NO128604B - - Google Patents
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- Publication number
- NO128604B NO128604B NO514569A NO514569A NO128604B NO 128604 B NO128604 B NO 128604B NO 514569 A NO514569 A NO 514569A NO 514569 A NO514569 A NO 514569A NO 128604 B NO128604 B NO 128604B
- Authority
- NO
- Norway
- Prior art keywords
- methoxy
- naphthyl
- formula
- compound
- ether
- Prior art date
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 84
- 150000001875 compounds Chemical class 0.000 claims description 29
- 238000000034 method Methods 0.000 claims description 28
- 239000011541 reaction mixture Substances 0.000 claims description 25
- 239000000203 mixture Substances 0.000 claims description 23
- LTRANDSQVZFZDG-UHFFFAOYSA-N 2-(6-methoxynaphthalen-2-yl)propan-1-ol Chemical compound C1=C(C(C)CO)C=CC2=CC(OC)=CC=C21 LTRANDSQVZFZDG-UHFFFAOYSA-N 0.000 claims description 16
- -1 2-(6-methoxy-2-naphthyl)-1-propyl Chemical group 0.000 claims description 13
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 13
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 12
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 10
- 229910052700 potassium Inorganic materials 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 7
- 239000003054 catalyst Substances 0.000 claims description 7
- 229910052744 lithium Inorganic materials 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- MJWURUPGNUFKMR-UHFFFAOYSA-N 2-(6-methoxynaphthalen-2-yl)prop-2-enoic acid Chemical compound C1=C(C(=C)C(O)=O)C=CC2=CC(OC)=CC=C21 MJWURUPGNUFKMR-UHFFFAOYSA-N 0.000 claims description 5
- 238000005984 hydrogenation reaction Methods 0.000 claims description 5
- 229910052987 metal hydride Inorganic materials 0.000 claims description 5
- 150000004681 metal hydrides Chemical class 0.000 claims description 5
- UPEGIZOAIZVQDQ-UHFFFAOYSA-N 2-(6-methoxynaphthalen-2-yl)-2-methyloxirane Chemical compound C1=CC2=CC(OC)=CC=C2C=C1C1(C)CO1 UPEGIZOAIZVQDQ-UHFFFAOYSA-N 0.000 claims description 4
- VDWXOLWUMXBPHB-UHFFFAOYSA-N 2-(6-methoxynaphthalen-2-yl)prop-2-en-1-ol Chemical compound C1=C(C(=C)CO)C=CC2=CC(OC)=CC=C21 VDWXOLWUMXBPHB-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 239000002841 Lewis acid Substances 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 150000007529 inorganic bases Chemical class 0.000 claims description 3
- 150000007517 lewis acids Chemical class 0.000 claims description 3
- 230000001225 therapeutic effect Effects 0.000 claims description 3
- DVQOTDYKJNEHNJ-UHFFFAOYSA-N 2-methoxy-6-prop-2-enylnaphthalene Chemical compound C1=C(CC=C)C=CC2=CC(OC)=CC=C21 DVQOTDYKJNEHNJ-UHFFFAOYSA-N 0.000 claims description 2
- 239000007795 chemical reaction product Substances 0.000 claims description 2
- 229910052725 zinc Inorganic materials 0.000 claims description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
- 238000006243 chemical reaction Methods 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- 239000000243 solution Substances 0.000 description 17
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 16
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- YKYOUMDCQGMQQO-UHFFFAOYSA-L cadmium dichloride Chemical compound Cl[Cd]Cl YKYOUMDCQGMQQO-UHFFFAOYSA-L 0.000 description 8
- KDCIHNCMPUBDKT-UHFFFAOYSA-N hexane;propan-2-one Chemical compound CC(C)=O.CCCCCC KDCIHNCMPUBDKT-UHFFFAOYSA-N 0.000 description 8
- 239000012071 phase Substances 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 6
- 239000011591 potassium Substances 0.000 description 6
- 238000007796 conventional method Methods 0.000 description 5
- 150000002170 ethers Chemical class 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 230000035484 reaction time Effects 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- GGWCZBGAIGGTDA-UHFFFAOYSA-N 1-(6-methoxynaphthalen-2-yl)ethanone Chemical compound C1=C(C(C)=O)C=CC2=CC(OC)=CC=C21 GGWCZBGAIGGTDA-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- 229930040373 Paraformaldehyde Natural products 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- MBRGPNPWNNBULN-UHFFFAOYSA-M [Br-].COC=1C=C2C=CC(=CC2=CC1)C(C)[Mg+] Chemical compound [Br-].COC=1C=C2C=CC(=CC2=CC1)C(C)[Mg+] MBRGPNPWNNBULN-UHFFFAOYSA-M 0.000 description 3
- KMPWYEUPVWOPIM-KODHJQJWSA-N cinchonidine Chemical compound C1=CC=C2C([C@H]([C@H]3[N@]4CC[C@H]([C@H](C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-KODHJQJWSA-N 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 229920002866 paraformaldehyde Polymers 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- LUZDYPLAQQGJEA-UHFFFAOYSA-N 2-Methoxynaphthalene Chemical compound C1=CC=CC2=CC(OC)=CC=C21 LUZDYPLAQQGJEA-UHFFFAOYSA-N 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 229910015900 BF3 Inorganic materials 0.000 description 2
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
- CEERUWZBFFNSRP-UHFFFAOYSA-N COC=1C=C2C=CC(=CC2=CC1)C(C)[Cd] Chemical compound COC=1C=C2C=CC(=CC2=CC1)C(C)[Cd] CEERUWZBFFNSRP-UHFFFAOYSA-N 0.000 description 2
- RQCKEFHDNCHKCZ-UHFFFAOYSA-N COC=1C=C2C=CC(=CC2=CC1)C(C)[Na] Chemical compound COC=1C=C2C=CC(=CC2=CC1)C(C)[Na] RQCKEFHDNCHKCZ-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 206010061218 Inflammation Diseases 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- 239000012448 Lithium borohydride Substances 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
- 239000012346 acetyl chloride Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 150000001639 boron compounds Chemical class 0.000 description 2
- KMPWYEUPVWOPIM-UHFFFAOYSA-N cinchonidine Natural products C1=CC=C2C(C(C3N4CCC(C(C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N o-dicarboxybenzene Natural products OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 230000020477 pH reduction Effects 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 229910052703 rhodium Inorganic materials 0.000 description 2
- 239000010948 rhodium Substances 0.000 description 2
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- PUGUQINMNYINPK-UHFFFAOYSA-N tert-butyl 4-(2-chloroacetyl)piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCN(C(=O)CCl)CC1 PUGUQINMNYINPK-UHFFFAOYSA-N 0.000 description 2
- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 2
- VFJYIHQDILEQNR-UHFFFAOYSA-M trimethylsulfanium;iodide Chemical compound [I-].C[S+](C)C VFJYIHQDILEQNR-UHFFFAOYSA-M 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N 1-propanol Substances CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- XEEITBAXIABDJT-UHFFFAOYSA-N 2-(1-bromoethyl)-6-methoxynaphthalene Chemical compound C1=C(C(C)Br)C=CC2=CC(OC)=CC=C21 XEEITBAXIABDJT-UHFFFAOYSA-N 0.000 description 1
