CH599182A5 - 3-Hydroxy-alkyl-4-carboxy-alkyl-phenol derivs. prepn. - Google Patents
3-Hydroxy-alkyl-4-carboxy-alkyl-phenol derivs. prepn.Info
- Publication number
- CH599182A5 CH599182A5 CH1125174A CH1125174A CH599182A5 CH 599182 A5 CH599182 A5 CH 599182A5 CH 1125174 A CH1125174 A CH 1125174A CH 1125174 A CH1125174 A CH 1125174A CH 599182 A5 CH599182 A5 CH 599182A5
- Authority
- CH
- Switzerland
- Prior art keywords
- formula
- compounds
- cooh
- alkyl
- radical
- Prior art date
Links
- -1 1H-tetrazol-5-yl Chemical group 0.000 claims abstract description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 7
- 150000003839 salts Chemical class 0.000 claims abstract description 5
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 4
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 4
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 3
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 3
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims abstract 2
- 150000001875 compounds Chemical class 0.000 claims description 32
- 238000002360 preparation method Methods 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- 239000000460 chlorine Substances 0.000 claims description 3
- 238000005661 deetherification reaction Methods 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 150000007529 inorganic bases Chemical class 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 150000007530 organic bases Chemical class 0.000 claims description 2
- 150000002989 phenols Chemical class 0.000 claims description 2
- 230000001939 inductive effect Effects 0.000 abstract description 3
- 241000124008 Mammalia Species 0.000 abstract description 2
- 206010000210 abortion Diseases 0.000 abstract description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 abstract 3
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 abstract 2
- 101100295738 Gallus gallus COR3 gene Proteins 0.000 abstract 1
- 230000017858 demethylation Effects 0.000 abstract 1
- 238000010520 demethylation reaction Methods 0.000 abstract 1
- 150000002170 ethers Chemical class 0.000 abstract 1
- 230000001077 hypotensive effect Effects 0.000 abstract 1
- 230000005906 menstruation Effects 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 239000007858 starting material Substances 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 239000000203 mixture Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 229960000583 acetic acid Drugs 0.000 description 6
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 239000008096 xylene Substances 0.000 description 3
- MNALUTYMBUBKNX-UHFFFAOYSA-N 6-methoxy-3,4-dihydro-2h-naphthalen-1-one Chemical compound O=C1CCCC2=CC(OC)=CC=C21 MNALUTYMBUBKNX-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- CMSYDJVRTHCWFP-UHFFFAOYSA-N triphenylphosphane;hydrobromide Chemical compound Br.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 CMSYDJVRTHCWFP-UHFFFAOYSA-N 0.000 description 2
- 210000004291 uterus Anatomy 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- YZWKKMVJZFACSU-UHFFFAOYSA-N 1-bromopentane Chemical compound CCCCCBr YZWKKMVJZFACSU-UHFFFAOYSA-N 0.000 description 1
- DMSOFGPGHKQYMB-UHFFFAOYSA-N 4-ethyl-7-methoxy-1,2-dihydronaphthalene Chemical compound COC1=CC=C2C(CC)=CCCC2=C1 DMSOFGPGHKQYMB-UHFFFAOYSA-N 0.000 description 1
- NTJPVVKEZMOHNU-UHFFFAOYSA-N 6-(oxan-4-yl)-1h-indazole Chemical compound C1COCCC1C1=CC=C(C=NN2)C2=C1 NTJPVVKEZMOHNU-UHFFFAOYSA-N 0.000 description 1
- IASRMNRQZIRYHM-UHFFFAOYSA-N 6-carboxyhexyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCCCCCC(=O)O)C1=CC=CC=C1 IASRMNRQZIRYHM-UHFFFAOYSA-N 0.000 description 1
- KBFHIQNXUXKWGO-UHFFFAOYSA-N 6-methoxy-2-pentyl-3,4-dihydro-2h-naphthalen-1-one Chemical compound COC1=CC=C2C(=O)C(CCCCC)CCC2=C1 KBFHIQNXUXKWGO-UHFFFAOYSA-N 0.000 description 1
- GWWJRIYTDDYEHJ-UHFFFAOYSA-N 7-methoxy-3-pentyl-1,2-dihydronaphthalene Chemical compound C1=C(OC)C=C2CCC(CCCCC)=CC2=C1 GWWJRIYTDDYEHJ-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- QZGVFZFUAUEYFS-UHFFFAOYSA-N COC(C=C1CCC2CCC(C=C3)=CC=C3F)=CC=C1C2=O Chemical compound COC(C=C1CCC2CCC(C=C3)=CC=C3F)=CC=C1C2=O QZGVFZFUAUEYFS-UHFFFAOYSA-N 0.000 description 1
