CA1329210C - Procede pour la preparation de cis-1-carba(1-dethia)cephalosporines et de leurs intermediaires - Google Patents

Procede pour la preparation de cis-1-carba(1-dethia)cephalosporines et de leurs intermediaires

Info

Publication number: CA1329210C
Authority: CA; Canada
Prior art keywords: acid; formula; ester; phenyl; benzyl
Prior art date: 1985-07-17
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Fee Related

Application number

CA000616413A

Other languages

English (en)

Inventor

Eric Brian Sjogren

David Albert Evans

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.)

Harvard University

Original Assignee

Harvard University

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.)

1985-07-17

Filing date

1992-06-23

Publication date

1994-05-03

1985-07-17 Priority claimed from US06/755,982 external-priority patent/US4665171A/en

1992-06-23 Application filed by Harvard University filed Critical Harvard University

1992-06-23 Priority to CA000616413A priority Critical patent/CA1329210C/fr

1994-05-03 Application granted granted Critical

1994-05-03 Publication of CA1329210C publication Critical patent/CA1329210C/fr

2006-07-16 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

239000000543 intermediate Substances 0.000 title abstract description 20
229930186147 Cephalosporin Natural products 0.000 title description 5
229940124587 cephalosporin Drugs 0.000 title description 5
150000001780 cephalosporins Chemical class 0.000 title description 4
238000004519 manufacturing process Methods 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims abstract description 27
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 26
125000002541 furyl group Chemical group 0.000 claims abstract description 9
125000005036 alkoxyphenyl group Chemical group 0.000 claims abstract description 8
125000005037 alkyl phenyl group Chemical group 0.000 claims abstract description 7
125000005059 halophenyl group Chemical group 0.000 claims abstract description 7
125000001624 naphthyl group Chemical group 0.000 claims abstract description 6
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims abstract description 3
125000001544 thienyl group Chemical group 0.000 claims abstract description 3
125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims abstract 2
-1 trifluoroacetoxy Chemical group 0.000 claims description 62
125000001309 chloro group Chemical group Cl* 0.000 claims description 8
125000001246 bromo group Chemical group Br* 0.000 claims description 7
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical class O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 abstract description 54
150000002466 imines Chemical class 0.000 abstract description 26
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 abstract description 23
150000002148 esters Chemical class 0.000 abstract description 18
150000004820 halides Chemical class 0.000 abstract description 14
238000006352 cycloaddition reaction Methods 0.000 abstract description 13
230000015572 biosynthetic process Effects 0.000 abstract description 6
KJPRLNWUNMBNBZ-QPJJXVBHSA-N (E)-cinnamaldehyde Chemical compound O=C\C=C\C1=CC=CC=C1 KJPRLNWUNMBNBZ-QPJJXVBHSA-N 0.000 abstract description 4
229940117916 cinnamic aldehyde Drugs 0.000 abstract description 4
KJPRLNWUNMBNBZ-UHFFFAOYSA-N cinnamic aldehyde Natural products O=CC=CC1=CC=CC=C1 KJPRLNWUNMBNBZ-UHFFFAOYSA-N 0.000 abstract description 4
125000002950 monocyclic group Chemical group 0.000 abstract description 4
239000003782 beta lactam antibiotic agent Substances 0.000 abstract description 3
239000003242 anti bacterial agent Substances 0.000 abstract description 2
229940088710 antibiotic agent Drugs 0.000 abstract description 2
238000011914 asymmetric synthesis Methods 0.000 abstract description 2
238000003786 synthesis reaction Methods 0.000 abstract description 2
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 121
239000000243 solution Substances 0.000 description 41
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 39
239000000203 mixture Substances 0.000 description 39
239000002253 acid Substances 0.000 description 37
DKGAVHZHDRPRBM-UHFFFAOYSA-N tertiry butyl alcohol Natural products CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 37
