DD140454A5 - Verfahren zur herstellung von 3-eckige klammer auf 2-hydroxy-4-(substituierte)-phenyl eckige klammer zu cycloalkanone - Google Patents
Verfahren zur herstellung von 3-eckige klammer auf 2-hydroxy-4-(substituierte)-phenyl eckige klammer zu cycloalkanone Download PDFInfo
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- DD140454A5 DD140454A5 DD78207799A DD20779978A DD140454A5 DD 140454 A5 DD140454 A5 DD 140454A5 DD 78207799 A DD78207799 A DD 78207799A DD 20779978 A DD20779978 A DD 20779978A DD 140454 A5 DD140454 A5 DD 140454A5
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- German Democratic Republic
- Prior art keywords
- arh
- product
- compound
- methyl
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- -1 2-HYDROXY-4- (SUBSTITUTED) -PHENYL Chemical class 0.000 title claims abstract description 172
- 238000004519 manufacturing process Methods 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 159
- 238000000034 method Methods 0.000 claims abstract description 111
- 238000006243 chemical reaction Methods 0.000 claims abstract description 55
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 54
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims abstract description 52
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 28
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims abstract description 25
- 238000002360 preparation method Methods 0.000 claims abstract description 21
- 230000008569 process Effects 0.000 claims abstract description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 168
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 80
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 74
- 239000000047 product Substances 0.000 claims description 72
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 68
- 229910052739 hydrogen Inorganic materials 0.000 claims description 66
- 239000001257 hydrogen Substances 0.000 claims description 60
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 56
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 50
- 125000004432 carbon atom Chemical group C* 0.000 claims description 47
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 35
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 26
- 239000002904 solvent Substances 0.000 claims description 23
- 125000000217 alkyl group Chemical group 0.000 claims description 22
- 150000002431 hydrogen Chemical group 0.000 claims description 21
- 239000002253 acid Substances 0.000 claims description 19
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 19
- 238000003747 Grignard reaction Methods 0.000 claims description 18
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 18
- 125000006239 protecting group Chemical group 0.000 claims description 18
- 125000004043 oxo group Chemical group O=* 0.000 claims description 17
- 239000012442 inert solvent Substances 0.000 claims description 15
- 125000002947 alkylene group Chemical group 0.000 claims description 13
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 11
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical group CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
- 239000003638 chemical reducing agent Substances 0.000 claims description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- 239000012279 sodium borohydride Substances 0.000 claims description 8
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 8
- 239000007858 starting material Substances 0.000 claims description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 6
- 238000007239 Wittig reaction Methods 0.000 claims description 6
- 239000003054 catalyst Substances 0.000 claims description 6
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 238000005907 ketalization reaction Methods 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 125000004423 acyloxy group Chemical group 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 239000012024 dehydrating agents Substances 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 230000029936 alkylation Effects 0.000 claims description 3
- 238000005804 alkylation reaction Methods 0.000 claims description 3
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 3
- 230000003287 optical effect Effects 0.000 claims description 3
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 2
- 239000012448 Lithium borohydride Substances 0.000 claims description 2
- 238000010533 azeotropic distillation Methods 0.000 claims description 2
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims description 2
- 238000005984 hydrogenation reaction Methods 0.000 claims description 2