- 208000007530 Essential hypertension Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 231100000176 abortion Toxicity 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000007171 acid catalysis Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000035606 childbirth Effects 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- OVEHNNQXLPJPPL-UHFFFAOYSA-N lithium;n-propan-2-ylpropan-2-amine Chemical compound [Li].CC(C)NC(C)C OVEHNNQXLPJPPL-UHFFFAOYSA-N 0.000 description 1
- 210000004914 menses Anatomy 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 1
- 235000019321 monosodium tartrate Nutrition 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000004714 phosphonium salts Chemical class 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229940119126 sodium bitartrate Drugs 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000003191 uterotonic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/64—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of functional groups containing oxygen only in singly bound form
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/40—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with ozone; by ozonolysis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/42—Unsaturated compounds containing hydroxy or O-metal groups
- C07C59/52—Unsaturated compounds containing hydroxy or O-metal groups a hydroxy or O-metal group being bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/42—Unsaturated compounds containing hydroxy or O-metal groups
- C07C59/56—Unsaturated compounds containing hydroxy or O-metal groups containing halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
- C07C59/64—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Prodn. of new phenol derivs. of formula (I):- comprises demethylation of the corresp. ethers (I: HO- is CH3O-) then opt. converting (I) (where X'=COOH), to a salt with.Cpds. with X' =COOH can also be esterified to give cpds. with X=COR3 (R3=alkoxy), or converted to quaternary ammonium salts. In the formula, R1 is H or CH3. R2 is 5-8C alkyl or -(CH2)2-p-C6H4-Z. Z is H, F or Cl. m is 5 or 6. X' is COOH or 1H-tetrazol-5-yl.(I) have uterus-stimulating (abortion-, labour- or menstruation-inducing) and hypotensive activities. The usual dose for large mammals is 10-500 mg/day. (I) is e.g. d, 1-4-(6'-carboxyhexyl)-3-(3'-hydroxyoctyl)phenol.
Description
Die Erfindung betrifft ein Verfahren zur Herstellung von neuen Phenolderivaten der Formel I (siehe Formelblatt), worin R1 für Wasserstoff oder Methyl, R2 für Alkyl mit 5 bis 8 Kohlenstoffatomen oder für den Rest
EMI1.1
steht, wobei Z den Rest Wasserstoff, Fluor oder Chlor darstellt, m die Zahl 5 oder 6 und X die Reste
EMI1.2
oder -CORs bedeuten, wobei Rs Hydroxy, niederes Alkoxy oder die Aminogruppe darstellt.
Die Verbindungen der Formel I, worin X den Rest -COOH bedeutet, können in pharmakologisch akzeptable Salze übergeführt werden. Pharmakologisch akzeptable Salze sind solche mit pharmakologisch akzeptablen Metallkationen, Ammonium- und Aminkationen oder quaternären Ammoniumkationen.
Erfindungsgemäss gelangt man zu Verbindungen der Formel I, indem man Verbindungen der Formel II, worin R1, R2 und m obige Bedeutung besitzen und X' die Reste
EMI1.3
oder -COOH bedeutet, der Ätherspaltung unterwirft und a) gegebenenfalls im Falle der Herstellung von Verbindungen der Formel I, worin X den Rest -COR3 bedeutet, wobei R3 niederes Alkoxy oder die Aminogruppe darstellt, Verbindungen der Formel I', worin Rt, R2 und m obige Bedeutung besitzen und X' den Rest -COOH bedeutet, nach an sich bekannten Methoden verestert oder in die Amidgruppe überführt, oder b) gegebenenfalls im Falle der Herstellung von pharmazeutisch akzeptablen Salzen von Verbindungen der Formel I, worin X den Rest -COOH bedeutet, Verbindungen der Formel I', worin R1, R2, m und X' obige Bedeutung haben,
mit anorganischen oder organischen Basen behandelt
Die Ätherspaltung erfolgt nach an sich bekannten Methoden, beispielsweise mit einem Bortrihalogenid, vorzugsweise Bortribromid, oder Halogenwasserstoff, vorzugsweise Bromwasserstoff, in einem unter den Reaktionsbedingungen inerten Lösungsmittel, wie z. B. Methylenchlorid oder Chloroform bei Temperaturen von - 700 und + 200.
