SK29099A3 - Process for the preparation of fluoxetine - Google Patents
Process for the preparation of fluoxetine Download PDFInfo
- Publication number
- SK29099A3 SK29099A3 SK290-99A SK29099A SK29099A3 SK 29099 A3 SK29099 A3 SK 29099A3 SK 29099 A SK29099 A SK 29099A SK 29099 A3 SK29099 A3 SK 29099A3
- Authority
- SK
- Slovakia
- Prior art keywords
- formula
- compound
- reaction
- phenyl
- amine
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 39
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 title description 17
- 229960002464 fluoxetine Drugs 0.000 title description 17
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims abstract description 54
- 150000001875 compounds Chemical class 0.000 claims abstract description 38
- 238000006243 chemical reaction Methods 0.000 claims abstract description 33
- 239000011541 reaction mixture Substances 0.000 claims abstract description 31
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims abstract description 26
- 239000008096 xylene Substances 0.000 claims abstract description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000002253 acid Substances 0.000 claims abstract description 19
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- 239000000203 mixture Substances 0.000 claims abstract description 14
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 claims abstract description 13
- 238000009835 boiling Methods 0.000 claims abstract description 12
- 230000007062 hydrolysis Effects 0.000 claims abstract description 12
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 12
- 239000012074 organic phase Substances 0.000 claims abstract description 12
- 239000002585 base Substances 0.000 claims abstract description 11
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims abstract description 10
- 150000003673 urethanes Chemical class 0.000 claims abstract description 10
- 239000006227 byproduct Substances 0.000 claims abstract description 7
- RTHCYVBBDHJXIQ-UHFFFAOYSA-N N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine Chemical compound C=1C=CC=CC=1C(CCNC)OC1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-UHFFFAOYSA-N 0.000 claims abstract description 6
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 6
- 238000006114 decarboxylation reaction Methods 0.000 claims abstract description 5
- 150000002484 inorganic compounds Chemical class 0.000 claims abstract description 4
- 229910010272 inorganic material Inorganic materials 0.000 claims abstract description 4
- QUFZVVNFYXEIAK-UHFFFAOYSA-N n,n-dimethyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine Chemical compound C=1C=CC=CC=1C(CCN(C)C)OC1=CC=C(C(F)(F)F)C=C1 QUFZVVNFYXEIAK-UHFFFAOYSA-N 0.000 claims abstract description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 36
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 27
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 18
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 16
- 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 claims description 11
- 150000007522 mineralic acids Chemical class 0.000 claims description 5
- 229910001854 alkali hydroxide Inorganic materials 0.000 abstract description 2
- 230000001430 anti-depressive effect Effects 0.000 abstract description 2
- 239000000935 antidepressant agent Substances 0.000 abstract description 2
- 229940005513 antidepressants Drugs 0.000 abstract description 2
- AUXZZUAGZGDPRQ-UHFFFAOYSA-N ethyl n-methyl-n-[3-phenyl-3-[4-(trifluoromethyl)phenoxy]propyl]carbamate Chemical compound C=1C=CC=CC=1C(CCN(C)C(=O)OCC)OC1=CC=C(C(F)(F)F)C=C1 AUXZZUAGZGDPRQ-UHFFFAOYSA-N 0.000 abstract description 2
- 238000011109 contamination Methods 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- 239000002609 medium Substances 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 230000035484 reaction time Effects 0.000 description 8
- 239000000356 contaminant Substances 0.000 description 7
- -1 3-hydroxy-3-phenyl-propyl Chemical group 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 6
- BAYGVMXZJBFEMB-UHFFFAOYSA-N 4-(trifluoromethyl)phenol Chemical compound OC1=CC=C(C(F)(F)F)C=C1 BAYGVMXZJBFEMB-UHFFFAOYSA-N 0.000 description 5