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
238000000034 method Methods 0.000 description 27
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
238000006243 chemical reaction Methods 0.000 description 26
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 25
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
230000009467 reduction Effects 0.000 description 22
238000006722 reduction reaction Methods 0.000 description 22
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 21
239000002904 solvent Substances 0.000 description 21
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
125000000217 alkyl group Chemical group 0.000 description 19
239000000047 product Substances 0.000 description 19
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 17
229910052744 lithium Inorganic materials 0.000 description 17
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
229910021529 ammonia Inorganic materials 0.000 description 16
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 15
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 14
239000011541 reaction mixture Substances 0.000 description 14
238000002360 preparation method Methods 0.000 description 13
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 12
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
238000004587 chromatography analysis Methods 0.000 description 12
239000007787 solid Substances 0.000 description 12
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 11
230000000875 corresponding effect Effects 0.000 description 11
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 11
239000000377 silicon dioxide Substances 0.000 description 11
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
239000012442 inert solvent Substances 0.000 description 10
238000005949 ozonolysis reaction Methods 0.000 description 10
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 9
239000002585 base Substances 0.000 description 9
VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
125000006239 protecting group Chemical group 0.000 description 9
238000001953 recrystallisation Methods 0.000 description 9
238000007363 ring formation reaction Methods 0.000 description 9
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
239000012267 brine Substances 0.000 description 8
125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 description 8
229910052938 sodium sulfate Inorganic materials 0.000 description 8
235000011152 sodium sulphate Nutrition 0.000 description 8
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 7
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 7
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
150000008064 anhydrides Chemical class 0.000 description 7
125000001797 benzyl group Chemical class [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
230000003115 biocidal effect Effects 0.000 description 7
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 7
229960001701 chloroform Drugs 0.000 description 7
238000003756 stirring Methods 0.000 description 7
101150041968 CDC13 gene Proteins 0.000 description 6
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
125000002252 acyl group Chemical group 0.000 description 6
229910052786 argon Inorganic materials 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
150000001993 dienes Chemical class 0.000 description 6
125000004185 ester group Chemical group 0.000 description 6
235000019441 ethanol Nutrition 0.000 description 6
229910052736 halogen Inorganic materials 0.000 description 6
239000012044 organic layer Substances 0.000 description 6
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 6
VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 6
238000005809 transesterification reaction Methods 0.000 description 6
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 5
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 5
239000007832 Na2SO4 Substances 0.000 description 5
235000019445 benzyl alcohol Nutrition 0.000 description 5
238000010828 elution Methods 0.000 description 5
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 5
239000000284 extract Substances 0.000 description 5
150000002367 halogens Chemical class 0.000 description 5