- CMWTZPSULFXXJA-UHFFFAOYSA-N 2-(6-methoxy-2-naphthalenyl)propanoic acid Chemical compound C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
- 208000010392 Bone Fractures Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- BGLUHKXZAFGLNM-UHFFFAOYSA-N COC=1C=C2C=CC(=CC2=CC1)C(C)[K] Chemical compound COC=1C=C2C=CC(=CC2=CC1)C(C)[K] BGLUHKXZAFGLNM-UHFFFAOYSA-N 0.000 description 1
- ZALIYRZMVXSJPM-UHFFFAOYSA-N COC=1C=C2C=CC(=CC2=CC1)C(C)[Li] Chemical compound COC=1C=C2C=CC(=CC2=CC1)C(C)[Li] ZALIYRZMVXSJPM-UHFFFAOYSA-N 0.000 description 1
- QFCVSLOOCXNECI-UHFFFAOYSA-N COC=1C=C2C=CC(=CC2=CC1)C(C)[Zn] Chemical compound COC=1C=C2C=CC(=CC2=CC1)C(C)[Zn] QFCVSLOOCXNECI-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 206010010254 Concussion Diseases 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000006670 Multiple fractures Diseases 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- LGRFSURHDFAFJT-UHFFFAOYSA-N Phthalic anhydride Natural products C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- ZLNQCMDQGHYICR-UHFFFAOYSA-M [Cl-].COC=1C=C2C=CC(=CC2=CC1)C(C)[Mg+] Chemical compound [Cl-].COC=1C=C2C=CC(=CC2=CC1)C(C)[Mg+] ZLNQCMDQGHYICR-UHFFFAOYSA-M 0.000 description 1
- HQFSKHGKXPADLC-UHFFFAOYSA-M [I-].COC=1C=C2C=CC(=CC2=CC1)C(C)[Mg+] Chemical compound [I-].COC=1C=C2C=CC(=CC2=CC1)C(C)[Mg+] HQFSKHGKXPADLC-UHFFFAOYSA-M 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical class B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- JHIWVOJDXOSYLW-UHFFFAOYSA-N butyl 2,2-difluorocyclopropane-1-carboxylate Chemical compound CCCCOC(=O)C1CC1(F)F JHIWVOJDXOSYLW-UHFFFAOYSA-N 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000009514 concussion Effects 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Inorganic materials [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 1
- HSZCZNFXUDYRKD-UHFFFAOYSA-M lithium iodide Inorganic materials [Li+].[I-] HSZCZNFXUDYRKD-UHFFFAOYSA-M 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 210000002346 musculoskeletal system Anatomy 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
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
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/027—Organoboranes and organoborohydrides
-
- 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
- C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
- C07C45/46—Friedel-Crafts reactions
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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
- C07F1/00—Compounds containing elements of Groups 1 or 11 of the Periodic Table
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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
- C07F3/00—Compounds containing elements of Groups 2 or 12 of the Periodic Table
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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
- C07F3/00—Compounds containing elements of Groups 2 or 12 of the Periodic Table
- C07F3/02—Magnesium compounds
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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
- C07F3/00—Compounds containing elements of Groups 2 or 12 of the Periodic Table
- C07F3/06—Zinc compounds
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- Chemical & Material Sciences (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
Analogifremgangsmåter for fremstilling av 2-(6-metoksy-2-naftyl)-propanol med terapeutisk virkning, Analogous methods for the production of 2-(6-methoxy-2-naphthyl)-propanol with therapeutic effect,
Foreliggende oppfinnelse angår en analogifremgangsmåte til fremstilling av 2-(6-metoksy-2-naftyl)propanol med terapeutisk virkning, The present invention relates to an analogue method for the production of 2-(6-methoxy-2-naphthyl)propanol with a therapeutic effect,
som er en videreutvikling av oppfinnelsen ifølge påtent nr. 125.971. which is a further development of the invention according to patent no. 125,971.
Dette patent vedrører fremstilling av bestemte 6-substituerte &-(2-naftyl)-a-metyletanoler samt acetylestere derav. Foreliggende oppfinnelse omhandler nye analogifremgangsmåter for fremstilling av nevnte propanolforbindelse samt optisk aktive isomere derav. This patent relates to the production of certain 6-substituted &-(2-naphthyl)-a-methylethanols as well as acetyl esters thereof. The present invention relates to new analogue methods for the production of said propanol compound as well as optically active isomers thereof.
En første fremgangsmåte ifølge foreliggende oppfinnelse for fremstilling av 2-(6-metoksy-2-naftyl)-1-propanol omfatter at man omsetter A first method according to the present invention for the production of 2-(6-methoxy-2-naphthyl)-1-propanol comprises reacting
en borforbindelse med formelen: a boron compound with the formula:
hvor R<1> er 2-(6-metoksy-2-naftyl)-l-propy1 med hydrogenperoksyd i en vandig oppløsning av en uorganisk base. Borforbindelsen where R<1> is 2-(6-methoxy-2-naphthyl)-1-propyl with hydrogen peroxide in an aqueous solution of an inorganic base. The boron compound
fremstilles ved at man i en eter omsetter 6-metoksy-2-(2-propeny1)-naftalen med diboran. is prepared by reacting 6-methoxy-2-(2-propenyl)-naphthalene with diborane in an ether.
En annen analogifremgangsmåte omfatter at man omsetter en forbindelse med formelen: Another method of analogy involves reacting a compound with the formula:
hvor M er MgCl, MgBr, Mgl, Li, Na, K, Zn^ eller Cd^ med formaldehyd og behandler reaksjonsblandingen med en syre. where M is MgCl, MgBr, Mgl, Li, Na, K, Zn^ or Cd^ with formaldehyde and treating the reaction mixture with an acid.
En tredje analogifremgangsmåte innbefatter at man omsetter 2-(6-metoksy-2-naftyl)-propylenoksyd med et metallhydrid i nærvær av aluminiumklorid eller en ekvivalent Lewis-syre i en eter inntil man får fremstilt 2-(6-metoksy-2-naftyl)-l-propanol. A third analogous procedure involves reacting 2-(6-methoxy-2-naphthyl)-propylene oxide with a metal hydride in the presence of aluminum chloride or an equivalent Lewis acid in an ether until 2-(6-methoxy-2-naphthyl) is obtained )-1-propanol.
En fjerde analogifremgangsmåte innbefatter at man omsetter 2-(6-metoksy-2-naftyl)-2-propen-l-ol med hydrogen i nærvær av en hydrogeneringskatalysator i et inert organisk oppløsnings-middel. A fourth analogous method involves reacting 2-(6-methoxy-2-naphthyl)-2-propen-1-ol with hydrogen in the presence of a hydrogenation catalyst in an inert organic solvent.
En femte analogifremgangsmåte innbefatter at man omsetter 2-(6-metoksy-2-naftyl)-akrylsyre med diboran i en eter. A fifth analogous procedure involves reacting 2-(6-methoxy-2-naphthyl)-acrylic acid with diborane in an ether.
