CA1098512A - Procede industriel d'obtention de derives d'enamine - Google Patents

Procede industriel d'obtention de derives d'enamine

Info

Publication number: CA1098512A
Authority: CA; Canada
Prior art keywords: phenyl; lower alkyl; group; amino; formula
Prior art date: 1975-02-20
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

CA344,631A

Other languages

English (en)

Inventor

Robert B. Woodward

Hans Bickel

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.)

Novartis AG

Original Assignee

Ciba Geigy Investments 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.)

1975-02-20

Filing date

1980-01-29

Publication date

1981-03-31

1975-02-20 Priority claimed from CH215775A external-priority patent/CH626091A5/de

1975-08-25 Priority claimed from CH1096275A external-priority patent/CH627759A5/de

1976-02-18 Priority claimed from CA246,040A external-priority patent/CA1080695A/fr

1980-01-29 Application filed by Ciba Geigy Investments Ltd filed Critical Ciba Geigy Investments Ltd

1980-01-29 Priority to CA344,631A priority Critical patent/CA1098512A/fr

1981-03-31 Application granted granted Critical

1981-03-31 Publication of CA1098512A publication Critical patent/CA1098512A/fr

Status Expired legal-status Critical Current

Links

238000000034 method Methods 0.000 title claims abstract description 16
238000004519 manufacturing process Methods 0.000 title claims abstract description 15
-1 amino, sulphoamino Chemical group 0.000 claims description 387
125000000217 alkyl group Chemical group 0.000 claims description 108
239000002253 acid Substances 0.000 claims description 82
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 58
125000003545 alkoxy group Chemical group 0.000 claims description 53
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 53
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 50
125000002252 acyl group Chemical group 0.000 claims description 46
125000003118 aryl group Chemical group 0.000 claims description 39
229910052739 hydrogen Inorganic materials 0.000 claims description 35
239000001257 hydrogen Substances 0.000 claims description 34
150000001875 compounds Chemical class 0.000 claims description 30
229910052736 halogen Inorganic materials 0.000 claims description 30
150000002367 halogens Chemical class 0.000 claims description 30
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 22
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 19
125000003277 amino group Chemical group 0.000 claims description 19
125000004432 carbon atom Chemical group C* 0.000 claims description 18
125000000753 cycloalkyl group Chemical group 0.000 claims description 17
150000002431 hydrogen Chemical group 0.000 claims description 16
125000004464 hydroxyphenyl group Chemical group 0.000 claims description 16
239000007858 starting material Substances 0.000 claims description 16
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 13
125000002541 furyl group Chemical group 0.000 claims description 12
125000005843 halogen group Chemical group 0.000 claims description 12
125000001544 thienyl group Chemical group 0.000 claims description 12
125000004414 alkyl thio group Chemical group 0.000 claims description 11
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
229910052757 nitrogen Inorganic materials 0.000 claims description 11
229910052760 oxygen Inorganic materials 0.000 claims description 11
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
229910052783 alkali metal Inorganic materials 0.000 claims description 9
125000003342 alkenyl group Chemical group 0.000 claims description 9
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 9
125000001624 naphthyl group Chemical group 0.000 claims description 9
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 8
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 8
238000006243 chemical reaction Methods 0.000 claims description 8
239000000126 substance Substances 0.000 claims description 8
229910052799 carbon Inorganic materials 0.000 claims description 7
125000001786 isothiazolyl group Chemical group 0.000 claims description 7
125000001424 substituent group Chemical group 0.000 claims description 7
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 6
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
125000004076 pyridyl group Chemical group 0.000 claims description 5
125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 5
125000003831 tetrazolyl group Chemical group 0.000 claims description 5
150000001340 alkali metals Chemical class 0.000 claims description 4
125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 4
125000005037 alkyl phenyl group Chemical group 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
125000001302 tertiary amino group Chemical group 0.000 claims description 4
125000004468 heterocyclylthio group Chemical group 0.000 claims description 3
125000002883 imidazolyl group Chemical group 0.000 claims description 3
239000012442 inert solvent Substances 0.000 claims description 3
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 3
JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 claims description 3
125000003441 thioacyl group Chemical group 0.000 claims description 3
125000004509 1,3,4-oxadiazol-2-yl group Chemical group O1C(=NN=C1)* 0.000 claims description 2
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
125000005108 alkenylthio group Chemical group 0.000 claims description 2
125000005185 naphthylcarbonyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 claims description 2
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
125000005400 pyridylcarbonyl group Chemical group N1=C(C=CC=C1)C(=O)* 0.000 claims description 2
125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims description 2
125000004521 1,3,4-thiadiazol-2-yl group Chemical group S1C(=NN=C1)* 0.000 claims 1
125000004149 thio group Chemical group *S* 0.000 claims 1
150000002148 esters Chemical class 0.000 abstract description 32
238000006798 ring closing metathesis reaction Methods 0.000 abstract 1
150000003254 radicals Chemical class 0.000 description 73
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 55
239000000243 solution Substances 0.000 description 40
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 38
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
239000000203 mixture Substances 0.000 description 36
150000003839 salts Chemical class 0.000 description 32
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
125000000623 heterocyclic group Chemical group 0.000 description 22
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 21
125000001931 aliphatic group Chemical group 0.000 description 21
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 21
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 21
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 19
229940073584 methylene chloride Drugs 0.000 description 19
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
239000000460 chlorine Substances 0.000 description 18
229910052801 chlorine Inorganic materials 0.000 description 18
239000000741 silica gel Substances 0.000 description 17
229910002027 silica gel Inorganic materials 0.000 description 17
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 16
239000004215 Carbon black (E152) Substances 0.000 description 15
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 15
230000000875 corresponding effect Effects 0.000 description 15
229930195733 hydrocarbon Natural products 0.000 description 15
125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 15
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 14
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
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 description 12
229910052708 sodium Inorganic materials 0.000 description 12
239000011734 sodium Substances 0.000 description 12
LDHQCZJRKDOVOX-UHFFFAOYSA-N trans-crotonic acid Natural products CC=CC(O)=O LDHQCZJRKDOVOX-UHFFFAOYSA-N 0.000 description 12
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 11
241001024304 Mino Species 0.000 description 11
125000004429 atom Chemical group 0.000 description 10
150000001732 carboxylic acid derivatives Chemical class 0.000 description 10
238000002844 melting Methods 0.000 description 10
230000008018 melting Effects 0.000 description 10
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 9
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
FZEVMBJWXHDLDB-ZCFIWIBFSA-N (6r)-5-thia-1-azabicyclo[4.2.0]oct-2-en-8-one Chemical class S1CC=CN2C(=O)C[C@H]21 FZEVMBJWXHDLDB-ZCFIWIBFSA-N 0.000 description 8
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 8
125000004423 acyloxy group Chemical group 0.000 description 8
239000000047 product Substances 0.000 description 8
229910052938 sodium sulfate Inorganic materials 0.000 description 8
235000011152 sodium sulphate Nutrition 0.000 description 8
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 7
229920006395 saturated elastomer Polymers 0.000 description 7
235000017557 sodium bicarbonate Nutrition 0.000 description 7
229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
229960001407 sodium bicarbonate Drugs 0.000 description 7
238000003756 stirring Methods 0.000 description 7
SXBDXXFTJVHSAF-ZCFIWIBFSA-N (6r)-5-thia-1-azabicyclo[4.2.0]oct-3-en-8-one Chemical class S1C=CCN2C(=O)C[C@H]21 SXBDXXFTJVHSAF-ZCFIWIBFSA-N 0.000 description 6
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 6
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 6
239000003795 chemical substances by application Substances 0.000 description 6
PYRZPBDTPRQYKG-UHFFFAOYSA-N cyclopentene-1-carboxylic acid Chemical compound OC(=O)C1=CCCC1 PYRZPBDTPRQYKG-UHFFFAOYSA-N 0.000 description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 6
238000002329 infrared spectrum Methods 0.000 description 6
239000000543 intermediate Substances 0.000 description 6
150000002500 ions Chemical class 0.000 description 6
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 6
239000011541 reaction mixture Substances 0.000 description 6
XJRIDJAGAYGJCK-UHFFFAOYSA-N (1-acetyl-5-bromoindol-3-yl) acetate Chemical compound C1=C(Br)C=C2C(OC(=O)C)=CN(C(C)=O)C2=C1 XJRIDJAGAYGJCK-UHFFFAOYSA-N 0.000 description 5