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 5
229910052757 nitrogen Inorganic materials 0.000 description 5
229960005419 nitrogen Drugs 0.000 description 5
UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 description 4
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 4
GCBWDZYSLVSRRI-UHFFFAOYSA-N 3-aminoazetidin-2-one Chemical compound NC1CNC1=O GCBWDZYSLVSRRI-UHFFFAOYSA-N 0.000 description 4
HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 4
ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical compound OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 description 4
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 4
MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
CCGKOQOJPYTBIH-UHFFFAOYSA-N ethenone Chemical compound C=C=O CCGKOQOJPYTBIH-UHFFFAOYSA-N 0.000 description 4
238000010438 heat treatment Methods 0.000 description 4
229910052739 hydrogen Inorganic materials 0.000 description 4
239000001257 hydrogen Substances 0.000 description 4
239000003960 organic solvent Substances 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
YNWSXIWHOSSPCO-UHFFFAOYSA-N rhodium(2+) Chemical compound [Rh+2] YNWSXIWHOSSPCO-UHFFFAOYSA-N 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 4
BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 4
NDLIRBZKZSDGSO-UHFFFAOYSA-N tosyl azide Chemical compound CC1=CC=C(S(=O)(=O)[N-][N+]#N)C=C1 NDLIRBZKZSDGSO-UHFFFAOYSA-N 0.000 description 4
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 3
150000001266 acyl halides Chemical class 0.000 description 3
125000004442 acylamino group Chemical group 0.000 description 3
229910052783 alkali metal Inorganic materials 0.000 description 3
125000003545 alkoxy group Chemical group 0.000 description 3
125000005907 alkyl ester group Chemical group 0.000 description 3
150000001412 amines Chemical class 0.000 description 3
125000003277 amino group Chemical group 0.000 description 3
AQRHTGSVDQECPZ-UHFFFAOYSA-N azane;lithium Chemical compound [Li].N AQRHTGSVDQECPZ-UHFFFAOYSA-N 0.000 description 3
HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 3
150000003939 benzylamines Chemical class 0.000 description 3
150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
239000012141 concentrate Substances 0.000 description 3
239000002274 desiccant Substances 0.000 description 3
238000001035 drying Methods 0.000 description 3
239000000975 dye Substances 0.000 description 3
230000000694 effects Effects 0.000 description 3
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical class CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 3
PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
230000008020 evaporation Effects 0.000 description 3
238000000605 extraction Methods 0.000 description 3
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
230000006870 function Effects 0.000 description 3
150000004678 hydrides Chemical class 0.000 description 3
238000002955 isolation Methods 0.000 description 3
239000010410 layer Substances 0.000 description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
238000010992 reflux Methods 0.000 description 3
229920006395 saturated elastomer Polymers 0.000 description 3
239000011734 sodium Substances 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
239000012279 sodium borohydride Substances 0.000 description 3
229910000033 sodium borohydride Inorganic materials 0.000 description 3
239000011975 tartaric acid Substances 0.000 description 3
235000002906 tartaric acid Nutrition 0.000 description 3
CCSBNBKMACZDGN-UHFFFAOYSA-N (2-phenoxyacetyl) 2-phenoxyacetate Chemical compound C=1C=CC=CC=1OCC(=O)OC(=O)COC1=CC=CC=C1 CCSBNBKMACZDGN-UHFFFAOYSA-N 0.000 description 2
JTFLUJJESVAQGM-UHFFFAOYSA-N 1-aminoazetidin-2-one Chemical class NN1CCC1=O JTFLUJJESVAQGM-UHFFFAOYSA-N 0.000 description 2
IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 2
125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 description 2
WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
239000005695 Ammonium acetate Substances 0.000 description 2
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
241001024304 Mino Species 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