- XYDYWTJEGDZLTH-UHFFFAOYSA-N methylenetriphenylphosphorane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=C)C1=CC=CC=C1 XYDYWTJEGDZLTH-UHFFFAOYSA-N 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 238000007254 oxidation reaction Methods 0.000 claims description 2
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 2
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 2
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims 1
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 239000007795 chemical reaction product Substances 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 238000006567 deketalization reaction Methods 0.000 claims 1
- 239000004744 fabric Substances 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- NYEFUKPRSIREFK-UHFFFAOYSA-N lithium;dichloromethane Chemical compound [Li+].Cl[CH-]Cl NYEFUKPRSIREFK-UHFFFAOYSA-N 0.000 claims 1
- 229910052987 metal hydride Inorganic materials 0.000 claims 1
- 150000004681 metal hydrides Chemical class 0.000 claims 1
- JRTYPQGPARWINR-UHFFFAOYSA-N palladium platinum Chemical compound [Pd].[Pt] JRTYPQGPARWINR-UHFFFAOYSA-N 0.000 claims 1
- 229920000137 polyphosphoric acid Polymers 0.000 claims 1
- 229910052700 potassium Inorganic materials 0.000 claims 1
- 239000011591 potassium Substances 0.000 claims 1
- BBFCIBZLAVOLCF-UHFFFAOYSA-N pyridin-1-ium;bromide Chemical compound Br.C1=CC=NC=C1 BBFCIBZLAVOLCF-UHFFFAOYSA-N 0.000 claims 1
- 230000009466 transformation Effects 0.000 claims 1
- 238000000844 transformation Methods 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 abstract description 16
- 238000010992 reflux Methods 0.000 abstract description 12
- 239000000730 antalgic agent Substances 0.000 abstract description 10
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 abstract description 9
- 229940035676 analgesics Drugs 0.000 abstract description 7
- 230000001142 anti-diarrhea Effects 0.000 abstract description 5
- 239000001961 anticonvulsive agent Substances 0.000 abstract description 5
- 238000009835 boiling Methods 0.000 abstract description 5
- 239000000932 sedative agent Substances 0.000 abstract description 5
- 229940125681 anticonvulsant agent Drugs 0.000 abstract description 3
- 229940125723 sedative agent Drugs 0.000 abstract description 3
- DBGUUPDUZXSAJF-UHFFFAOYSA-N [Cu+].[I+] Chemical compound [Cu+].[I+] DBGUUPDUZXSAJF-UHFFFAOYSA-N 0.000 abstract description 2
- 229940125714 antidiarrheal agent Drugs 0.000 abstract description 2
- 239000003793 antidiarrheal agent Substances 0.000 abstract description 2
- 239000003204 tranquilizing agent Substances 0.000 abstract description 2
- 230000002936 tranquilizing effect Effects 0.000 abstract description 2
- KQVWOYAKDIRSQS-UHFFFAOYSA-N CCCCCCC(C)(C)C1=CC(=C(C=C1)C2CCCCC2=O)OCC3=CC=CC=C3 Chemical compound CCCCCCC(C)(C)C1=CC(=C(C=C1)C2CCCCC2=O)OCC3=CC=CC=C3 KQVWOYAKDIRSQS-UHFFFAOYSA-N 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 156
- 239000003921 oil Substances 0.000 description 129
- 235000019198 oils Nutrition 0.000 description 129
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 100
- 239000000203 mixture Substances 0.000 description 79
- 239000000243 solution Substances 0.000 description 73
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 72
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 60
- 239000011541 reaction mixture Substances 0.000 description 57
- 238000004458 analytical method Methods 0.000 description 53
- 238000002844 melting Methods 0.000 description 51
- 230000008018 melting Effects 0.000 description 51
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 42
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 37
- 239000000741 silica gel Substances 0.000 description 34
- 229910002027 silica gel Inorganic materials 0.000 description 34
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 32
- 229920002554 vinyl polymer Polymers 0.000 description 32
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 30
- 235000019341 magnesium sulphate Nutrition 0.000 description 30
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical class OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 29
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 25
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
- 238000012360 testing method Methods 0.000 description 24
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 23
- 239000003814 drug Substances 0.000 description 23
- 239000000376 reactant Substances 0.000 description 21
- 239000000284 extract Substances 0.000 description 20
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 description 20
- 238000004440 column chromatography Methods 0.000 description 18
- 229940079593 drug Drugs 0.000 description 18
