description 18
125000003545 alkoxy group Chemical group 0.000 claims description 17
125000004104 aryloxy group Chemical group 0.000 claims description 16
125000005843 halogen group Chemical group 0.000 claims description 16
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 15
125000003710 aryl alkyl group Chemical group 0.000 claims description 15
CJOGVHAUJHBLPB-UHFFFAOYSA-N 2-chloro-4-methyl-1,3,2-dioxaphospholane Chemical compound CC1COP(Cl)O1 CJOGVHAUJHBLPB-UHFFFAOYSA-N 0.000 claims description 12
125000002102 aryl alkyloxo group Chemical group 0.000 claims description 12
125000004663 dialkyl amino group Chemical group 0.000 claims description 12
125000001188 haloalkyl group Chemical group 0.000 claims description 12
159000000000 sodium salts Chemical class 0.000 claims description 12
239000011230 binding agent Substances 0.000 claims description 11
125000004438 haloalkoxy group Chemical group 0.000 claims description 11
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
229910052698 phosphorus Inorganic materials 0.000 claims description 10
239000011574 phosphorus Substances 0.000 claims description 10
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 claims description 10
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 9
150000003839 salts Chemical class 0.000 claims description 9
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 8
125000000623 heterocyclic group Chemical group 0.000 claims description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
239000001632 sodium acetate Substances 0.000 claims description 8
235000017281 sodium acetate Nutrition 0.000 claims description 8
NONJJLVGHLVQQM-JHXYUMNGSA-N phenethicillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C(C)OC1=CC=CC=C1 NONJJLVGHLVQQM-JHXYUMNGSA-N 0.000 claims description 7
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims description 7
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 claims description 6
NVIAYEIXYQCDAN-HWZXHQHMSA-N (6r)-7-amino-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound S1CC(C)=C(C(O)=O)N2C(=O)C(N)[C@@H]12 NVIAYEIXYQCDAN-HWZXHQHMSA-N 0.000 claims description 6
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 6
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
OLSFRDLMFAOSIA-UHFFFAOYSA-N 2-chloro-1,3,2-dioxaphospholane Chemical compound ClP1OCCO1 OLSFRDLMFAOSIA-UHFFFAOYSA-N 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
229910052783 alkali metal Inorganic materials 0.000 claims description 5
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 5
150000004682 monohydrates Chemical class 0.000 claims description 5
229960004894 pheneticillin Drugs 0.000 claims description 5
235000011056 potassium acetate Nutrition 0.000 claims description 5
229910052708 sodium Inorganic materials 0.000 claims description 5
239000011734 sodium Substances 0.000 claims description 5
XIURVHNZVLADCM-WPZCJLIBSA-N (6r)-3-(acetyloxymethyl)-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C1([C@@H]2N(C1=O)C(=C(CS2)COC(=O)C)C(O)=O)NC(=O)CC1=CC=CS1 XIURVHNZVLADCM-WPZCJLIBSA-N 0.000 claims description 4
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 4
125000004423 acyloxy group Chemical group 0.000 claims description 4
YFAGHNZHGGCZAX-JKIFEVAISA-N dicloxacillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C1=C(C)ON=C1C1=C(Cl)C=CC=C1Cl YFAGHNZHGGCZAX-JKIFEVAISA-N 0.000 claims description 4
229960003672 propicillin Drugs 0.000 claims description 4
IZQGELJKDARDMZ-UHFFFAOYSA-N 3-(2,6-dichlorophenyl)-5-methyl-1,2-oxazole-4-carbonyl chloride Chemical compound ClC(=O)C1=C(C)ON=C1C1=C(Cl)C=CC=C1Cl IZQGELJKDARDMZ-UHFFFAOYSA-N 0.000 claims description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 3
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 3
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
125000003282 alkyl amino group Chemical group 0.000 claims description 3
125000004414 alkyl thio group Chemical group 0.000 claims description 3
125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims description 3
125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 3
TXHWYSOQHNMOOU-UHFFFAOYSA-N chloro(diethoxy)phosphane Chemical compound CCOP(Cl)OCC TXHWYSOQHNMOOU-UHFFFAOYSA-N 0.000 claims description 3