I de forannevnte fremgangsmåter hvor produktet blir fremstilt som en racemisk blanding, kan nevnte blanding spaltes optisk slik at man får fremstilt 1-2-(6-metoksy-2-naftyl)-l-propanol, even-tuelt d-2-(6-metoksy-2-naftyl)-l-propanol. In the aforementioned methods where the product is prepared as a racemic mixture, said mixture can be optically resolved so that 1-2-(6-methoxy-2-naphthyl)-1-propanol, possibly d-2-(6 -methoxy-2-naphthyl)-1-propanol.
Den første ovenfor angitte alternative fremgangsmåte kan angis ved følgende formler: The first alternative method indicated above can be expressed by the following formulas:
De trisubstituerte boraner med formel Ia fremstilles ved å omsette en forbindelse med formel I med diboran i en eter. The trisubstituted boranes of formula Ia are prepared by reacting a compound of formula I with diborane in an ether.
De etere som er godt egnet for denne omsetning er ikke kritisk. Egnede etere innbefatter dietyleter, diglym og tetrahydrofuran. The ethers which are well suited for this turnover are not critical. Suitable ethers include diethyl ether, diglyme and tetrahydrofuran.
Reaksjonen kan utføres ved temperaturer fra 0° til 40°C. Den nødvendige reaksjonstid er avhengig av temperaturen og vanligvis vil tider fra 1 til 6 timer være tilstrekkelig. The reaction can be carried out at temperatures from 0° to 40°C. The required reaction time depends on the temperature and usually times from 1 to 6 hours will be sufficient.
Forbindelsen med formel II fremstilles ved å behandle forbindelsen med formel Ia med hydrogenperoksyd i en vandig oppløsning av en uorganisk base, slik som et alkalimetallhydroksyd eller karbonat, f.eks. natriumhydroksyd, litiumhydroksyd, kaliumhydroksyd, natriumkarbonat og kaliumkarbonat. Basekonsentrasjonen i oppløs-ningen kan variere fra 1 til 10 vektprosent. Mengden av hydrogenperoksyd i oppløsningen bør være minst 3, fortrinnsvis ca. 5 mol ekvivalenter. The compound of formula II is prepared by treating the compound of formula Ia with hydrogen peroxide in an aqueous solution of an inorganic base, such as an alkali metal hydroxide or carbonate, e.g. sodium hydroxide, lithium hydroxide, potassium hydroxide, sodium carbonate and potassium carbonate. The base concentration in the solution can vary from 1 to 10 percent by weight. The amount of hydrogen peroxide in the solution should be at least 3, preferably approx. 5 mole equivalents.
Denne reaksjon utføres ved en temperatur fra 0° til 60°C, fortrinnsvis omkring 40°C. Den nødvendige reaksjonstid er avhengig av temperaturen. Vanligvis vil tidsrom fra 30 minutter til 12 timer være tilstrekkelig. Forbindelsen med formel II utskilles så fra reaksjonsblandingen ved vanlig teknikk. F.eks. kan reaksjonsblandingen ekstraheres med eter, eterfasen fordampes til tørrhet, hvorved man får utskilt 2-(6-metoksy-2-naftyl)-l-propanol som omkrystalliseres fra aceton-heksan. Alternativt kan andre teknikker slik som kromatografi anvendes for å isolere forbindelsen med formel II. This reaction is carried out at a temperature from 0° to 60°C, preferably around 40°C. The required reaction time depends on the temperature. Generally, periods of time from 30 minutes to 12 hours will be sufficient. The compound of formula II is then separated from the reaction mixture by conventional techniques. E.g. the reaction mixture can be extracted with ether, the ether phase is evaporated to dryness, whereby 2-(6-methoxy-2-naphthyl)-1-propanol is separated which is recrystallized from acetone-hexane. Alternatively, other techniques such as chromatography can be used to isolate the compound of formula II.
Den foretrukne forbindelse med formel II er 1-2-(6-metoksy-2-naftyl)-l-propanol. Denne kan fremstilles ved optisk spaltning av forbindelser med formel II, f..eks. ved selektiv biologisk ned-brytning eller ved fremstilling av diastereoisomersalter av ftal-syreesteren av 2-(6-metoksy-2-naftyl)-l-propanol med en oppløst optisk aktiv aminbase slik som cinchonidin, hvoretter de dannede isomere utskilles ved fraksjonert krystallisasjon.Det utskilte 1-isomer-salt kan så spaltes til den respektive ester som deretter hydro-lyseres til den tilsvarende forbindelse, nemlig 1-2-(6-metoksy-2- The preferred compound of formula II is 1-2-(6-methoxy-2-naphthyl)-1-propanol. This can be produced by optical cleavage of compounds of formula II, e.g. by selective biological degradation or by the preparation of diastereoisomeric salts of the phthalic acid ester of 2-(6-methoxy-2-naphthyl)-l-propanol with a dissolved optically active amine base such as cinchonidine, after which the formed isomers are separated by fractional crystallization. The secreted 1-isomer salt can then be cleaved to the respective ester which is then hydrolysed to the corresponding compound, namely 1-2-(6-methoxy-2-
s naftyl)-l-p'ropanol. s naphthyl)-l-propanol.
Forbindelsen med formel I kan fremstilles ved å omsette 2-acetyl-6-metoksynaftalen (en kjent forbindelse) med metylmagnesium-bromid i THF ved koketemperatur fulgt av en tilsetning av en mineral-syre og en ytterligere periode med koking, fortynne reaksjonsblandingen med vann og ekstrahere den vandige blanding med kloroform. Kloroformekstraktene kan så tørkes og fordampes til tørrhet, hvorved man får forbindelsen med formel I. The compound of formula I can be prepared by reacting 2-acetyl-6-methoxynaphthalene (a known compound) with methylmagnesium bromide in THF at boiling temperature followed by addition of a mineral acid and a further period of boiling, diluting the reaction mixture with water and extract the aqueous mixture with chloroform. The chloroform extracts can then be dried and evaporated to dryness, whereby the compound of formula I is obtained.
Den andre ovenfor angitte alternative fremgangsmåte kan angis ved følgende formler: The second alternative method indicated above can be expressed by the following formulas:
hvor M er MgCl, MgBr, Mgl, Li, Na, K, Zn-^ eller Cd-^, fortrinnsvis MgCl, MgBr eller Mgl. where M is MgCl, MgBr, Mgl, Li, Na, K, Zn-^ or Cd-^, preferably MgCl, MgBr or Mgl.