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 17
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 17
- 238000011282 treatment Methods 0.000 description 16
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- FWFSEYBSWVRWGL-UHFFFAOYSA-N cyclohex-2-enone Chemical compound O=C1CCCC=C1 FWFSEYBSWVRWGL-UHFFFAOYSA-N 0.000 description 14
- DLLJVQNYBYOKGS-UHFFFAOYSA-N ethoxyethane;pentane Chemical compound CCCCC.CCOCC DLLJVQNYBYOKGS-UHFFFAOYSA-N 0.000 description 13
- 241000699670 Mus sp. Species 0.000 description 12
- 125000000753 cycloalkyl group Chemical group 0.000 description 12
- 239000012259 ether extract Substances 0.000 description 12
- 239000000706 filtrate Substances 0.000 description 12
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 12
- 241001465754 Metazoa Species 0.000 description 11
- 150000002148 esters Chemical class 0.000 description 11
- 238000006722 reduction reaction Methods 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- 239000000460 chlorine Substances 0.000 description 10
- 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 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- 230000009467 reduction Effects 0.000 description 10
- 150000003839 salts Chemical class 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 9
- 238000010828 elution Methods 0.000 description 9
- 150000002989 phenols Chemical class 0.000 description 9
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 8
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 8
- 241000699666 Mus <mouse, genus> Species 0.000 description 8
- 239000000543 intermediate Substances 0.000 description 8
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 7
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 7
- 239000005909 Kieselgur Substances 0.000 description 7
- 206010028347 Muscle twitching Diseases 0.000 description 7
- 241000700159 Rattus Species 0.000 description 7
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
- 229920002472 Starch Polymers 0.000 description 7
- 150000001299 aldehydes Chemical class 0.000 description 7
- 230000036461 convulsion Effects 0.000 description 7
- 150000002576 ketones Chemical class 0.000 description 7
- 230000004048 modification Effects 0.000 description 7
- 238000012986 modification Methods 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- 239000002002 slurry Substances 0.000 description 7
- 239000008107 starch Substances 0.000 description 7
- 235000019698 starch Nutrition 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- JZLCKKPJQXZUDI-UHFFFAOYSA-N 2-methyl-2-(3-phenylmethoxyphenyl)propanal Chemical compound O=CC(C)(C)C1=CC=CC(OCC=2C=CC=CC=2)=C1 JZLCKKPJQXZUDI-UHFFFAOYSA-N 0.000 description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 6
- 208000002193 Pain Diseases 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 230000000202 analgesic effect Effects 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 6
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- 230000008020 evaporation Effects 0.000 description 6
- 150000004795 grignard reagents Chemical class 0.000 description 6
- 239000012280 lithium aluminium hydride Substances 0.000 description 6
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
- 239000011777 magnesium Substances 0.000 description 6
- 229910052749 magnesium Inorganic materials 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
- 239000007818 Grignard reagent Substances 0.000 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 description 5
- 241000124008 Mammalia Species 0.000 description 5
- 229910019142 PO4 Inorganic materials 0.000 description 5
- 239000012298 atmosphere Substances 0.000 description 5
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 5
- 229910052794 bromium Inorganic materials 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 229940093499 ethyl acetate Drugs 0.000 description 5
- 235000019439 ethyl acetate Nutrition 0.000 description 5
- 239000005457 ice water Substances 0.000 description 5
- 229960005181 morphine Drugs 0.000 description 5
- 239000003208 petroleum Substances 0.000 description 5
- 239000010452 phosphate Substances 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- SGVYKUFIHHTIFL-UHFFFAOYSA-N 2-methylnonane Chemical compound CCCCCCCC(C)C SGVYKUFIHHTIFL-UHFFFAOYSA-N 0.000 description 4
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical class CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 206010010904 Convulsion Diseases 0.000 description 4
- 239000005977 Ethylene Substances 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- 150000001336 alkenes Chemical class 0.000 description 4