IKWLIQXIPRUIDU-ZCFIWIBFSA-N (6r)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical class OC(=O)C1=CCS[C@@H]2CC(=O)N12 IKWLIQXIPRUIDU-ZCFIWIBFSA-N 0.000 description 5
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
125000004442 acylamino group Chemical group 0.000 description 5
125000005236 alkanoylamino group Chemical group 0.000 description 5
125000004466 alkoxycarbonylamino group Chemical group 0.000 description 5
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
229910052794 bromium Inorganic materials 0.000 description 5
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 5
229910052751 metal Inorganic materials 0.000 description 5
239000002184 metal Substances 0.000 description 5
MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 5
125000002950 monocyclic group Chemical group 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
238000001228 spectrum Methods 0.000 description 5
239000000725 suspension Substances 0.000 description 5
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
239000005864 Sulphur Substances 0.000 description 4
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
125000002619 bicyclic group Chemical group 0.000 description 4
125000004122 cyclic group Chemical group 0.000 description 4
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 4
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 4
125000000524 functional group Chemical group 0.000 description 4
125000005842 heteroatom Chemical group 0.000 description 4
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 4
125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 description 4
239000007787 solid Substances 0.000 description 4
239000002904 solvent Substances 0.000 description 4
125000003396 thiol group Chemical group [H]S* 0.000 description 4
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 4
125000006016 2-bromoethoxy group Chemical group 0.000 description 3
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 3
FXJVNINSOKCNJP-UHFFFAOYSA-N 4-methylbenzenesulfinic acid Chemical compound CC1=CC=C(S(O)=O)C=C1 FXJVNINSOKCNJP-UHFFFAOYSA-N 0.000 description 3
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 3
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
101150034533 ATIC gene Proteins 0.000 description 3
241000894006 Bacteria Species 0.000 description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
VWQXZTFSQIIRQU-UHFFFAOYSA-N Cl.OC(=O)C1COCCO1 Chemical compound Cl.OC(=O)C1COCCO1 VWQXZTFSQIIRQU-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
LYAVXWPXKIFHBU-UHFFFAOYSA-N N-{2-[(1,2-diphenylhydrazinyl)carbonyl]-2-hydroxyhexanoyl}-6-aminohexanoic acid Chemical compound C=1C=CC=CC=1N(C(=O)C(O)(C(=O)NCCCCCC(O)=O)CCCC)NC1=CC=CC=C1 LYAVXWPXKIFHBU-UHFFFAOYSA-N 0.000 description 3
ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
150000001338 aliphatic hydrocarbons Chemical class 0.000 description 3
125000005194 alkoxycarbonyloxy group Chemical group 0.000 description 3
125000003282 alkyl amino group Chemical group 0.000 description 3
125000002947 alkylene group Chemical group 0.000 description 3
125000005237 alkyleneamino group Chemical group 0.000 description 3
125000001118 alkylidene group Chemical group 0.000 description 3
229910052786 argon Inorganic materials 0.000 description 3
125000004104 aryloxy group Chemical group 0.000 description 3
239000012298 atmosphere Substances 0.000 description 3
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
239000007795 chemical reaction product Substances 0.000 description 3
125000001309 chloro group Chemical group Cl* 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
LDHQCZJRKDOVOX-NSCUHMNNSA-N crotonic acid Chemical compound C\C=C\C(O)=O LDHQCZJRKDOVOX-NSCUHMNNSA-N 0.000 description 3
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
238000000354 decomposition reaction Methods 0.000 description 3
150000002081 enamines Chemical class 0.000 description 3
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 3
238000001914 filtration Methods 0.000 description 3
239000000499 gel Substances 0.000 description 3
150000002430 hydrocarbons Chemical class 0.000 description 3
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 3
239000011630 iodine Substances 0.000 description 3
229910052740 iodine Inorganic materials 0.000 description 3
LDHQCZJRKDOVOX-IHWYPQMZSA-N isocrotonic acid Chemical compound C\C=C/C(O)=O LDHQCZJRKDOVOX-IHWYPQMZSA-N 0.000 description 3
239000000463 material Substances 0.000 description 3
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
239000012299 nitrogen atmosphere Substances 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
239000001301 oxygen Substances 0.000 description 3
239000012071 phase Substances 0.000 description 3
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 3
BPLBGHOLXOTWMN-MBNYWOFBSA-N phenoxymethylpenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)COC1=CC=CC=C1 BPLBGHOLXOTWMN-MBNYWOFBSA-N 0.000 description 3
125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 3