Forbindelsen med formel II kan fremstilles ved å behandle forbindelsen med formel Ib med formaldehyd, fortrinnsvis som paraformaldehyd ved en temperatur fra /\. 0°C til blandingens kokepunkt, inntil 1 mol ekvivalent formaldehyd har reagert med forbindelsen med formel Ib. Vanligvis vil et tidsrom fra 1 time til 48 timer være tilstrekkelig for denne reaksjon, og reaksjonstiden er meget avhengig av temperaturen. Reaksjonsblandingen blir så surgjort med en egnet syre, fortrinnsvis en fortynnet syre, hvoretter forbindelsen med formel II utskilles fra reaksjonsblandingen ved vanlig kjent teknikk. F.eks. kan den intermediære reaksjonsblanding fordampes til tørrhet, residuet surgjøres med fortynnet syre og fortynnes så med vann for derved å få utfelt forbindelsen med formel II. Denne kan så utskilles ved filtrering og omkrystalliseres fra aceton-heksan. Alternativt kan forbindelsen med formel II fjernes ved en eterekstraksjon, hvoretter denne fase fordampes til et residuum som omkrystalliseres fra aceton-heksan. Man kan også anvende andre vanlige utskillings-teknikker, såsom kromatografi. The compound of formula II can be prepared by treating the compound of formula Ib with formaldehyde, preferably as paraformaldehyde at a temperature from /\. 0°C to the boiling point of the mixture, until 1 mol equivalent of formaldehyde has reacted with the compound of formula Ib. Usually, a period of time from 1 hour to 48 hours will be sufficient for this reaction, and the reaction time is very dependent on the temperature. The reaction mixture is then acidified with a suitable acid, preferably a dilute acid, after which the compound of formula II is separated from the reaction mixture by conventional techniques. E.g. the intermediate reaction mixture can be evaporated to dryness, the residue acidified with dilute acid and then diluted with water to thereby precipitate the compound of formula II. This can then be separated by filtration and recrystallized from acetone-hexane. Alternatively, the compound of formula II can be removed by an ether extraction, after which this phase is evaporated to a residue which is recrystallized from acetone-hexane. You can also use other common separation techniques, such as chromatography.
Forbindelser med formelen Ib fremstilles ved en fremgangsmåte som kan illustreres på følgende måte: Compounds with the formula Ib are produced by a method that can be illustrated as follows:
hvor Mr-«g^som definert tidligere, mens X er jod, brom eller klor. where Mr-«g^as defined previously, while X is iodine, bromine or chlorine.
Forbindelser med formel (B) fremstilles ved følgende fremgangsmåte: Forbindelsen med formel (A) reduseres til den tilsvarende alkohol ved behandling med natriumborhydrid ved romtemperatur i 30 minutter, fulgt av en forsiktig surgjøring med fortynnet saltsyre, hvoretter reaksjonsblandingen ekstraheres med dietyleter. Eterfasen kan så fordampes til tørrhet, hvormed man får alkoholen. Residuet omsettes med p-toluensulfonylklorid i pyridin ved romtemperatur i ca. 15 timer fulgt av vasking med fortynnet saltsyre, ekstraksjon med eter og fordamping av eterfasen, hvorved man får det tilsvarende p-toluensulfonat. Residuet av denne reaksjon omsettes med et overskudd av litiumhålogenid (litiumbromid, klorid eller jodid) i aceton i 24 timer ved romtemperatur, hvoretter reaksjonsblandingen fortynnes med vann og ekstraheres med eter. Eterfasen fordampes så til tørrhet, hvorved man får en tilsvarende halogenider med formel (B). Compounds of formula (B) are prepared by the following procedure: The compound of formula (A) is reduced to the corresponding alcohol by treatment with sodium borohydride at room temperature for 30 minutes, followed by careful acidification with dilute hydrochloric acid, after which the reaction mixture is extracted with diethyl ether. The ether phase can then be evaporated to dryness, which gives the alcohol. The residue is reacted with p-toluenesulfonyl chloride in pyridine at room temperature for approx. 15 hours followed by washing with dilute hydrochloric acid, extraction with ether and evaporation of the ether phase, whereby the corresponding p-toluenesulfonate is obtained. The residue of this reaction is reacted with an excess of lithium halide (lithium bromide, chloride or iodide) in acetone for 24 hours at room temperature, after which the reaction mixture is diluted with water and extracted with ether. The ether phase is then evaporated to dryness, whereby a corresponding halide with formula (B) is obtained.
Forbindelser med formel Ib hvor M er MgCl, MgBr eller Mgl Compounds of formula Ib where M is MgCl, MgBr or Mgl
(de foretrukne forbindelser) fremstilles ved omsetning av det tilsvarende halogenid med formel (B) i tetrahydrofuran med et overskudd av pulverisert magnesium ved ca. M5°C. Reaksjonsproduktet kan så utskilles fra overskuddet av metallet. Den samme fremgangsmåte kan brukes for å få fremstilt de tilsvarende forbindelser med formel Ib, hvor M er Li eller. Znj ved å erstatte magnesiumpulveret med ét tilsvarende litium- eller sinkpulver.. (the preferred compounds) are prepared by reacting the corresponding halide of formula (B) in tetrahydrofuran with an excess of powdered magnesium at approx. M5°C. The reaction product can then be separated from the excess of the metal. The same procedure can be used to prepare the corresponding compounds of formula Ib, where M is Li or. Znj by replacing the magnesium powder with an equivalent lithium or zinc powder..
Forbindelser med formel Ib, hvor M er Cdj kan fremstilles ved å behandle de tilsvarende forbindelser, hvor M er MgBr med kadmiumklorid i tetrahydrofuran ved romtemperatur i ca. 30 minutter. Ved å gjenta denne fremgangsmåte,, men ved å erstatte kadmiumkloridet med findelt natrium eller kalium, kan. den brukes for å få fremstilt forbindelser med formel Ib, hvor M er Na eller K. Compounds of formula Ib, where M is Cdj can be prepared by treating the corresponding compounds, where M is MgBr with cadmium chloride in tetrahydrofuran at room temperature for approx. 30 minutes. By repeating this procedure, but by replacing the cadmium chloride with finely divided sodium or potassium, can. it is used to obtain compounds of formula Ib, where M is Na or K.
Den tredje ovenfor angitte alternative fremgangsmåte kan angis The third alternative method indicated above may be indicated
Første trinn i denne fremgangsmåte innbefatter åt man omsetter' The first step in this process involves converting
iin
en forbindelse med formel I med et metallhydrid i en eter i ilærvær av aluminiumklorid eller en ekvivalent Lewis-syre. ^ T^ S a compound of formula I with a metal hydride in an ether in ether of aluminum chloride or an equivalent Lewis acid. ^T^S
Egnede metallhydrider innbefatter diboran, litiumaluminiumhydrid, natriumborhydrid, kaliumborhydrid, kaliumborhydrid og litiumborhydrid. Det spesielle metallhydrid er ikke kritisk. Suitable metal hydrides include diborane, lithium aluminum hydride, sodium borohydride, potassium borohydride, potassium borohydride and lithium borohydride. The particular metal hydride is not critical.
Egnede Lev/is-syrer innbefatter aluminiumklorid, bortriklorid, bortrifluorid, bortrifluorid-dietyleter, aluminiumbromid og bortribromid. Suitable Lev's acids include aluminum chloride, boron trichloride, boron trifluoride, boron trifluoride diethyl ether, aluminum bromide and boron tribromide.