NNPCWHQMEPPTJV-UHFFFAOYSA-N chloro(dimethoxy)phosphane Chemical compound COP(Cl)OC NNPCWHQMEPPTJV-UHFFFAOYSA-N 0.000 claims description 3
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
229940049954 penicillin Drugs 0.000 claims description 3
229910052700 potassium Inorganic materials 0.000 claims description 3
239000011591 potassium Substances 0.000 claims description 3
238000003797 solvolysis reaction Methods 0.000 claims description 3
MNANGXNDRCOVLE-UHFFFAOYSA-N 1,2-oxazole-4-carbonyl chloride Chemical compound ClC(=O)C=1C=NOC=1 MNANGXNDRCOVLE-UHFFFAOYSA-N 0.000 claims description 2
SHNXYKVYICSTHY-UHFFFAOYSA-N 2-chloro-1,3,2-dioxaphosphinane Chemical compound ClP1OCCCO1 SHNXYKVYICSTHY-UHFFFAOYSA-N 0.000 claims description 2
SMJRBWINMFUUDS-UHFFFAOYSA-N 2-thienylacetic acid Chemical compound OC(=O)CC1=CC=CS1 SMJRBWINMFUUDS-UHFFFAOYSA-N 0.000 claims description 2
AJYXPNIENRLELY-UHFFFAOYSA-N 2-thiophen-2-ylacetyl chloride Chemical compound ClC(=O)CC1=CC=CS1 AJYXPNIENRLELY-UHFFFAOYSA-N 0.000 claims description 2
WQXUUMUOERZZAE-UHFFFAOYSA-N 3-(2,6-dichlorophenyl)-5-methyl-1,2-oxazole-4-carboxylic acid Chemical compound OC(=O)C1=C(C)ON=C1C1=C(Cl)C=CC=C1Cl WQXUUMUOERZZAE-UHFFFAOYSA-N 0.000 claims description 2
PENHKTNQUJMHIR-UHFFFAOYSA-N 5-methyl-3-phenyl-1,2-oxazole-4-carboxylic acid Chemical compound OC(=O)C1=C(C)ON=C1C1=CC=CC=C1 PENHKTNQUJMHIR-UHFFFAOYSA-N 0.000 claims description 2
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 claims description 2
HSHGZXNAXBPPDL-HZGVNTEJSA-N 7beta-aminocephalosporanic acid Chemical compound S1CC(COC(=O)C)=C(C([O-])=O)N2C(=O)[C@@H]([NH3+])[C@@H]12 HSHGZXNAXBPPDL-HZGVNTEJSA-N 0.000 claims 6
125000002252 acyl group Chemical group 0.000 claims 4
229960004109 potassium acetate Drugs 0.000 claims 3
BDSSZTXPZHIYHM-UHFFFAOYSA-N 2-phenoxypropanoyl chloride Chemical compound ClC(=O)C(C)OC1=CC=CC=C1 BDSSZTXPZHIYHM-UHFFFAOYSA-N 0.000 claims 2
AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 claims 2
ZLVVDNKTHWEIOG-UHFFFAOYSA-N chloro(dimethyl)phosphane Chemical compound CP(C)Cl ZLVVDNKTHWEIOG-UHFFFAOYSA-N 0.000 claims 2
125000004093 cyano group Chemical group *C#N 0.000 claims 2
125000000753 cycloalkyl group Chemical group 0.000 claims 2
229940086542 triethylamine Drugs 0.000 claims 2
SXERGJJQSKIUIC-UHFFFAOYSA-N 2-Phenoxypropionic acid Chemical compound OC(=O)C(C)OC1=CC=CC=C1 SXERGJJQSKIUIC-UHFFFAOYSA-N 0.000 claims 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims 1
ZGUNAGUHMKGQNY-UHFFFAOYSA-N alpha-phenylglycine Chemical compound OC(=O)C(N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-UHFFFAOYSA-N 0.000 claims 1
125000004432 carbon atom Chemical group C* 0.000 claims 1
238000001816 cooling Methods 0.000 claims 1
HCSDJECSMANTCX-UHFFFAOYSA-N dichloro(methoxy)phosphane Chemical compound COP(Cl)Cl HCSDJECSMANTCX-UHFFFAOYSA-N 0.000 claims 1
150000004683 dihydrates Chemical class 0.000 claims 1
229910052739 hydrogen Inorganic materials 0.000 claims 1
239000001257 hydrogen Substances 0.000 claims 1
238000011065 in-situ storage Methods 0.000 claims 1
GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims 1
229960003975 potassium Drugs 0.000 claims 1
235000007686 potassium Nutrition 0.000 claims 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
239000000376 reactant Substances 0.000 claims 1
150000003018 phosphorus compounds Chemical class 0.000 abstract description 6
150000007513 acids Chemical class 0.000 abstract description 5
230000003115 biocidal effect Effects 0.000 abstract description 2
150000001735 carboxylic acids Chemical class 0.000 abstract description 2
239000000126 substance Substances 0.000 abstract description 2
239000000203 mixture Substances 0.000 description 44
239000013078 crystal Substances 0.000 description 43
239000000243 solution Substances 0.000 description 39
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 38
150000001875 compounds Chemical class 0.000 description 30
239000011541 reaction mixture Substances 0.000 description 20
239000000047 product Substances 0.000 description 15
239000010410 layer Substances 0.000 description 13
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