Die als Ausgangsmaterial verwendeten Verbindungen der Formel II werden hergestellt, indem man 6-Methoxy-ltetralon (Formel III) mit einer Verbindung der Formel IV, worin R2 obige Bedeutung besitzt und A für Jod, Brom, Chlor, -O-Tosyl oder O-Mesyl steht, umsetzt. Hierbei wird zuerst mit Cyclohexylamin in siedendem Xylol das Imid hergestellt, letzteres wird in Tetrahydrofuran zuerst mit Lithiumdiisopropylamid, dann mit 1,0 bis 1,3 Mol einer Verbindung der Formel IV umgesetzt und das entstandene Produkt mit wässriger Essigsäure hydrolysiert, wobei eine Verbindung der Formel V entsteht. Letzteres wird mit einem komplexen Hydrid, vorzugsweise mit Natriumborhydrid in MethylenchloridlÄthanol bei Temperaturen von 0 bis 600 C reduziert, wobei eine Verbindung der Formel Vl entsteht.
Letzteres wird unter saurer Katalyse zu Verbindungen der Formel VII umgesetzt. Besonders eignet sich die Anwendung katalytischer Mengen von Triphenylphosphinhydrobromid in einer Lösung von Methylenchlorid bei Temperaturen zwischen 0 und 280 C. Die Verbindungen der Formel VII werden hierauf einer Ozonspaltung unterworfen. Hierzu werden sie in einer Lösung von Methylenchlorid bei Temperaturen von -80 bis - 600 C mit ozonhaltigen (1-7 /o) Sauerstoff behandelt, bis 1 Mol Ozon aufgenommen ist. Nachher wird Zink und Essigsäure zugegeben, das Gemisch unter Rühren auf 250 C gebracht, wobei Verbindungen der Formel VIII entstehen.
Letztere werden im Falle der Herstellung von Verbindungen der Formel IX' bei einer Temperatur von -80 und - 150 C in Diglym, Tetrahydrofuran oder Äther als Lösungsmittel mit 1 Mol Lithium-tri-t-butoxyaluminiumhydrid umgesetzt, im Falle der Herstellung von Verbindungen der Formel IX" unter den obigen Bedingungen mit 1 Mol Methyllithium oder Methylmagnesiumhalid umgesetzt.
Die von der Formel II umfassten Verbindungen, worin R1, R2, m und X' obige Bedeutung haben, lassen sich schliesslich herstellen, indem man Verbindungen der Formel IX' bzw. IX", worin R2 obige Bedeutung hat, mit einem Phosphoniumsalz der Formel X, worin m und X' obige Bedeutung besitzen und r für C, Br oder 1 steht, umsetzt und das so erhaltene Kondensat katalytisch hydriert.
Die neuen Verbindungen der Formel I sind äusserst wirksam in der Erzeugung verschiedener biologischer Reaktionen und eignen sich daher für pharmakologische Zwecke. Einige dieser Reaktionen sind beispielsweise folgende: eine Uterusstimulierende Wirkung sowie eine Blutdrucksenkung.
Die neuen Verbindungen der Formel I waren am Uterus in vitro in Dosen von 1 bis 10 mg/l wirksam, am Uterus in situ in Dosen von 40 bis 2000 ,ug/kg uteroton und blutdrucksenkend und am Rattenmagenstreifen und Colon in Dosen von 1 bis 100 jug wirksam.
Die neuen Verbindungen eignen sich vor allem zur Behandlung der essentiellen Hypertonie, zur Einleitung der Geburt, zur Elimination eines verhaltenen Abortes, zur Schwangerschaftsunterbrechung und zur Mensesinduktion.