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 4
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- 239000004359 castor oil Substances 0.000 description 4
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
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- C07C37/001—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by modification in a side chain
- C07C37/002—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by modification in a side chain by transformation of a functional group, e.g. oxo, carboxyl
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- C07C37/01—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis
- C07C37/055—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis the substituted group being bound to oxygen, e.g. ether group
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- C07C37/01—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis
- C07C37/055—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis the substituted group being bound to oxygen, e.g. ether group
- C07C37/0555—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis the substituted group being bound to oxygen, e.g. ether group being esterified hydroxy groups
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- C07C39/12—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic with no unsaturation outside the aromatic rings
- C07C39/17—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic with no unsaturation outside the aromatic rings containing other rings in addition to the six-membered aromatic rings, e.g. cyclohexylphenol
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- C07C39/23—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic, containing six-membered aromatic rings and other rings, with unsaturation outside the aromatic rings
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- C07C39/24—Halogenated derivatives
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- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/26—Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of hydroxy or O-metal groups
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- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/48—Preparation of compounds having groups
- C07C41/50—Preparation of compounds having groups by reactions producing groups
- C07C41/56—Preparation of compounds having groups by reactions producing groups by condensation of aldehydes, paraformaldehyde, or ketones
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- C07C43/00—Ethers; Compounds having groups, groups or groups
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- C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
- C07C43/23—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing hydroxy or O-metal groups
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- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/95—Esters of quinone carboxylic acids
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
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- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Hematology (AREA)
- Psychiatry (AREA)
- Anesthesiology (AREA)
- Diabetes (AREA)
- Hospice & Palliative Care (AREA)
- Otolaryngology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyrane Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US83310277A | 1977-09-13 | 1977-09-13 |
Publications (1)
Publication Number | Publication Date |
---|---|
DD140454A5 true DD140454A5 (de) | 1980-03-05 |
Family
ID=25263433
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DD78218654A DD148631A5 (de) | 1977-09-13 | 1978-09-13 | Verfahren zur selektiven alkylierung eines 3-(2,4-dihydroxyphenyl)cycloalkanons |
DD78207799A DD140454A5 (de) | 1977-09-13 | 1978-09-13 | Verfahren zur herstellung von 3-eckige klammer auf 2-hydroxy-4-(substituierte)-phenyl eckige klammer zu cycloalkanone |
DD78218214A DD148334A5 (de) | 1977-09-13 | 1978-09-13 | Verfahren zur herstellung von substituierten cyclohexandionen-(1.3) |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DD78218654A DD148631A5 (de) | 1977-09-13 | 1978-09-13 | Verfahren zur selektiven alkylierung eines 3-(2,4-dihydroxyphenyl)cycloalkanons |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DD78218214A DD148334A5 (de) | 1977-09-13 | 1978-09-13 | Verfahren zur herstellung von substituierten cyclohexandionen-(1.3) |
Country Status (11)
Country | Link |
---|---|
JP (4) | JPS5538367A (hu) |
BE (1) | BE870404A (hu) |
CS (1) | CS216502B2 (hu) |
DD (3) | DD148631A5 (hu) |
HU (1) | HU181937B (hu) |
PL (5) | PL122834B1 (hu) |
PT (1) | PT68543A (hu) |
RO (5) | RO76721A (hu) |
SU (1) | SU991944A3 (hu) |