239000000706 filtrate Substances 0.000 description 8
238000000862 absorption spectrum Methods 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 6
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 6
239000012044 organic layer Substances 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
150000008065 acid anhydrides Chemical class 0.000 description 5
238000000354 decomposition reaction Methods 0.000 description 5
239000002904 solvent Substances 0.000 description 5
125000004665 trialkylsilyl group Chemical group 0.000 description 5
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
230000010933 acylation Effects 0.000 description 4
238000005917 acylation reaction Methods 0.000 description 4
125000005270 trialkylamine group Chemical group 0.000 description 4
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 3
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
150000001408 amides Chemical class 0.000 description 3
239000003125 aqueous solvent Substances 0.000 description 3
238000003776 cleavage reaction Methods 0.000 description 3
WOAZEKPXTXCPFZ-UHFFFAOYSA-N dimethyl(phenyl)azanium;chloride Chemical compound Cl.CN(C)C1=CC=CC=C1 WOAZEKPXTXCPFZ-UHFFFAOYSA-N 0.000 description 3
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 3
229940043265 methyl isobutyl ketone Drugs 0.000 description 3
230000002633 protecting effect Effects 0.000 description 3
230000007017 scission Effects 0.000 description 3
238000003756 stirring Methods 0.000 description 3
MBIZFBDREVRUHY-UHFFFAOYSA-N 2,6-Dimethoxybenzoic acid Chemical compound COC1=CC=CC(OC)=C1C(O)=O MBIZFBDREVRUHY-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
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
241000894006 Bacteria Species 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 2
125000003277 amino group Chemical group 0.000 description 2
150000008064 anhydrides Chemical class 0.000 description 2
230000000844 anti-bacterial effect Effects 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
MLIREBYILWEBDM-UHFFFAOYSA-N cyanoacetic acid Chemical compound OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 description 2
201000010099 disease Diseases 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
239000003814 drug Substances 0.000 description 2
150000002081 enamines Chemical class 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
235000019441 ethanol Nutrition 0.000 description 2
150000004820 halides Chemical class 0.000 description 2
FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 2
229960000443 hydrochloric acid Drugs 0.000 description 2
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
150000003017 phosphorus Chemical class 0.000 description 2
235000014786 phosphorus Nutrition 0.000 description 2
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
ZTQUIXWHQOHJAQ-MNWKQKBLSA-N (6R)-3-acetyloxy-4-methyl-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C(C)(=O)OC=1C(S[C@H]2N(C=1C(=O)O)C(C2NC(CC=1SC=CC=1)=O)=O)C ZTQUIXWHQOHJAQ-MNWKQKBLSA-N 0.000 description 1
MAUMSNABMVEOGP-UHFFFAOYSA-N (methyl-$l^{2}-azanyl)methane Chemical compound C[N]C MAUMSNABMVEOGP-UHFFFAOYSA-N 0.000 description 1
UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 description 1
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
ARAFEULRMHFMDE-UHFFFAOYSA-N 1,3-oxazolidine-2,5-dione Chemical compound O=C1CNC(=O)O1 ARAFEULRMHFMDE-UHFFFAOYSA-N 0.000 description 1
CVBUKMMMRLOKQR-UHFFFAOYSA-N 1-phenylbutane-1,3-dione Chemical compound CC(=O)CC(=O)C1=CC=CC=C1 CVBUKMMMRLOKQR-UHFFFAOYSA-N 0.000 description 1
BWRPEDIXOHZKFD-UHFFFAOYSA-N 2,2-diphenoxyacetic acid Chemical compound C=1C=CC=CC=1OC(C(=O)O)OC1=CC=CC=C1 BWRPEDIXOHZKFD-UHFFFAOYSA-N 0.000 description 1
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical class CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 1
VWVRASTUFJRTHW-UHFFFAOYSA-N 2-[3-(azetidin-3-yloxy)-4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound O=C(CN1C=C(C(OC2CNC2)=N1)C1=CN=C(NC2CC3=C(C2)C=CC=C3)N=C1)N1CCC2=C(C1)N=NN2 VWVRASTUFJRTHW-UHFFFAOYSA-N 0.000 description 1
QKSGIGXOKHZCQZ-UHFFFAOYSA-N 2-chloro-2-phenylacetic acid Chemical compound OC(=O)C(Cl)C1=CC=CC=C1 QKSGIGXOKHZCQZ-UHFFFAOYSA-N 0.000 description 1