Die zu verabreichenden Mengen liegen bei grösseren Säugetieren und beim Menschen in Dosen von 10-500 mg pro Tag je nach Applikationsart.
Die neuen Verbindungen können in verschiedenen Dosierungsformen verabreicht werden, beispielsweise oral in Form von Tabletten, Kapseln oder Flüssigkeiten, rektal in Form von Suppositorien oder subkutan, intramuskulär oder intravenös.
Als Heilmittel können die neuen Verbindungen in geeigneter Arzneiform mit pharmakologisch indifferenten Hilfsstoffen verabreicht werden.
In den nachfolgenden Beispielen erfolgen alle Temperaturangaben in Celsiusgraden.
EMI2.1
Beispiel 1 d, l-4-6'-Carbohexyl-3 -3'-hydroxyoctylphenol
Zu einer Lösung von 2,32 g d,l-1-6'-Carbohexyl-2,3'- hydroxyoctyl-4-methoxybenzol in 80 ml Methylenchlorid wird bei - 700 2,0 ml Bortribromid in 25 nil Methylenchlorid gegeben; dann wurde die Temperatur innerhalb 2 Stunden allmählich auf 0 erhöht. Eis wurde nun zugegeben, die organische Schicht gewaschen, getrocknet und eingedampft. Das so erhaltene Rohprodukt wird an einer Kieselgelsäule gereinigt:
Rf an Kieselgelplatten MN Polyrams neutral, in Toluol/ Aceton/Eisessig = 75:24,5:0,5 1,08 grösser als dasjenige des Ausgangsmaterials.
Das 100 mc NMR (CDCl3) zeigte 3 H bei 8 6,5-7,06 (m); 1 H bei d 4,07 (m); 26 H bei 8 1,1-3,0 (m) und 3 H bei a 0,9 (m).
Das als Ausgangsmaterial verwendete d,1-1-6'-Carboxy- hexyl-2,3'-hydroxyoctyl-4-methoxybenzol wird wie folgt hergestellt: a) 6-Methoxy-2-pentyl-1,2,3,4-tetrahydronaphthalin-1-on
Ein Gemisch von 100 g 6-Methoxy-l-tetralon und 120 g Cyclohexylamin in 500 ml Xylol wird unter einem Wasserabscheider gekocht. Nach 22 Stunden wird das Xylol im Vakuum abgedampft. Der kristalline Rückstand wird in 450 ml Tetrahydrofuran gelöst und bei 200 zu einer aus 87,3 g Diisopropylamin, 434 ml 2 M n-Butyllithium/Hexan und 1500 ml Tetrahydrofuran hergestellten Lithium-diisopropylaminlösung gegeben. Jetzt wird noch 130 g l-Brompentan zugegeben und das Gemisch 90 Minuten unter Rückfluss gekocht. Nach Kühlung auf 50 wird vorsichtig ein Gemisch von 500 g Natriumacetat, 1 Liter Eisessig und 1 Liter Wasser zugegeben und nochmals 90 Minuten gekocht.
Es wird mit Benzol extrahiert, die benzolschen Schichten werden mit 1 N Salzsäure und Wasser gewaschen. Das durch Abdampfen des Benzols erhaltene Rohprodukt wird durch Säulenchromatographie von einer kleinen Menge unreagiertem Ausgangsmaterial befreit und aus Petroläther kristallisiert, Smp.
39-40".
b) 6-Methoxy-2-pentyl-1,2,3,4-tetrahydronaphthalln-1-ol
Eine Lösung von 77,7 g des Produktes (Beispiel la) in 800 ml Methylenchlorid wird unter Rühren zu 22,7 g Natriumborhydrid in 800 ml Äthanol gegeben und das Gemisch 8 Stunden gekocht. Nach Abkühlung wird eine 10 0/0 Natriumbitartrat-Lösung zugetropft und auf die übliche Art aufgearbeitet. Das ölige Produkt wird weiterverwendet.