Enhver kjent eter kan brukes i denne reaksjon. Egnede etere innbefatter dietyleter, tetrahydropyran, tetrahydrofuran og dimetoksyetan. Reaksjonstemperaturen er ikke kritisk og man kan anvende temperaturer fra -10° til +60°C. Reaksjonstiden er avhengig av reaksjonstemperaturen, men vanligvis vil tidsrom fra 4 timer til 1 døgn være tilstrekkelig. Any known ether can be used in this reaction. Suitable ethers include diethyl ether, tetrahydropyran, tetrahydrofuran and dimethoxyethane. The reaction temperature is not critical and temperatures from -10° to +60°C can be used. The reaction time depends on the reaction temperature, but usually a period of 4 hours to 1 day will be sufficient.
Forbindelsen med formel II kan så utskilles fra reaksjonsblandingen med vanlig kjent teknikk.. F.eks. kan reaksjonsblandingen fortynnes med vann eller blandes med is og ekstraheres med dietyleter eller lignende oppløsningsmidler. Den organiske fase kan så utskilles, tørkes og fordampes til tørrhet, hvoretter residuet ut-krystalliseres fra aceton-héksan til forbindelsen med formel II. Kromatografi kan også brukes for å rense og/eller isolere forbindelsen med formel II. The compound with formula II can then be separated from the reaction mixture using conventional techniques. E.g. the reaction mixture can be diluted with water or mixed with ice and extracted with diethyl ether or similar solvents. The organic phase can then be separated, dried and evaporated to dryness, after which the residue is crystallized from acetone-hexane to give the compound of formula II. Chromatography can also be used to purify and/or isolate the compound of formula II.
Den fjerde ovenfor angitte alternative fremgangsmåte kan angis ved følgende reaksjon: The fourth alternative method indicated above can be indicated by the following reaction:
Forbindelser med formel II kan fremstilles ved å omsette forbindelser med formel le med hydrogen i nærvær av en hydrogeneringskatalysator i et inert organisk oppløsningsmiddel. Compounds of formula II can be prepared by reacting compounds of formula 1e with hydrogen in the presence of a hydrogenation catalyst in an inert organic solvent.
Egnede hydrogeneringskatalysatorer for denne reaksjon innbefatter palladium, platina, ruthenium, rhodium eller triklortris-(metylpropylfenylfosfin)rhodium. Suitable hydrogenation catalysts for this reaction include palladium, platinum, ruthenium, rhodium or trichlorotris-(methylpropylphenylphosphine)rhodium.
Reaksjonen utføres i et inert organisk oppløsningsmiddel, f.eks. en flytende alkanol, slik som etanol og metanol, estere såSom etylacetat, etere såsom dietyleter, tetrahydrofuran, tetrahydropyran og dimetoksyetan, samt hydrokarboner såsom n-heksan, benzen, toluen og xylen. Halogenerte hydrokarboner er ikke foretrukket ettersom disse vanligvis deaktiverer katalysatoren. The reaction is carried out in an inert organic solvent, e.g. a liquid alkanol, such as ethanol and methanol, esters such as ethyl acetate, ethers such as diethyl ether, tetrahydrofuran, tetrahydropyran and dimethoxyethane, and hydrocarbons such as n-hexane, benzene, toluene and xylene. Halogenated hydrocarbons are not preferred as these usually deactivate the catalyst.
Reaksjonen kan utføres i et surt, nøytralt eller basisk mil-jø. Fortrinnsvis bør reaksjonen utføres under nøytrale betingelser. The reaction can be carried out in an acidic, neutral or basic environment. Preferably, the reaction should be carried out under neutral conditions.
Temperaturen ved hvilken reaksjonen utføres er ikke kritisk. The temperature at which the reaction is carried out is not critical.
P.eks. kan reaksjonen utføres ved temperaturer fra 0°C til oppløs-ningsmidlets koketemperatur eller endog høyere (hvis systemet er under trykk). Reaksjonen utføres inntil hydrogeneringen er fullstendig, vanligvis vil dette ta fra 15 minutter til 48 timer. Normalt vil 2 timer være tilstrekkelig. E.g. the reaction can be carried out at temperatures from 0°C to the solvent's boiling temperature or even higher (if the system is under pressure). The reaction is carried out until the hydrogenation is complete, usually this will take from 15 minutes to 48 hours. Normally 2 hours will be sufficient.
Forbindelsen med formel II kan så utskilles fra reaksjonsblandingen ved vanlig kjent teknikk, f.eks. ved å filtrere det hele for å fjerne katalysatoren, hvoretter oppløsningsmidlet fordampes. The compound of formula II can then be separated from the reaction mixture by conventional techniques, e.g. by filtering the whole to remove the catalyst, after which the solvent is evaporated.
Forbindelsene med formel le kan fremstilles på flere måter; The compounds of formula 1e can be prepared in several ways;
således kan 2-(6-metoksy-2-naftyl)akrylsyre fremstilles ved å behandle en 6-metoksy-2-naftyleddiksyreester med formaldehyd eller paraformaldehyd og et alkalimetallalkoksyd i dimetylsulfoksyd fulgt av en surgjøring av reaksjonsblandingen. Den fremstilte 2-(6-met-oksy-2-naftyl)akrylsyre blir deretter redusert med litiumaluminiumhydrid i en eter, f.eks. dietyleter, hvorved man får fremstilt den tilsvarende 2-(6-metoksy-2-naftyl)-2-propen-l-ol med formel le. thus, 2-(6-methoxy-2-naphthyl)acrylic acid can be prepared by treating a 6-methoxy-2-naphthylacetic acid ester with formaldehyde or paraformaldehyde and an alkali metal alkoxide in dimethyl sulfoxide followed by acidification of the reaction mixture. The 2-(6-methoxy-2-naphthyl)acrylic acid produced is then reduced with lithium aluminum hydride in an ether, e.g. diethyl ether, whereby the corresponding 2-(6-methoxy-2-naphthyl)-2-propen-1-ol of formula le is produced.
Den femte ovenfor angitte alternative fremgangsmåte kan angis ved følgende formler: The fifth alternative method indicated above can be expressed by the following formulas:
Forbindelsen med formel II kan fremstilles ved å omsette The compound of formula II can be prepared by reacting
forbindelsen med formel If med diboran i en eter. the compound of formula If with diborane in an ether.
Eteroppløsningsmidlet for denne reaksjon er ikke kritisk. Egnede etere innbefatter dietyleter, dimetoksyetan, tetrahydrofuran og tetrahydropyran. Man bør anvende minst 1 mol ekvivalent, fortrinnsvis minst 2 mol ekvivalenter diboran i reaksjonsblandingen. The ether solvent for this reaction is not critical. Suitable ethers include diethyl ether, dimethoxyethane, tetrahydrofuran and tetrahydropyran. One should use at least 1 mol equivalent, preferably at least 2 mol equivalents of diborane in the reaction mixture.
Temperaturen for denne reaksjon er ikke kritisk og man kan anvende temperaturer fra -10° til +30°C, fortrinnsvis 0° til 20°C. Reaksjonstiden er avhengig av temperaturen, men vanligvis vil tidsrom fra 1 til 12 timer være tilstrekkelig. The temperature for this reaction is not critical and one can use temperatures from -10° to +30°C, preferably 0° to 20°C. The reaction time depends on the temperature, but usually a period of 1 to 12 hours will be sufficient.