WBJWXIQDBDZMAW-UHFFFAOYSA-N 2-hydroxynaphthalene-1-carbonyl chloride Chemical compound C1=CC=CC2=C(C(Cl)=O)C(O)=CC=C21 WBJWXIQDBDZMAW-UHFFFAOYSA-N 0.000 description 1
BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical class CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
PGUPJAPHYIEKLT-UHFFFAOYSA-N 2-pyridin-4-ylsulfanylacetic acid Chemical compound OC(=O)CSC1=CC=NC=C1 PGUPJAPHYIEKLT-UHFFFAOYSA-N 0.000 description 1
REIPZLFZMOQHJT-UHFFFAOYSA-N 3-(2-chloro-6-fluorophenyl)-5-methyl-1,2-oxazole-4-carboxylic acid Chemical compound OC(=O)C1=C(C)ON=C1C1=C(F)C=CC=C1Cl REIPZLFZMOQHJT-UHFFFAOYSA-N 0.000 description 1
UVEPOHNXGXVOJE-UHFFFAOYSA-N 3-(2-chlorophenyl)-5-methyl-1,2-oxazole-4-carboxylic acid Chemical compound OC(=O)C1=C(C)ON=C1C1=CC=CC=C1Cl UVEPOHNXGXVOJE-UHFFFAOYSA-N 0.000 description 1
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
WDJHALXBUFZDSR-UHFFFAOYSA-N Acetoacetic acid Natural products CC(=O)CC(O)=O WDJHALXBUFZDSR-UHFFFAOYSA-N 0.000 description 1
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 1
IVRMZWNICZWHMI-UHFFFAOYSA-N Azide Chemical compound [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 description 1
241000861718 Chloris <Aves> Species 0.000 description 1
XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
101100448208 Human herpesvirus 6B (strain Z29) U69 gene Proteins 0.000 description 1
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
JOOMLFKONHCLCJ-UHFFFAOYSA-N N-(trimethylsilyl)diethylamine Chemical compound CCN(CC)[Si](C)(C)C JOOMLFKONHCLCJ-UHFFFAOYSA-N 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
241000610375 Sparisoma viride Species 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 1
150000001242 acetic acid derivatives Chemical class 0.000 description 1
GCPWJFKTWGFEHH-UHFFFAOYSA-N acetoacetamide Chemical class CC(=O)CC(N)=O GCPWJFKTWGFEHH-UHFFFAOYSA-N 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
238000006136 alcoholysis reaction Methods 0.000 description 1
125000005910 alkyl carbonate group Chemical class 0.000 description 1
PYHXGXCGESYPCW-UHFFFAOYSA-N alpha-phenylbenzeneacetic acid Natural products C=1C=CC=CC=1C(C(=O)O)C1=CC=CC=C1 PYHXGXCGESYPCW-UHFFFAOYSA-N 0.000 description 1
RXDALBZNGVATNY-CWLIKTDRSA-N ampicillin trihydrate Chemical compound O.O.O.C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 RXDALBZNGVATNY-CWLIKTDRSA-N 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
150000001540 azides Chemical class 0.000 description 1
125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
229950005499 carbon tetrachloride Drugs 0.000 description 1
239000012295 chemical reaction liquid Substances 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
229960001701 chloroform Drugs 0.000 description 1
230000009850 completed effect Effects 0.000 description 1
HGBLNBBNRORJKI-WCABBAIRSA-N cyclacillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)C1(N)CCCCC1 HGBLNBBNRORJKI-WCABBAIRSA-N 0.000 description 1
229960004244 cyclacillin Drugs 0.000 description 1
150000001924 cycloalkanes Chemical class 0.000 description 1
150000005332 diethylamines Chemical class 0.000 description 1
125000005982 diphenylmethyl group Chemical group [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 1
238000000605 extraction Methods 0.000 description 1
238000001914 filtration Methods 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
238000002329 infrared spectrum Methods 0.000 description 1
235000015110 jellies Nutrition 0.000 description 1
239000008274 jelly Substances 0.000 description 1
229960002510 mandelic acid Drugs 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
229960005181 morphine Drugs 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
239000000843 powder Substances 0.000 description 1
238000007670 refining Methods 0.000 description 1
238000011160 research Methods 0.000 description 1
239000011369 resultant mixture Substances 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000013589 supplement Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
239000008096 xylene 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
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Cephalosporin Compounds (AREA)