c) 6-Methoxy-2-pentyl-3,4-dihydronaphthalin
Zu einer Lösung von 30,5 g des Produktes (Beispiel lb) in 150 ml Methylenchlorid wird bei 200 0,06 g Triphenylphosphin-hydrobromid zugegeben. Nach 2 Stunden wird die Lösung vom ausgeschiedenen Wasser getrennt, gewaschen und über Natriumsulfat getrocknet. Das nach Abdampfen des Methylenchlorids erhaltene Rohprodukt wird im Hochva kuum (Badtemperatur 85-900) destilliert und sofort weiterverwendet.
d) 2-3'-Ketooctyl-4-methoxybenzaldehyd
In eine Lösung des Produktes aus dem Beispiel 1c (26,7 g) in 600 ml Methylenchlorid wird bei - 750 so lange ein 3,6 o/o Ozon enthaltender Sauerstoffstrom geleitet, bis die blaue Farbe des Ozonüberschusses merkbar wird. Dann wird die kalte Lösung zu einem Gemisch von 50 g Zink und 150 ml Eisessig gegeben und unter Rühren auf Raumtemperatur gebracht. Nach Filtrierung wird die Lösung mit Wasser gewaschen, getrocknet und eingedampft, wobei das Titelprodukt als Öl erhalten wird.
e) 2-3'-Hydroxyoctyl-4-methoxybenzaldehyd
Eine Lösung des Produktes aus Beispiel 1d (27,4 g) in 400 ml Tetrahydrofuran wird bei - 700 mit 18,25 g Lithium- tri-t-butoxyaluminiumhydrid versetzt und nach 2 Stunden Rühren bei dieser Temperatur langsam (8 Stunden) auf Zimmertemperatur gebracht. Nach Zugabe von 6 ml Wasser und 25 g Natriumsulfat werden die Festsubstanzen entfernt und die organische Lösung zur Trockne gedampft. Der Rückstand wird an einer Kieselgelsäule chromatographiert, wobei das ölige Produkt mit Benzol in reiner Form eluiert werden kann.
f) d, 1-1-6'-Carboxyhexyl-2-3'-hydroxyoctvl-4-methoxybenzol
Zu einer Natrium-methylsulfinyllösungX hergestellt aus 9,3 g Natriumhydrid und 300 ml Dimethylsulfoxid, wird 85 g 6-Carboxyhexyl-triphenylphosphoniumbromid gegeben. Die so erhaltene rote Ylidlösung wird bei 10-150 zu einer Lösung von 21,40 g 2,3'-Hydroxyoctyl-4-methoxybenzaldehyd in 20 ml Dimethylsulfoxid gegeben.-Nach 2v2 Stunden bei 220 werden 1,3 Liter Äther und 2 Liter Wasser zugefügt, die Ätherschicht nach Ansäuerung mit 2 N Salzsäure getrennt und aufgearbeitet.
Das Zwischenprodukt (cis/trans ungesättigten Säuren) wird in 250 mlEisessig gelöst und inAnwesenheit von 3 g Palladium/Kohle bei 500 und einem Wasserstoffdruck von etwa 3 atü hydriert. Nach Aufnahme von einem Squi- valent des Wasserstoffes wird filtriert und eingedampft. Das so erhaltene Rohprodukt wird durch Kieselgelchromatogra phie gereinigt.
Beispiel 2 d, 1-4-6'-Carboxyhexyl-3-5'-p-fluorphenyl-3'- hydroxyp entyl-phenol
Die Titelverbindung wird analog Beispiel 1 hergestellt.
Das als Ausgangsmaterial verwendete 2-p-Fluorphen äthyl-6-methoxy-1,2,3,44etrahydronaphthalin-1-on wird analog Beispiel la hergestellt.
Das als Ausgangsmaterial verwendete 2-p-Fluorphenäthyl- 6-methoxy-1,2,3,4-tetrahydronaphthalin-1-on wird analog Beispiel 1b hergestellt.
Das als Ausgangsmaterial verwendete 2-p-Fluorphen äthyl-6-methoxy-3,4-dihydronaphthalin wird analog Beispiel 1c hergestellt.
Das als Ausgangsmaterial verwendete 2-3'-Keto-5'-pfluorphenylpentyl-4-methoxybenzaldehyd wird analog Beispiel 1d hergestellt.