Overskuddet av diboran blir fortrinnsvis dekomponert før man utskiller produktet fra reaksjonsblandingen. Dette kan f.eks. utføres ved å tilsette enhver organisk eller uorganisk syre til reaksjonsblandingen. Eddiksyre er f.eks. meget godt egnet. The excess diborane is preferably decomposed before separating the product from the reaction mixture. This can e.g. is carried out by adding any organic or inorganic acid to the reaction mixture. Acetic acid is e.g. very well suited.
Forbindelsen med formel II blir så utskilt fra reaksjonsblandingen ved vanlig kjent teknikk. F.eks. kan reaksjonsblandingen fortynnes med vann og ekstraheres med eter, hvoretter eterfasen utskilles og fordampes til tørrhet, noe som gir forbindelsen med formel II. Kromatografi kan også anvendes for å rense og/eller isolere forbindelsen med formel II. The compound of formula II is then separated from the reaction mixture by conventional techniques. E.g. the reaction mixture can be diluted with water and extracted with ether, after which the ether phase is separated and evaporated to dryness, giving the compound of formula II. Chromatography can also be used to purify and/or isolate the compound of formula II.
Forbindelsen med formel II har anti-inflammatorisk,- smer-testillende og anti-pyretisk aktivitet og kan følgelig anvendes for behandling av inflammasjon, smerter og lignende lidelser hos pattedyr. F.eks. kan man ved hjelp av nevnte forbindelse behandle inflammatoriske tilstander i muskelskjelettsystemet, leddene eller andre typer vev. Foreliggende forbindelse kan følgelig brukes ved å behandle tilstander karakterisert ved en inflammasjon, f.eks. reumatisme, hjernerystelse, arthritis, benbrudd, posttraumatiske tilstander etc. The compound of formula II has anti-inflammatory, analgesic and anti-pyretic activity and can consequently be used for the treatment of inflammation, pain and similar disorders in mammals. E.g. can one use said compound to treat inflammatory conditions in the musculoskeletal system, joints or other types of tissue. The present compound can therefore be used to treat conditions characterized by inflammation, e.g. rheumatism, concussion, arthritis, broken bones, post-traumatic conditions etc.
Utgangsforbindelser som kan anvendes i foreliggende fremgangsmåte oppnås hensiktsmessig som følger: A. En oppløsning av 12,5 g 1-brom-l-(6-metoksy-2-naf-tyl)-etan i 100 ml tetrahydrofuran ble langsomt tilsatt en blanding av 10 g magnesiumpulver i 100 ml tetrahydrofuran ved'45°C Etterat tilsetningen var fullstendig, ble blandingen rørt i 15 minutter, Starting compounds that can be used in the present process are conveniently obtained as follows: A. A solution of 12.5 g of 1-bromo-1-(6-methoxy-2-naphthyl)-ethane in 100 ml of tetrahydrofuran was slowly added to a mixture of 10 g of magnesium powder in 100 ml of tetrahydrofuran at 45°C. After the addition was complete, the mixture was stirred for 15 minutes,
og oppløsningen utskilt fra overskuddet av metall, hvorved man fikk fremstilt 1-(6-metoksy-2-naftyl)-1-etyl-magnesiumbromid. and the solution separated from the excess of metal, whereby 1-(6-methoxy-2-naphthyl)-1-ethylmagnesium bromide was produced.
Ved å anvende samme fremgangsmåte, men ved å bruke By applying the same procedure, but by using
litium eller sinkpulver- istedenfor magnesiumpulver, får man fremstilt l-(6-metoksy-2-naftyl)-l-etyl-litium og sink henholdsvis. lithium or zinc powder - instead of magnesium powder, l-(6-methoxy-2-naphthyl)-l-ethyl-lithium and zinc respectively are produced.
Den ovennevnte oppløsning (etter utskillelsen av metall-overskuddet) blandes med 7 g kadmiumklorid, og blandingen røres i 30 minutter, noe som gir en oppløsning inneholdende 1-(6-metoksy-2-naftyl)-1-etyl kadmium. The above solution (after separation of the excess metal) is mixed with 7 g of cadmium chloride, and the mixture is stirred for 30 minutes, which gives a solution containing 1-(6-methoxy-2-naphthyl)-1-ethyl cadmium.
Ved å gjenta denne fremgangsmåte, men ved å anvende fin-fordelt natrium eller kalium istedenfor kadmiumklorid, får man fremstilt l-(6-metoksy-2-naftyl)-1-etyl natrium eller kalium henholdsvis. By repeating this procedure, but by using finely divided sodium or potassium instead of cadmium chloride, 1-(6-methoxy-2-naphthyl)-1-ethyl sodium or potassium respectively is produced.
B. Ved å anvende følgende fremgangsmåte fikk man fremstilt 2-acetyl-6-metoksynaftalen . Nitrobenzen (14.000 ml) og 2-metdcsy-naftalen (2000 g) ble blandet under nitrogen og avkjølt til temperaturer fra 0 til 5°C. Oppløsningen ble så tilsatt aluminiumtriklorid (2600 g) i nitrobenzen (20.000 ml) avkjølt til 0 til 5°C. Acetyl-klorid (1300 g) ble tilsatt blandingen i løpet av 30 til 40 minutter samtidig som temperaturen ble holdt under 25°C. Etterat acety'1-kloridtilsetningen var fullstendig, ble blandingen oppvarmet til 35°C og holdt på denne temperatur i 10 timer. B. By using the following procedure, 2-acetyl-6-methoxynaphthalene was produced. Nitrobenzene (14,000 mL) and 2-methoxynaphthalene (2000 g) were mixed under nitrogen and cooled to temperatures from 0 to 5°C. To the solution was then added aluminum trichloride (2600 g) in nitrobenzene (20,000 ml) cooled to 0 to 5°C. Acetyl chloride (1300 g) was added to the mixture over 30 to 40 minutes while maintaining the temperature below 25°C. After the acetyl chloride addition was complete, the mixture was heated to 35°C and held at this temperature for 10 hours.