CA139,833A 1971-04-15 1972-04-17 Process for producing penicillins and cephalosporins Expired CA1041996A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
JP2414071A JPS531278B1 (de)	1971-04-15	1971-04-15
JP2414171A JPS5231879B1 (de)	1971-04-15	1971-04-15

Publications (1)

Publication Number	Publication Date
CA1041996A true CA1041996A (en)	1978-11-07

Family

ID=26361623

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA139,833A Expired CA1041996A (en)	1971-04-15	1972-04-17	Process for producing penicillins and cephalosporins

Country Status (19)

Country	Link
AR (2)	AR201419A1 (de)
AT (1)	AT320849B (de)
BE (1)	BE781934A (de)
BR (1)	BR7202225D0 (de)
CA (1)	CA1041996A (de)
CH (1)	CH547309A (de)
CS (1)	CS178106B2 (de)
DD (1)	DD97422A5 (de)
DE (1)	DE2218209C3 (de)
DK (1)	DK142418B (de)
ES (1)	ES401525A1 (de)
FR (1)	FR2133686A1 (de)
HU (1)	HU166324B (de)
IE (1)	IE36288B1 (de)
IL (1)	IL39062A (de)
NL (1)	NL158803B (de)
NO (1)	NO146986C (de)
PH (1)	PH12645A (de)
SE (1)	SE392275C (de)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
BE791099A (fr) *	1971-11-09	1973-05-08	American Home Prod	Intermediaires pour la production de penicillines semi-synthetiques et procedes pour les obtenir
GB1459999A (en) *	1972-12-27	1976-12-31	Novo Industri As	Penicillin and cephalosporin intermediates
GB2161476B (en)	1984-05-25	1988-01-27	Toyama Chemical Co Ltd	2-aminothiazolyl-2-methoxyimino acetamides and their use in preparing cephalosporins

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
IE34822B1 (en) *	1969-12-26	1975-08-20	Univ Osaka	Process for producing 6-amino penicillanic acid

1972
- 1972-03-23 IL IL39062A patent/IL39062A/xx unknown
- 1972-03-29 SE SE7204191A patent/SE392275C/xx unknown
- 1972-04-06 ES ES401525A patent/ES401525A1/es not_active Expired
- 1972-04-11 BE BE781934A patent/BE781934A/xx not_active IP Right Cessation
- 1972-04-13 IE IE487/72A patent/IE36288B1/xx unknown
- 1972-04-13 FR FR7212995A patent/FR2133686A1/fr active Granted
- 1972-04-13 HU HUTO874A patent/HU166324B/hu unknown
- 1972-04-14 AT AT329272A patent/AT320849B/de not_active IP Right Cessation
- 1972-04-14 DD DD162300A patent/DD97422A5/xx unknown
- 1972-04-14 DE DE2218209A patent/DE2218209C3/de not_active Expired
- 1972-04-14 DK DK181972AA patent/DK142418B/da not_active IP Right Cessation
- 1972-04-14 CH CH553872A patent/CH547309A/fr not_active IP Right Cessation
- 1972-04-14 BR BR2225/72A patent/BR7202225D0/pt unknown
- 1972-04-14 NL NL7205083.A patent/NL158803B/xx not_active IP Right Cessation
- 1972-04-14 NO NO1299/72A patent/NO146986C/no unknown
- 1972-04-14 CS CS2553A patent/CS178106B2/cs unknown
- 1972-04-14 AR AR241483D patent/AR201419A1/es active
- 1972-04-17 PH PH13455A patent/PH12645A/en unknown
- 1972-04-17 CA CA139,833A patent/CA1041996A/en not_active Expired
1973
- 1973-01-01 AR AR246043A patent/AR204077A1/es active