Das als Ausgangsmaterial verwendete 2-3'-Hydroxy-5-pfluorphenylpentyl-4-methoxybenzaldehyd wird analog Beispiel le hergestellt.
Das als Ausgangsmaterial verwendete d,l-4-6'-Carboxy hexyl-2-5'-p-fluorphenyl-3'-hydroxypentyl-4'-methoxybenzol wird analog Beispiel 1f hergestellt.
Beispiel 3 d, 1-4-5'-5"-Tetrazolylpentyl-3 -3'-hydroxy-3'- methyloctyl-phenol
Die Titelverbindung wird analog Beispiel 1 hergestellt.
The invention relates to a process for the preparation of new phenol derivatives of the formula I (see formula sheet), in which R1 is hydrogen or methyl, R2 is alkyl having 5 to 8 carbon atoms or the remainder
EMI1.1
where Z represents the radical hydrogen, fluorine or chlorine, m the number 5 or 6 and X the radicals
EMI1.2
or -CORs, where Rs represents hydroxy, lower alkoxy or the amino group.
The compounds of the formula I in which X is the radical -COOH can be converted into pharmacologically acceptable salts. Pharmacologically acceptable salts are those with pharmacologically acceptable metal cations, ammonium and amine cations or quaternary ammonium cations.
According to the invention, compounds of the formula I are obtained by adding compounds of the formula II in which R1, R2 and m are as defined above and X 'is the radicals
EMI1.3
or -COOH is subjected to ether cleavage and a) optionally in the case of the preparation of compounds of the formula I in which X is the radical -COR3, where R3 is lower alkoxy or the amino group, compounds of the formula I 'in which Rt, R2 and m have the above meaning and X 'denotes the radical -COOH, esterified or converted into the amide group by methods known per se, or b) optionally in the case of the preparation of pharmaceutically acceptable salts of compounds of the formula I in which X denotes the radical -COOH , Compounds of the formula I ', in which R1, R2, m and X' have the above meaning,
treated with inorganic or organic bases
The ether cleavage is carried out by methods known per se, for example with a boron trihalide, preferably boron tribromide, or hydrogen halide, preferably hydrogen bromide, in a solvent which is inert under the reaction conditions, such as. B. methylene chloride or chloroform at temperatures of - 700 and + 200.
The compounds of formula II used as starting material are prepared by reacting 6-methoxy-tetralone (formula III) with a compound of formula IV, in which R2 has the above meaning and A stands for iodine, bromine, chlorine, -O-tosyl or O- Mesyl stands, implements. Here, the imide is first prepared with cyclohexylamine in boiling xylene, the latter is first reacted in tetrahydrofuran with lithium diisopropylamide, then with 1.0 to 1.3 mol of a compound of the formula IV and the resulting product is hydrolyzed with aqueous acetic acid, a compound of the formula V arises. The latter is reduced with a complex hydride, preferably with sodium borohydride in methylene chloride / ethanol at temperatures from 0 to 600 ° C., a compound of the formula VI being formed.
The latter is converted to compounds of the formula VII under acid catalysis. The use of catalytic amounts of triphenylphosphine hydrobromide in a solution of methylene chloride at temperatures between 0 and 280 C. The compounds of the formula VII are then subjected to ozone decomposition. For this purpose, they are treated with ozone-containing (1-7 / o) oxygen in a solution of methylene chloride at temperatures of -80 to -600 C until 1 mole of ozone has been absorbed. Then zinc and acetic acid are added, the mixture is brought to 250 ° C. with stirring, compounds of the formula VIII being formed.
In the case of the preparation of compounds of the formula IX ', the latter are reacted with 1 mol of lithium tri-t-butoxyaluminum hydride at a temperature of -80 and-150 ° C. in diglyme, tetrahydrofuran or ether as the solvent, in the case of the preparation of compounds of the formula IX "reacted under the above conditions with 1 mol of methyl lithium or methyl magnesium halide.
The compounds encompassed by formula II, in which R1, R2, m and X 'have the above meaning, can finally be prepared by combining compounds of the formula IX' or IX '', in which R2 has the above meaning, with a phosphonium salt of the formula X. , where m and X 'have the above meaning and r is C, Br or 1, is reacted and the condensate thus obtained is catalytically hydrogenated.