FHNINJWBTRXEBC-UHFFFAOYSA-N Sudan III Chemical compound OC1=CC=C2C=CC=CC2=C1N=NC(C=C1)=CC=C1N=NC1=CC=CC=C1 FHNINJWBTRXEBC-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
QQIRAVWVGBTHMJ-UHFFFAOYSA-N [dimethyl-(trimethylsilylamino)silyl]methane;lithium Chemical compound [Li].C[Si](C)(C)N[Si](C)(C)C QQIRAVWVGBTHMJ-UHFFFAOYSA-N 0.000 description 2
PIQKYIHZPBUFFS-UHFFFAOYSA-N acetic acid;1,3-oxazolidin-2-one Chemical compound CC(O)=O.O=C1NCCO1 PIQKYIHZPBUFFS-UHFFFAOYSA-N 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
230000010933 acylation Effects 0.000 description 2
238000005917 acylation reaction Methods 0.000 description 2
150000001299 aldehydes Chemical class 0.000 description 2
230000029936 alkylation Effects 0.000 description 2
238000005804 alkylation reaction Methods 0.000 description 2
235000019257 ammonium acetate Nutrition 0.000 description 2
229940043376 ammonium acetate Drugs 0.000 description 2
235000019270 ammonium chloride Nutrition 0.000 description 2
238000010533 azeotropic distillation Methods 0.000 description 2
WZPBZJONDBGPKJ-VEHQQRBSSA-N aztreonam Chemical class O=C1N(S([O-])(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(=N/OC(C)(C)C(O)=O)\C1=CSC([NH3+])=N1 WZPBZJONDBGPKJ-VEHQQRBSSA-N 0.000 description 2
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
229910000085 borane Inorganic materials 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
238000001816 cooling Methods 0.000 description 2
238000007257 deesterification reaction Methods 0.000 description 2
ZFTFAPZRGNKQPU-UHFFFAOYSA-N dicarbonic acid Chemical compound OC(=O)OC(O)=O ZFTFAPZRGNKQPU-UHFFFAOYSA-N 0.000 description 2
WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 2
238000007865 diluting Methods 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
238000001914 filtration Methods 0.000 description 2
239000011888 foil Substances 0.000 description 2
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UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 1
OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
239000002243 precursor Substances 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
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 description 1
239000001044 red dye Substances 0.000 description 1
229910052703 rhodium Inorganic materials 0.000 description 1
MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
ITDJKCJYYAQMRO-UHFFFAOYSA-L rhodium(2+);diacetate Chemical compound [Rh+2].CC([O-])=O.CC([O-])=O ITDJKCJYYAQMRO-UHFFFAOYSA-L 0.000 description 1
VUPQHSHTKBZVML-UHFFFAOYSA-J rhodium(3+);tetraacetate Chemical compound [Rh+3].[Rh+3].CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O VUPQHSHTKBZVML-UHFFFAOYSA-J 0.000 description 1
102200073741 rs121909602 Human genes 0.000 description 1
102220106802 rs139353014 Human genes 0.000 description 1
102220079670 rs759826252 Human genes 0.000 description 1
102220059961 rs786201335 Human genes 0.000 description 1
WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
229910000342 sodium bisulfate Inorganic materials 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
238000000638 solvent extraction Methods 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
125000005504 styryl group Chemical group 0.000 description 1
239000000126 substance Substances 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical compound [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
239000000725 suspension Substances 0.000 description 1
KUYMVWXKHQSIAS-UHFFFAOYSA-N tert-butyl 2-chloroacetate Chemical compound CC(C)(C)OC(=O)CCl KUYMVWXKHQSIAS-UHFFFAOYSA-N 0.000 description 1
NJMSEXDHKYVLKY-UHFFFAOYSA-N tert-butyl n-(2-oxoazetidin-3-yl)carbamate Chemical compound CC(C)(C)OC(=O)NC1CNC1=O NJMSEXDHKYVLKY-UHFFFAOYSA-N 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
150000007970 thio esters Chemical class 0.000 description 1
229910052719 titanium Inorganic materials 0.000 description 1
238000006257 total synthesis reaction Methods 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
PVFOMCVHYWHZJE-UHFFFAOYSA-N trichloroacetyl chloride Chemical compound ClC(=O)C(Cl)(Cl)Cl PVFOMCVHYWHZJE-UHFFFAOYSA-N 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
238000001665 trituration Methods 0.000 description 1
150000003738 xylenes Chemical class 0.000 description 1