Also Published As

Publication number	Publication date
NL7205083A (de)	1972-10-17
DE2218209A1 (de)	1972-10-26
AR204077A1 (es)	1975-11-20
DD97422A5 (de)	1973-05-05
BE781934A (fr)	1972-10-11
NL158803B (nl)	1978-12-15
BR7202225D0 (pt)	1973-07-17
ES401525A1 (es)	1975-09-01
NO146986B (no)	1982-10-04
FR2133686B1 (de)	1975-12-26
DE2218209C3 (de)	1980-10-16
IE36288B1 (en)	1976-09-29
IL39062A0 (en)	1972-05-30
DK142418C (de)	1982-12-06
DK142418B (da)	1980-10-27
IE36288L (en)	1972-10-15
NO146986C (no)	1983-01-12
DE2218209B2 (de)	1980-02-28
CS178106B2 (de)	1977-08-31
SE392275B (sv)	1977-03-21
SE392275C (sv)	1983-11-28
CH547309A (fr)	1974-03-29
AR201419A1 (es)	1975-03-14
FR2133686A1 (en)	1972-12-01
PH12645A (en)	1979-07-11
IL39062A (en)	1975-02-10
AT320849B (de)	1975-02-25
HU166324B (de)	1975-02-28

Publication	Publication Date	Title
CA1060454A (en)	1979-08-14	7-methoxycephalosporin derivatives
SE462097B (sv)	1990-05-07	Foerfarande foer framstaellning av en i huvudsak ren 6 beta-halogen penicillansyra
CA1041996A (en)	1978-11-07	Process for producing penicillins and cephalosporins
EP1068211A2 (de)	2001-01-17	Verfahren zur reinigung eines cephalosporin-derivats
EP0132394B1 (de)	1988-10-12	Herstellung von 3-Exomethylen-Cephalosporinen
EP0986565B1 (de)	2009-01-14	Verbessertes fällungsverfahren von 7-aminocephalosporansäure
US6448393B1 (en)	2002-09-10	Process for producing 3-cephem compounds
US3956287A (en)	1976-05-11	7-[(2-Oxo-1-pyridinyl)acylamino]cephalosporin derivatives
GB2095665A (en)	1982-10-06	Improved process for the preparation of penicillanic acid esters
EP0114750A2 (de)	1984-08-01	Antibakterielle beta-Lactam-Mittel
EP0030771B1 (de)	1983-04-13	Verfahren zur Herstellung von 6-Aminopenicillansäure-1,1-dioxid und seiner Salze
US4304909A (en)	1981-12-08	Process for producing 7-(D(-)-α-(4-ethyl-2,3-dioxo-1-piperazinecarboxamido)-α-(4-hydroxyphenyl)acetamido)-3-(5-(1-methyl-1,2,3,4-tetrazolyl)thiomethyl)-.DELTA.3 -cephem-4-carboxylic acid and a pharmaceutically acceptable salt thereof
CA1052770A (en)	1979-04-17	7-(D-.alpha.-HYDROXY-2-PHENYLACETAMIDO)-3-(THIOLATEDMETHYL)-3-CEPHEM-4-CARBOXYLIC ACIDS AND DERIVATIVES THEREOF
US3868364A (en)	1975-02-25	Improved process for producing penicillin compound
FI71562C (fi)	1987-01-19	Foerfarande foer framstaellning av 6- - substituerade penicillansyraderivat och saosom mellanprodukter anvaendbara 6-perfluoralkylsulfonyloxipenicillansyraderivat.
SE446985B (sv)	1986-10-20	Forfarande for framstellning av cefalosporinforeningar
EP0045717B1 (de)	1985-09-25	Cephalosporinderivate, ihre Herstellung und Anwendung
US4182868A (en)	1980-01-08	7-Methoxycephalosporin derivatives
GB2193213A (en)	1988-02-03	6-trifluoromethyl-1H-benzotriazol-1-yl diphenylphosphate and its use in preparing cephalosporin derivatives
US4173703A (en)	1979-11-06	Preparation of carbamates
JP4659959B2 (ja)	2011-03-30	３−セフェム化合物及びその製造法
US3946002A (en)	1976-03-23	Process for preparing cephalosporins
KR810000389B1 (ko)	1981-04-27	β-락탐계 항생물질 유도체의 제조방법
EP0115820B1 (de)	1988-12-21	Cephalosporinverbindungen und Verfahren zu ihrer Herstellung
KR850001960B1 (ko)	1985-12-31	세팔로스포린 유도체의 제조방법