The new compounds of the formula I are extremely effective in generating various biological reactions and are therefore suitable for pharmacological purposes. Some of these reactions are, for example: a uterine-stimulating effect and a decrease in blood pressure.
The new compounds of the formula I were effective on the uterus in vitro in doses of 1 to 10 mg / l, on the uterus in situ in doses of 40 to 2000, uterotonic and antihypertensive ug / kg and on the rat stomach strip and colon in doses of 1 to 100 jug effective.
The new compounds are particularly suitable for the treatment of essential hypertension, for inducing childbirth, for eliminating a restrained abortion, for interrupting pregnancy and for inducing menses.
The amounts to be administered are in larger mammals and in humans in doses of 10-500 mg per day depending on the type of application.
The new compounds can be administered in various dosage forms, for example orally in the form of tablets, capsules or liquids, rectally in the form of suppositories or subcutaneously, intramuscularly or intravenously.
The new compounds can be administered as medicaments in a suitable drug form with pharmacologically inert adjuvants.
In the following examples, all temperatures are given in degrees Celsius.
EMI2.1
Example 1 d, 1-4-6'-Carbohexyl-3 -3'-hydroxyoctylphenol
To a solution of 2.32 g of d, l-1-6'-carbohexyl-2,3'-hydroxyoctyl-4-methoxybenzene in 80 ml of methylene chloride, 2.0 ml of boron tribromide in 25 nil of methylene chloride is added at - 700; then the temperature was gradually increased to 0 over 2 hours. Ice was then added, the organic layer was washed, dried and evaporated. The crude product obtained in this way is purified on a silica gel column:
Rf on silica gel plates MN Polyrams neutral, in toluene / acetone / glacial acetic acid = 75: 24.5: 0.5 1.08 greater than that of the starting material.
The 100 mc NMR (CDCl3) showed 3 H at 8 6.5-7.06 (m); 1 H at d 4.07 (m); 26 H at 8 1.1-3.0 (m) and 3 H at a 0.9 (m).
The d, 1-1-6'-carboxyhexyl-2,3'-hydroxyoctyl-4-methoxybenzene used as starting material is prepared as follows: a) 6-methoxy-2-pentyl-1,2,3,4- tetrahydronaphthalen-1-one
A mixture of 100 g of 6-methoxy-1-tetralone and 120 g of cyclohexylamine in 500 ml of xylene is boiled under a water separator. After 22 hours the xylene is evaporated off in vacuo. The crystalline residue is dissolved in 450 ml of tetrahydrofuran and added at 200 to a lithium diisopropylamine solution prepared from 87.3 g of diisopropylamine, 434 ml of 2M n-butyllithium / hexane and 1500 ml of tetrahydrofuran. 130 g of 1-bromopentane are now added and the mixture is refluxed for 90 minutes. After cooling to 50, a mixture of 500 g of sodium acetate, 1 liter of glacial acetic acid and 1 liter of water is carefully added and the mixture is boiled for another 90 minutes.
It is extracted with benzene, the benzene layers are washed with 1N hydrochloric acid and water. The crude product obtained by evaporating off the benzene is freed from a small amount of unreacted starting material by column chromatography and crystallized from petroleum ether, mp.
39-40 ".
b) 6-methoxy-2-pentyl-1,2,3,4-tetrahydronaphthalln-1-ol
A solution of 77.7 g of the product (Example la) in 800 ml of methylene chloride is added with stirring to 22.7 g of sodium borohydride in 800 ml of ethanol and the mixture is boiled for 8 hours. After cooling, a 10% sodium bitartrate solution is added dropwise and worked up in the usual way. The oily product is used further.
c) 6-methoxy-2-pentyl-3,4-dihydronaphthalene
To a solution of 30.5 g of the product (Example Ib) in 150 ml of methylene chloride, 0.06 g of triphenylphosphine hydrobromide is added at 200. After 2 hours the solution is separated from the precipitated water, washed and dried over sodium sulfate. The crude product obtained after evaporation of the methylene chloride is distilled in a high vacuum (bath temperature 85-900) and used immediately.