125000006239 protecting group Chemical group 0.000 description 3
125000004469 siloxy group Chemical group [SiH3]O* 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
159000000000 sodium salts Chemical class 0.000 description 3
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
VDBJCDWTNCKRTF-UHFFFAOYSA-N 6'-hydroxyspiro[2-benzofuran-3,9'-9ah-xanthene]-1,3'-dione Chemical compound O1C(=O)C2=CC=CC=C2C21C1C=CC(=O)C=C1OC1=CC(O)=CC=C21 VDBJCDWTNCKRTF-UHFFFAOYSA-N 0.000 description 2
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IEJIGPNLZYLLBP-UHFFFAOYSA-N dimethyl carbonate Chemical group COC(=O)OC IEJIGPNLZYLLBP-UHFFFAOYSA-N 0.000 description 1
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
LIKFHECYJZWXFJ-UHFFFAOYSA-N dimethyldichlorosilane Chemical compound C[Si](C)(Cl)Cl LIKFHECYJZWXFJ-UHFFFAOYSA-N 0.000 description 1
238000004821 distillation Methods 0.000 description 1
238000010828 elution Methods 0.000 description 1
150000002084 enol ethers Chemical class 0.000 description 1
125000002587 enol group Chemical group 0.000 description 1
150000002085 enols Chemical class 0.000 description 1
125000004050 enoyl group Chemical group 0.000 description 1
239000012259 ether extract Substances 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
239000000284 extract Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
239000006260 foam Substances 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
150000008282 halocarbons Chemical class 0.000 description 1
125000001475 halogen functional group Chemical group 0.000 description 1
125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001145 hydrido group Chemical group *[H] 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 1
239000005457 ice water Substances 0.000 description 1
239000011261 inert gas Substances 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
239000013067 intermediate product Substances 0.000 description 1
125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
125000000654 isopropylidene group Chemical group C(C)(C)=* 0.000 description 1
125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
150000002596 lactones Chemical class 0.000 description 1
239000000155 melt Substances 0.000 description 1
HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
125000006626 methoxycarbonylamino group Chemical group 0.000 description 1
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
125000006606 n-butoxy group Chemical group 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000003506 n-propoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
125000006501 nitrophenyl group Chemical group 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
125000002801 octanoyl group Chemical group C(CCCCCCC)(=O)* 0.000 description 1
229940099990 ogen Drugs 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
239000003208 petroleum 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
ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
125000005544 phthalimido group Chemical group 0.000 description 1
125000005936 piperidyl group Chemical group 0.000 description 1
235000015497 potassium bicarbonate Nutrition 0.000 description 1
229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
239000011736 potassium bicarbonate Substances 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
238000002360 preparation method Methods 0.000 description 1
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
IOVGROKTTNBUGK-SJCJKPOMSA-N ritodrine Chemical compound N([C@@H](C)[C@H](O)C=1C=CC(O)=CC=1)CCC1=CC=C(O)C=C1 IOVGROKTTNBUGK-SJCJKPOMSA-N 0.000 description 1
229910052701 rubidium Inorganic materials 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
229910001961 silver nitrate Inorganic materials 0.000 description 1
125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
RZWQDAUIUBVCDD-UHFFFAOYSA-M sodium;benzenethiolate Chemical compound [Na+].[S-]C1=CC=CC=C1 RZWQDAUIUBVCDD-UHFFFAOYSA-M 0.000 description 1
125000000547 substituted alkyl group Chemical group 0.000 description 1
125000003107 substituted aryl group Chemical group 0.000 description 1
125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
HWCKGOZZJDHMNC-UHFFFAOYSA-M tetraethylammonium bromide Chemical compound [Br-].CC[N+](CC)(CC)CC HWCKGOZZJDHMNC-UHFFFAOYSA-M 0.000 description 1
125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
YUKQRDCYNOVPGJ-UHFFFAOYSA-N thioacetamide Chemical compound CC(N)=S YUKQRDCYNOVPGJ-UHFFFAOYSA-N 0.000 description 1
125000004568 thiomorpholinyl group Chemical group 0.000 description 1
230000017105 transposition Effects 0.000 description 1
125000005039 triarylmethyl group Chemical group 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
125000006007 trichloroethoxy group Chemical group 0.000 description 1
238000005406 washing Methods 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA344,631A 1975-02-20 1980-01-29 Procede industriel d'obtention de derives d'enamine Expired CA1098512A (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA344,631A CA1098512A (fr)	1975-02-20	1980-01-29	Procede industriel d'obtention de derives d'enamine