Landscapes

Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

CA000616413A 1985-07-17 1992-06-23 Procede pour la preparation de cis-1-carba(1-dethia)cephalosporines et de leurs intermediaires Expired - Fee Related CA1329210C (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA000616413A CA1329210C (fr)	1985-07-17	1992-06-23	Procede pour la preparation de cis-1-carba(1-dethia)cephalosporines et de leurs intermediaires

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
US755,982		1985-05-17
US06/755,982 US4665171A (en)	1985-07-17	1985-07-17	Process and intermediates for β-lactam antibiotics
CA000513971A CA1310323C (fr)	1985-07-17	1986-07-16	Procede de preparation de cis carbo-1(dethio-1) cephalosporins et ses intermediaires
CA000616413A CA1329210C (fr)	1985-07-17	1992-06-23	Procede pour la preparation de cis-1-carba(1-dethia)cephalosporines et de leurs intermediaires

Related Parent Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000513971A Division CA1310323C (fr)	1985-07-17	1986-07-16	Procede de preparation de cis carbo-1(dethio-1) cephalosporins et ses intermediaires

Publications (1)

Publication Number	Publication Date
CA1329210C true CA1329210C (fr)	1994-05-03

Family

ID=25671050

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
CA000616413A Expired - Fee Related CA1329210C (fr)	1985-07-17	1992-06-23	Procede pour la preparation de cis-1-carba(1-dethia)cephalosporines et de leurs intermediaires
CA000616414A Expired - Fee Related CA1332059C (fr)	1985-07-17	1992-06-23	Procede pour la preparation de cis-1-carba(1-dethia)caphalosporines et de leurs intermediaires

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
CA000616414A Expired - Fee Related CA1332059C (fr)	1985-07-17	1992-06-23	Procede pour la preparation de cis-1-carba(1-dethia)caphalosporines et de leurs intermediaires

Country Status (1)

Country	Link
CA (2)	CA1329210C (fr)

1992
- 1992-06-23 CA CA000616413A patent/CA1329210C/fr not_active Expired - Fee Related
- 1992-06-23 CA CA000616414A patent/CA1332059C/fr not_active Expired - Fee Related

Also Published As

Publication number	Publication date
CA1332059C (fr)	1994-09-20

Legal Events

Date	Code	Title	Description
1998-05-04	MKLA	Lapsed

Publication	Publication Date	Title
CA1310323C (fr)	1992-11-17	Procede de preparation de cis carbo-1(dethio-1) cephalosporins et ses intermediaires
US4924012A (en)	1990-05-08	Process for preparing derivatives of baccatine III and of 10-deacetyl baccatine III
CA1262356A (fr)	1989-10-17	Ester de 1-carba (dethia) cephalosporine 3-triflate antibiotique
US5091525A (en)	1992-02-25	Monohydrate and DMF solvates of a new carbacephem antibiotic
DE69428403T2 (de)	2002-06-20	Verfahren zur Herstellung von Azetidinverbindungen und Ausgangsverbindungen dafür
KR100231223B1 (ko)	1999-11-15	아제티디논 화합물 및 이의 제조방법
CA1329210C (fr)	1994-05-03	Procede pour la preparation de cis-1-carba(1-dethia)cephalosporines et de leurs intermediaires
US4870169A (en)	1989-09-26	Intermediates for beta-lactam antibiotics
JPS6143357B2 (fr)	1986-09-26
KR910004090B1 (ko)	1991-06-22	β-락탐 화합물의 제조방법
US5637692A (en)	1997-06-10	Azetidinone intermediates to carbacephalosporins and process
CA1111856A (fr)	1981-11-03	Derives de l'azetidinone et leur preparation
CA1283924C (fr)	1991-05-07	(3s)-3-amino-2-oxo-4,4-dimethylazetidin-1-ylsulfate
US4734495A (en)	1988-03-29	Process and intermediates for beta-lactam antibiotics
US4775752A (en)	1988-10-04	Process and intermediates for beta-lactam antibiotics
JPH069553A (ja)	1994-01-18	１−［｜２ｓ｜−メチル−３−メルカプトプロピオニル−ピロリジン−｜２ｓ｜−カルボン酸の製法
HK1007140B (en)	1999-04-01	Process and intermediates for beta-lactam antibiotics
KR19980703584A (ko)	1998-11-05	살절지동물성 옥사디아진 중간체
KR900005322B1 (ko)	1990-07-27	β-락탐 항생물질 제조용 중간체
JPS5984861A (ja)	1984-05-16	アミノラクトンカルボン酸の製法
JP2000095780A (ja)	2000-04-04	カーバメート体類結晶の製造方法
EP0365190A1 (fr)	1990-04-25	Azétidinones comme intermédiaires pour carbacéphalosporines et procédé
JPH0797381A (ja)	1995-04-11	アゼチジノン化合物の新規な製法およびその新規原料化合物
EP1647552A1 (fr)	2006-04-19	Semisynthese de preparation de 10-deacetyl-n-debenzoyl-paclitaxel
JPH0147467B2 (fr)	1989-10-13