Blandingen ble gjentatte ganger vasket med vann inneholdende saltsyre for å fjerne organiske urenheter fra nitrobenzen-laget, hvoretter dette under vakuum ble konsentrert til en tung sirup. 2-acdtyl-6-metoksynaftalen-produktet ble utskilt ved å tilsette metanol og deretter vann, filtrere, vaske, tørke og krystal-lisere fra cykloheksan. C. En blanding'av dimetylsulfoksyd (48OO ml) og tetrahydrofuran (400 ml) ble renset med nitrogen og avkjølt til 10-15°C. Blandingen ble så tilsatt natriummetoksyd (500 g) og trimetylsulfo-niumiodid (1300 g) . Samtidig som temperaturen ble holdt på 10-15°C, ble en oppløsning av 2-acetyl-6-metoksynaftalen (100 g) i en blanding av dimetylsulfoksyd (2400 ml) og tetrahydrofuran (920 ml) tilsatt iløpet av Jd minutter. Etterat temperaturen var holdt på fra 10-15°C i ytterligere 15 minutter, ble reaksjonsblandingen fortynnet til et totalt volum på-50-000 ml med kaldt vann, hvoretter det hele ble filtrert, filterkaken vasket med vann inntil nøytralitet. Produktet 2-(6-metoksy-2-naftyl)propylenoksyd ble tørket ved 50°C. The mixture was repeatedly washed with water containing hydrochloric acid to remove organic impurities from the nitrobenzene layer, after which this was concentrated under vacuum to a heavy syrup. The 2-acdtyl-6-methoxynaphthalene product was isolated by adding methanol and then water, filtering, washing, drying and crystallizing from cyclohexane. C. A mixture of dimethyl sulfoxide (4800 mL) and tetrahydrofuran (400 mL) was purged with nitrogen and cooled to 10-15°C. Sodium methoxide (500 g) and trimethylsulfonium iodide (1300 g) were then added to the mixture. While maintaining the temperature at 10-15°C, a solution of 2-acetyl-6-methoxynaphthalene (100 g) in a mixture of dimethylsulfoxide (2400 ml) and tetrahydrofuran (920 ml) was added over Jd minutes. After maintaining the temperature at 10-15°C for a further 15 minutes, the reaction mixture was diluted to a total volume of -50-000 ml with cold water, after which the whole was filtered, the filter cake washed with water until neutrality. The product 2-(6-methoxy-2-naphthyl)propylene oxide was dried at 50°C.
Eksempel 1.. Example 1..
En oppløsning av 10 g 6-metoksy-2-(2-properiyl)-naftalen i 100 ml eter ble behandlet med en oppløsning av diboran i tetrahydrofuran inntil en analyse ved tynnsjiktkromatografien indikerte at reaksjonen var fullstendig. Bladningen ble så ved 0°C behandlet med 50 ml 3~n vandig natriumhydroksyd og 20 ml 30^-ig hydrogenperoksyd tilsatt i porsjoner iløpet av 30 minutter. Etter omrøring i 4 timer ved & <. 00C. ble vann tilsatt reaksjonsblandingen, og produktet ekstrahert med eter. Eterfasen ble fordampet til tørrhet, hvorved man fikk fremstilt 2-(6-metoksy-2-naftyl)-1-propanol, som ble omkrystallisert fra aceton-heksan. A solution of 10 g of 6-methoxy-2-(2-properyl)-naphthalene in 100 ml of ether was treated with a solution of diborane in tetrahydrofuran until analysis by thin layer chromatography indicated that the reaction was complete. The leaf was then treated at 0°C with 50 ml of 3% aqueous sodium hydroxide and 20 ml of 30% hydrogen peroxide added in portions over 30 minutes. After stirring for 4 hours at & <. 00C. water was added to the reaction mixture, and the product was extracted with ether. The ether phase was evaporated to dryness, whereby 2-(6-methoxy-2-naphthyl)-1-propanol was produced, which was recrystallized from acetone-hexane.
Eksempel 2. Example 2.
En blanding av 22 g 2-(6-metoksy-2-naftyl)propanol, 30 g fthalsyreanhydrid og 500 ml pyridin ble omrørt i 6 timer ved romtemperatur. Den resulterende blanding ble så fortynnet med vann og ekstrahert med metylenklorid. De samlede ekstrakter ble vasket med vann, vandig 0,1-n saltsyre og med vann til nøytralitet, tørket over natriumsulfat og fordampet til tørrhet, hvorved man fikk fthalsyreesteren som ble utkrystallisert fra vandig etanol. A mixture of 22 g of 2-(6-methoxy-2-naphthyl)propanol, 30 g of phthalic anhydride and 500 ml of pyridine was stirred for 6 hours at room temperature. The resulting mixture was then diluted with water and extracted with methylene chloride. The combined extracts were washed with water, aqueous 0.1-n hydrochloric acid and with water to neutrality, dried over sodium sulfate and evaporated to dryness, whereby the phthalic acid ester was obtained which was crystallized from aqueous ethanol.
Denne ester (36 g), 29 g cinchonidin og 500 ml metanol ble omrørt i 2 timer. Blandingen ble så hensatt inntil utkrystalli-sasjonen var fullstendig. Krystallene ble fjernet ved filtrering og vasket med metanol (filtratet og vaskeoppløsningen ble oppsamlet). Krystallene ble så omkrystallisert fra metanol, filtrert, vasket og tørket. De rene krystaller ble tilsatt 600 ml 0,2-n saltsyre og den resulterende blanding omrørt i 2 timer og så ekstrahert med dietyleter. Ekstraktene ble slått sammen, vasket med vann til nøytra-litet, tørket over natriumsulfat og fordampet. This ester (36 g), 29 g of cinchonidine and 500 ml of methanol were stirred for 2 hours. The mixture was then allowed to stand until crystallization was complete. The crystals were removed by filtration and washed with methanol (the filtrate and washing solution were collected). The crystals were then recrystallized from methanol, filtered, washed and dried. The pure crystals were added to 600 ml of 0.2-N hydrochloric acid and the resulting mixture stirred for 2 hours and then extracted with diethyl ether. The extracts were combined, washed with water until neutral, dried over sodium sulfate and evaporated.
Det resulterende residuum ble tilsatt en blanding av The resulting residue was added to a mixture of
5g natriumhydroksyd, 250 ml vann og 250 ml tetrahydrofuran. Etter henstand i 2 timer ved 23°C ble blandingen.ekstrahert med metylen-, klorid. De samlede ekstrakter ble vasket med vandig syré og deretter med vann til nøytralitet, tørket over natriumsulfat og fordampet, hvorved man fikk 1 2-(6-metoksy-2-haftyl) -prbpanol.' 5g sodium hydroxide, 250 ml water and 250 ml tetrahydrofuran. After standing for 2 hours at 23°C, the mixture was extracted with methylene chloride. The combined extracts were washed with aqueous acid and then with water to neutrality, dried over sodium sulfate and evaporated to give 1 2-(6-methoxy-2-haphtyl)-prbanol.
De samlede filtrater og vaskeoppløsninger ble fordampet og residuet behandlet som beskrevet ovenfor for derved å kløve cinchonidinsaltet og hydrolysere esteren, hvorved man fikk 1 2-(6-metoksy-2-naftyl)propionsyre. The combined filtrates and washing solutions were evaporated and the residue treated as described above to thereby cleave the cinchonidine salt and hydrolyze the ester, whereby 1 2-(6-methoxy-2-naphthyl)propionic acid was obtained.
Eksempel 3- Example 3-
5 g paraformaldehyd ble tilsatt en oppløsning av 0,1 ekvivalenter 1-(6-metoksy-2-naftyl)-1-etyl magnesiumbromid i 20 ml tetrahydrofuran og blandingen ble oppvarmet under tilbakeløp i 24 timer. Reaksjonsblandingen ble så fordampet til tørrhet og surgjort med et overskudd av fortynnet saltsyre og så fortynnet med vann. 2-(6-metoksy-2-naftyl)-1-propanol ble så utfelt fra blandingen og fjernet ved filtrering og krystallisert fra aceton-heksan. To 5 g of paraformaldehyde was added a solution of 0.1 equivalents of 1-(6-methoxy-2-naphthyl)-1-ethyl magnesium bromide in 20 ml of tetrahydrofuran and the mixture was heated under reflux for 24 hours. The reaction mixture was then evaporated to dryness and acidified with an excess of dilute hydrochloric acid and then diluted with water. 2-(6-Methoxy-2-naphthyl)-1-propanol was then precipitated from the mixture and removed by filtration and crystallized from acetone-hexane.