YU (1) | YU215478A (hu) |
ZA (1) | ZA785180B (hu) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1991015451A1 (en) * | 1990-04-05 | 1991-10-17 | Smithkline Beecham Pharma Gmbh | Novel derivatives of phenyl-cycloalkanes and -cycloalkenes |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4933475A (en) * | 1980-09-19 | 1990-06-12 | Pfizer, Inc. | Pharmacologically active 4-[2-hydroxy-4-(substituted)phenyl]naphthalen-2(1H)-ones and 2-ols, derivatives thereof and intermediates therefor |
US4331602A (en) | 1980-09-19 | 1982-05-25 | Pfizer Inc. | Pharmacologically active 4-[2-hydroxy-4-(substituted]phenyl)naphthalen-2(1H)-ones and 2-ols, derivatives thereof and intermediates therefor |
US4831059A (en) * | 1980-09-19 | 1989-05-16 | Pfizer Inc. | Producing analgesia with pharmacologically active 2-hydroxy-4-(substituted) phenyl cycloalkanes derivatives |
US4285867A (en) | 1980-09-19 | 1981-08-25 | Pfizer Inc. | Pharmacologically active 4-[2-hydroxy-4-(substituted)phenyl]naphthalen-2(1H)-ones and 2-ols, derivatives thereof and intermediates therefor |
US4835192A (en) * | 1980-09-19 | 1989-05-30 | Pfizer Inc. | Pharmacologically active 4-[2-hydroxy-4-(substituted)phenyl]naphthalen-2(1H)-ones and 2-ols, derivatives thereof and intermediates therefor |
US4486609A (en) * | 1981-03-16 | 1984-12-04 | Pfizer Inc. | Pharmacologically active 4-[2-hydroxy-4-(substituted)phenyl]naphthalen-2(1H)-ones and 2-ols, derivatives thereof and intermediates therefor |
US4921994A (en) * | 1980-09-19 | 1990-05-01 | Pfizer Inc. | Pharmacologically active 2-hydroxy-4-(substituted) phenyl cycloalkanes and derivatives thereof |
US4591225A (en) * | 1985-01-14 | 1986-05-27 | Molex Incorporated | Arrangement for interconnecting a printed circuit board with a multi-conductor cable |
WO2007127711A2 (en) * | 2006-04-24 | 2007-11-08 | Allergan, Inc. | Abnormal cannabidiols as agents for lowering intraocular pressure |
UA101004C2 (en) * | 2007-12-13 | 2013-02-25 | Теракос, Инк. | Derivatives of benzylphenylcyclohexane and use thereof |
-
1978
- 1978-09-12 PL PL1978227879A patent/PL122834B1/pl unknown
- 1978-09-12 HU HU78PI638A patent/HU181937B/hu unknown
- 1978-09-12 PT PT68543A patent/PT68543A/pt unknown
- 1978-09-12 BE BE190419A patent/BE870404A/xx not_active IP Right Cessation
- 1978-09-12 PL PL1978227878A patent/PL123771B1/pl unknown
- 1978-09-12 ZA ZA00785180A patent/ZA785180B/xx unknown
- 1978-09-12 PL PL1978227877A patent/PL122835B1/pl unknown
- 1978-09-12 YU YU02154/78A patent/YU215478A/xx unknown
- 1978-09-12 PL PL1978209554A patent/PL121079B1/pl unknown
- 1978-09-12 PL PL1978227876A patent/PL122765B1/pl unknown
- 1978-09-13 RO RO7899162A patent/RO76721A/ro unknown
- 1978-09-13 RO RO7898209A patent/RO77296A/ro unknown
- 1978-09-13 RO RO7898207A patent/RO77321A/ro unknown
- 1978-09-13 DD DD78218654A patent/DD148631A5/de unknown
- 1978-09-13 CS CS785911A patent/CS216502B2/cs unknown
- 1978-09-13 DD DD78207799A patent/DD140454A5/de unknown
- 1978-09-13 RO RO7898208A patent/RO77170A/ro unknown
- 1978-09-13 RO RO7898210A patent/RO77297A/ro unknown
- 1978-09-13 DD DD78218214A patent/DD148334A5/de unknown
- 1978-12-13 JP JP15404978A patent/JPS5538367A/ja active Granted
-
1980
- 1980-01-28 SU SU802875550A patent/SU991944A3/ru active
- 1980-06-26 JP JP55087229A patent/JPS5930693B2/ja not_active Expired
- 1980-06-26 JP JP55087227A patent/JPS605579B2/ja not_active Expired
- 1980-06-26 JP JP55087228A patent/JPS5930692B2/ja not_active Expired
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1991015451A1 (en) * | 1990-04-05 | 1991-10-17 | Smithkline Beecham Pharma Gmbh | Novel derivatives of phenyl-cycloalkanes and -cycloalkenes |
Also Published As
Publication number | Publication date |
---|---|
JPS5930692B2 (ja) | 1984-07-28 |
ZA785180B (en) | 1979-08-29 |
CS216502B2 (en) | 1982-11-26 |
RO77297A (ro) | 1981-06-22 |
RO77296A (ro) | 1981-06-22 |
JPS5639035A (en) | 1981-04-14 |
BE870404A (fr) | 1979-03-12 |
PL121079B1 (en) | 1982-04-30 |
PL209554A1 (pl) | 1979-06-04 |
JPS5639031A (en) | 1981-04-14 |
JPS605579B2 (ja) | 1985-02-12 |
RO77170A (ro) | 1981-06-22 |
PL122835B1 (en) | 1982-08-31 |
DD148334A5 (de) | 1981-05-20 |
RO77321A (ro) | 1981-08-17 |
PL122765B1 (en) | 1982-08-31 |
PL122834B1 (en) | 1982-08-31 |
SU991944A3 (ru) | 1983-01-23 |
HU181937B (en) | 1983-11-28 |
PL123771B1 (en) | 1982-11-30 |
JPS5538367A (en) | 1980-03-17 |
YU215478A (en) | 1983-06-30 |
JPS5930693B2 (ja) | 1984-07-28 |
JPS5639036A (en) | 1981-04-14 |
JPS5753352B2 (hu) | 1982-11-12 |
DD148631A5 (de) | 1981-06-03 |
PT68543A (en) | 1978-10-01 |
RO76721A (ro) | 1982-10-11 |
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