Applications Claiming Priority (6)

Application Number	Priority Date	Filing Date	Title
CH215775A CH626091A5 (en)	1975-02-20	1975-02-20	Process for preparing enol derivatives
CH2157/75		1975-02-20
CH10962/75		1975-08-25
CH1096275A CH627759A5 (en)	1975-08-25	1975-08-25	Process for preparing enol ether compounds
CA246,040A CA1080695A (fr)	1975-02-20	1976-02-18	Methode de fabrication de derives d'enols
CA344,631A CA1098512A (fr)	1975-02-20	1980-01-29	Procede industriel d'obtention de derives d'enamine

Publications (1)

Publication Number	Publication Date
CA1098512A true CA1098512A (fr)	1981-03-31

Family

ID=27425897

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA344,631A Expired CA1098512A (fr)	1975-02-20	1980-01-29	Procede industriel d'obtention de derives d'enamine

Country Status (1)

Country	Link
CA (1)	CA1098512A (fr)

1980
- 1980-01-29 CA CA344,631A patent/CA1098512A/fr not_active Expired

Legal Events

Date	Code	Title	Description
1998-03-31	MKEX	Expiry

Publication	Publication Date	Title
US4912224A (en)	1990-03-27	Carboxyalkenamidocephalosporins
FI56686C (fi)	1980-03-10	Foerfarande foer framstaellning av 7-aminocefalosporansyraderivat med antibiotisk verkan
CA1059988A (fr)	1979-08-07	Procede pour la fabrication de derives enol
CA1080695A (fr)	1980-07-01	Methode de fabrication de derives d'enols
US4024134A (en)	1977-05-17	Syn isomers of cephalosporins having α-hydroximino- or α-acyloxyiminoacylamido groups at position-7
CA1060432A (fr)	1979-08-14	DERIVES DE LA 7 .alpha. METOXYCEPHALOSPORINE
US3947413A (en)	1976-03-30	3-α-Substituted cephalosporins
US4074047A (en)	1978-02-14	7 2-(Aminocarbonylalkoxyimino)acetamido! derivatives of cephalosporin
EP0043546B1 (fr)	1986-01-29	7-Oxo-céphalosporines et 6-oxo-pénicillines, leurs homologues et procédé pour leur préparation
US4138555A (en)	1979-02-06	(6R,7R)-7-[2-aryl-2-(etherified oximino)acetamido]-3-carbamoyloxymethylceph-3-em-4-carboxylic acid 1-oxides
US4071529A (en)	1978-01-31	Derivatives of 6-aminopenicillanic acid
US4035359A (en)	1977-07-12	6α, β-Substituted penicillin derivatives
EP0000645B1 (fr)	1981-01-28	Isopénicillines, procédés pour leur préparation et compositions qui les contiennent
US4245107A (en)	1981-01-13	Cephalosporin derivatives and process for preparing the same
US4385177A (en)	1983-05-24	Cephalosporins having a carbamoylalkoxyiminoarylacetamido group at 7-position
CA1098512A (fr)	1981-03-31	Procede industriel d'obtention de derives d'enamine
US4154845A (en)	1979-05-15	Derivatives of 6-aminopenicillanic acid
US4086423A (en)	1978-04-25	Process for cephem synthesis
IE42318B1 (en)	1980-07-16	Improvements in or relating to cephalosporins
US4162360A (en)	1979-07-24	3-Carbamoyloxymethyl-7-substituted oximino acetamido cephalosporanic acid derivatives
PL103731B1 (pl)	1979-07-31	Sposob wytwarzania kwasu 6-metoksy-alfa-karboksypenicylanowego
US4137406A (en)	1979-01-30	Cephalosporins having a sulfur containing functional group in the 7-position side chain
CA1140554A (fr)	1983-02-01	Procede industriel d'obtention de derives de l'acide 2-(2-oxoazetidin-1-yl)-crotonique
CA1086739A (fr)	1980-09-30	Produits intermediaires contenant du mercure, utiles pour la preparation de 2-alkoxycephaloporines
CA1140555A (fr)	1983-02-01	Procede industriel d'obtention d'esters d'acide sulfonique et de composes d'acide 2-(2-oxoazetidin-1-yl)-hydroxycrotonique