d) 2-3'-ketooctyl-4-methoxybenzaldehyde
A stream of oxygen containing 3.6 o / o ozone is passed into a solution of the product from Example 1c (26.7 g) in 600 ml of methylene chloride at -750 until the blue color of the excess ozone is noticeable. The cold solution is then added to a mixture of 50 g of zinc and 150 ml of glacial acetic acid and brought to room temperature with stirring. After filtering, the solution is washed with water, dried and evaporated to give the title product as an oil.
e) 2-3'-hydroxyoctyl-4-methoxybenzaldehyde
A solution of the product from Example 1d (27.4 g) in 400 ml of tetrahydrofuran is treated at -700 with 18.25 g of lithium tri-t-butoxyaluminum hydride and, after stirring for 2 hours at this temperature, slowly (8 hours) brought to room temperature . After adding 6 ml of water and 25 g of sodium sulfate, the solids are removed and the organic solution is evaporated to dryness. The residue is chromatographed on a silica gel column, and the oily product can be eluted in pure form with benzene.
f) d, 1-1-6'-carboxyhexyl-2-3'-hydroxyoctvl-4-methoxybenzene
85 g of 6-carboxyhexyl-triphenylphosphonium bromide are added to a sodium methylsulfinyl solution X prepared from 9.3 g of sodium hydride and 300 ml of dimethyl sulfoxide. The red ylide solution thus obtained is added at 10-150 to a solution of 21.40 g of 2,3'-hydroxyoctyl-4-methoxybenzaldehyde in 20 ml of dimethyl sulfoxide. After 2/2 hours at 220, 1.3 liters of ether and 2 liters of water are added added, the ether layer separated after acidification with 2N hydrochloric acid and worked up.
The intermediate product (cis / trans unsaturated acids) is dissolved in 250 ml of glacial acetic acid and hydrogenated in the presence of 3 g of palladium / carbon at 500 and a hydrogen pressure of about 3 atm. After taking up one equivalent of the hydrogen, it is filtered and evaporated. The crude product obtained in this way is purified by silica gel chromatography.
Example 2 d, 1-4-6'-carboxyhexyl-3-5'-p-fluorophenyl-3'-hydroxypentyl-phenol
The title compound is prepared analogously to Example 1.
The 2-p-fluorophen used as starting material ethyl-6-methoxy-1,2,3,44etrahydronaphthalen-1-one is prepared analogously to Example la.
The 2-p-fluorophenethyl-6-methoxy-1,2,3,4-tetrahydronaphthalen-1-one used as starting material is prepared analogously to Example 1b.
The 2-p-fluorophen used as the starting material ethyl-6-methoxy-3,4-dihydronaphthalene is prepared analogously to Example 1c.
The 2-3'-keto-5'-fluorophenylpentyl-4-methoxybenzaldehyde used as starting material is prepared analogously to Example 1d.
The 2-3'-hydroxy-5-fluorophenylpentyl-4-methoxybenzaldehyde used as starting material is prepared analogously to Example le.
The d, 1-4-6'-carboxyhexyl-2-5'-p-fluorophenyl-3'-hydroxypentyl-4'-methoxybenzene used as starting material is prepared analogously to Example 1f.
Example 3 d, 1-4-5'-5 "-Tetrazolylpentyl-3 -3'-hydroxy-3'-methyloctyl-phenol
The title compound is prepared analogously to Example 1.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1125174A CH599182A5 (en) | 1974-08-16 | 1974-08-16 | 3-Hydroxy-alkyl-4-carboxy-alkyl-phenol derivs. prepn. |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1125174A CH599182A5 (en) | 1974-08-16 | 1974-08-16 | 3-Hydroxy-alkyl-4-carboxy-alkyl-phenol derivs. prepn. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH599182A5 true CH599182A5 (en) | 1978-05-12 |
Family
ID=4371647
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1125174A CH599182A5 (en) | 1974-08-16 | 1974-08-16 | 3-Hydroxy-alkyl-4-carboxy-alkyl-phenol derivs. prepn. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH599182A5 (en) |
-
1974
- 1974-08-16 CH CH1125174A patent/CH599182A5/en not_active IP Right Cessation
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