Ved å gjenta denne fremgangsmåte, men ved å erstatte 1-(6-metoksy-2-naftyl)-1-etyl magnesiumbromid med det tilsvarende 1-(6-metoksy-2-naftyl)-1-etyl magnesiumiodid, 1-(6-metoksy-2-naftyl)-1-etyl magnesiumklorid, 1-(6-metoksy-2-naftyl)-1-etyl litium, 1-(6-metoksy-2-naftyl)-1-etyl-sink, 1-(6-metoksy-2-naftyl)-1-etyl kadmium, 1-(6-metoksy-2-naftyl)- 1-etyl natrium og 1-(6-metoksy-2-naftyl)-1-etyl-kalium, så får man fremstilt den tilsvarende forbindelse, nemlig 2-(6-metoksy-2-naftyl)-1-propanol. By repeating this procedure, but replacing 1-(6-methoxy-2-naphthyl)-1-ethyl magnesium bromide with the corresponding 1-(6-methoxy-2-naphthyl)-1-ethyl magnesium iodide, 1-(6 -methoxy-2-naphthyl)-1-ethyl magnesium chloride, 1-(6-methoxy-2-naphthyl)-1-ethyl lithium, 1-(6-methoxy-2-naphthyl)-1-ethyl zinc, 1- (6-methoxy-2-naphthyl)-1-ethyl cadmium, 1-(6-methoxy-2-naphthyl)-1-ethyl sodium and 1-(6-methoxy-2-naphthyl)-1-ethyl potassium, then the corresponding compound is produced, namely 2-(6-methoxy-2-naphthyl)-1-propanol.
Eksempel 4. Example 4.
En oppløsning av l8 g 2-(6-metoksy-2-naftyl)-propylenok-syd i 50° ml dietyleter ble ved 0°C behandlet med 14 g aluminiumklorid og 200 ml av l-n diboranoppløsning i tetrahydrofuran. Blandingen ble hensatt i 24 timer ved 20°C. Den ble så blandet med is og ekstrahert med dietyleter. Den•organiske fase ble fordampet til tørrhet og residuet rekrystallisert fra aceton-heksan til 2-(6-metoksy-2-naftyl)-1-propanol. A solution of 18 g of 2-(6-methoxy-2-naphthyl)-propylene oxide in 50 ml of diethyl ether was treated at 0°C with 14 g of aluminum chloride and 200 ml of a 1-n diborane solution in tetrahydrofuran. The mixture was left for 24 hours at 20°C. It was then mixed with ice and extracted with diethyl ether. The organic phase was evaporated to dryness and the residue recrystallized from acetone-hexane to 2-(6-methoxy-2-naphthyl)-1-propanol.
Eksempel 5. Example 5.
Ved å gjenta fremgangsmåten fra Eksempel 4» men ved å erstatte diboran med en ekvivalent mengde litiumaluminiumhydrid, natriumborhydrid, kaliumborhydrid eller litiumborhydrid, gir i hvert enkelt tilfelle 2-(6-metoksy-2-naftyl)-1-propanol. By repeating the procedure from Example 4" but by replacing the diborane with an equivalent amount of lithium aluminum hydride, sodium borohydride, potassium borohydride or lithium borohydride, gives in each case 2-(6-methoxy-2-naphthyl)-1-propanol.
Eksempel 6. Example 6.
Ved å gjenta fremgangsmåten fra Eksempel 4> men ved å erstatte aluminiumklorid med bortriklorid, bortrifluorid, bortrifluorid-dietyleter, aluminiumbromid, .bortribromid, gir i hvert enkelt tilfelle 2-(6-metoksy-2-naftyl)-1-propanol. By repeating the procedure from Example 4> but by replacing aluminum chloride with boron trichloride, boron trifluoride, boron trifluoride-diethyl ether, aluminum bromide, boron tribromide, in each case 2-(6-methoxy-2-naphthyl)-1-propanol is given.
Eksempel 7- Example 7-
En oppløsning av 10 g 2-(6-metoksy-2-naftyl)-2-propen-l-ol i 200 ml"etylacetat inneholdende 0,5 g av en 5$ palladium-på-karbon-katalysator, ble i 2 timer ved romtemperatur hydrogenert, ■ • Filtrering av reaksjonsblandingen og en fordamping av oppløsnings-midlet fra filtratet, gir 2-(6-metoksy-2-naftyl)-1-propanol som ble omkrystallisert fra aceton-heksan. A solution of 10 g of 2-(6-methoxy-2-naphthyl)-2-propen-1-ol in 200 ml of ethyl acetate containing 0.5 g of a 5$ palladium-on-carbon catalyst was for 2 hours hydrogenated at room temperature, ■ • Filtration of the reaction mixture and evaporation of the solvent from the filtrate gives 2-(6-methoxy-2-naphthyl)-1-propanol which was recrystallized from acetone-hexane.
Eksempel 8. Example 8.
En oppløsning av 5 g 2-(6-metoksy-2-naftyl)-akrylsyre A solution of 5 g of 2-(6-methoxy-2-naphthyl)-acrylic acid
i 20 ml tetrahydrofuran ved 0°C ble behandlet med 50 ml l-n diboran i tetrahydrofuran. Etter 4 timer ble overskuddet av diboran dekomponert ved å tilsette eddiksyre inntil hydrogenutskillelsen var in 20 ml of tetrahydrofuran at 0°C was treated with 50 ml of 1-n diborane in tetrahydrofuran. After 4 hours, the excess of diborane was decomposed by adding acetic acid until the evolution of hydrogen was
stoppet opp. Reaksjonsblandingen ble så blandet med vann og ekstrahert med eter, eterfasen fjernet og fordampet til tørrhet, hvorved man fikk fremstilt 2-(6-metoksy-2-naftyl)-l-propanol. stopped. The reaction mixture was then mixed with water and extracted with ether, the ether phase removed and evaporated to dryness, whereby 2-(6-methoxy-2-naphthyl)-1-propanol was produced.
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US86245469A | 1969-09-30 | 1969-09-30 | |
US86247169A | 1969-09-30 | 1969-09-30 | |
US86245569A | 1969-09-30 | 1969-09-30 | |
US86245369A | 1969-09-30 | 1969-09-30 | |
US86250169A | 1969-09-30 | 1969-09-30 | |
US86249869A | 1969-09-30 | 1969-09-30 | |
US86247569A | 1969-09-30 | 1969-09-30 |
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CH543467A (en) | 1973-10-31 |
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DK145338B (en) | 1982-11-01 |
FR2068539B1 (en) | 1974-02-22 |
CH547248A (en) | 1974-03-29 |
FI50620C (en) | 1976-05-10 |
DK145338C (en) | 1983-03-21 |
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