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- QULYNCCPRWKEMF-UHFFFAOYSA-N parachlorobenzotrifluoride Chemical compound FC(F)(F)C1=CC=C(Cl)C=C1 QULYNCCPRWKEMF-UHFFFAOYSA-N 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- GIYXAJPCNFJEHY-UHFFFAOYSA-N N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]-1-propanamine hydrochloride (1:1) Chemical compound Cl.C=1C=CC=CC=1C(CCNC)OC1=CC=C(C(F)(F)F)C=C1 GIYXAJPCNFJEHY-UHFFFAOYSA-N 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- 239000007789 gas Substances 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 239000012535 impurity Substances 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- IVSZLXZYQVIEFR-UHFFFAOYSA-N m-xylene Chemical compound CC1=CC=CC(C)=C1 IVSZLXZYQVIEFR-UHFFFAOYSA-N 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- XXSDCGNHLFVSET-UHFFFAOYSA-N 3-(methylamino)-1-phenylpropan-1-ol Chemical compound CNCCC(O)C1=CC=CC=C1 XXSDCGNHLFVSET-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 238000009776 industrial production Methods 0.000 description 3
- 229940050176 methyl chloride Drugs 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 150000003891 oxalate salts Chemical class 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- URLKBWYHVLBVBO-UHFFFAOYSA-N Para-Xylene Chemical group CC1=CC=C(C)C=C1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- AKZWRTCWNXHHFR-PDIZUQLASA-N [(3S)-oxolan-3-yl] N-[(2S,3S)-4-[(5S)-5-benzyl-3-[(2R)-2-carbamoyloxy-2,3-dihydro-1H-inden-1-yl]-4-oxo-3H-pyrrol-5-yl]-3-hydroxy-1-phenylbutan-2-yl]carbamate Chemical compound NC(=O)O[C@@H]1Cc2ccccc2C1C1C=N[C@](C[C@H](O)[C@H](Cc2ccccc2)NC(=O)O[C@H]2CCOC2)(Cc2ccccc2)C1=O AKZWRTCWNXHHFR-PDIZUQLASA-N 0.000 description 2
- 239000011260 aqueous acid Substances 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000017858 demethylation Effects 0.000 description 2
- 238000010520 demethylation reaction Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 229960000389 fluoxetine hydrochloride Drugs 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 150000003738 xylenes Chemical class 0.000 description 2
- USVVENVKYJZFMW-ONEGZZNKSA-N (e)-carboxyiminocarbamic acid Chemical compound OC(=O)\N=N\C(O)=O USVVENVKYJZFMW-ONEGZZNKSA-N 0.000 description 1
- XVMIKRZPDSXBTP-UHFFFAOYSA-N 1,3-dibromobutan-2-one Chemical compound CC(Br)C(=O)CBr XVMIKRZPDSXBTP-UHFFFAOYSA-N 0.000 description 1
- DGRVQOKCSKDWIH-UHFFFAOYSA-N 1-chloro-2-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1Cl DGRVQOKCSKDWIH-UHFFFAOYSA-N 0.000 description 1
- HQROXDLWVGFPDE-UHFFFAOYSA-N 1-chloro-4-nitro-2-(trifluoromethyl)benzene Chemical compound [O-][N+](=O)C1=CC=C(Cl)C(C(F)(F)F)=C1 HQROXDLWVGFPDE-UHFFFAOYSA-N 0.000 description 1
- GBQRSEVKSZQWFF-UHFFFAOYSA-N 1h-indole-2,4-dicarboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)=CC2=C1C(O)=O GBQRSEVKSZQWFF-UHFFFAOYSA-N 0.000 description 1
- WXXRCNKKYCNYFF-UHFFFAOYSA-N 1h-indole-2,6-dicarboxylic acid Chemical compound C1=C(C(O)=O)C=C2NC(C(=O)O)=CC2=C1 WXXRCNKKYCNYFF-UHFFFAOYSA-N 0.000 description 1
- VELGOYBSKBKQFF-UHFFFAOYSA-N 3-(dimethylamino)-1-phenylpropan-1-ol Chemical compound CN(C)CCC(O)C1=CC=CC=C1 VELGOYBSKBKQFF-UHFFFAOYSA-N 0.000 description 1
- QMNXJNURJISYMS-UHFFFAOYSA-N 3-(dimethylamino)-1-phenylpropan-1-one Chemical compound CN(C)CCC(=O)C1=CC=CC=C1 QMNXJNURJISYMS-UHFFFAOYSA-N 0.000 description 1
- HOJWFVSHZMXLAP-UHFFFAOYSA-N 3-[benzyl(methyl)amino]-1-phenylpropan-1-ol Chemical compound C=1C=CC=CC=1CN(C)CCC(O)C1=CC=CC=C1 HOJWFVSHZMXLAP-UHFFFAOYSA-N 0.000 description 1
- LNCWFHRJTAQGBG-UHFFFAOYSA-N 3-[benzyl(methyl)amino]-1-phenylpropan-1-one Chemical compound C=1C=CC=CC=1CN(C)CCC(=O)C1=CC=CC=C1 LNCWFHRJTAQGBG-UHFFFAOYSA-N 0.000 description 1
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
- CDWGDLKZKCYUFO-UHFFFAOYSA-N 6-(trifluoromethyl)-1h-indole-2-carboxylic acid Chemical compound C1=C(C(F)(F)F)C=C2NC(C(=O)O)=CC2=C1 CDWGDLKZKCYUFO-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- BMTAFVWTTFSTOG-UHFFFAOYSA-N Butylate Chemical compound CCSC(=O)N(CC(C)C)CC(C)C BMTAFVWTTFSTOG-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- GKKZMYDNDDMXSE-UHFFFAOYSA-N Ethyl 3-oxo-3-phenylpropanoate Chemical compound CCOC(=O)CC(=O)C1=CC=CC=C1 GKKZMYDNDDMXSE-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- PODSRQPTUWGSQX-UHFFFAOYSA-N [3-[acetyl(methyl)amino]-1-phenylpropyl] methanesulfonate Chemical compound CC(=O)N(C)CCC(OS(C)(=O)=O)C1=CC=CC=C1 PODSRQPTUWGSQX-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- DVIBDQWVFHDBOP-UHFFFAOYSA-N ethyl 3-hydroxy-3-phenylpropanoate Chemical compound CCOC(=O)CC(O)C1=CC=CC=C1 DVIBDQWVFHDBOP-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- XJAKKLMDUCLYDF-UHFFFAOYSA-N methyl n-methyl-n-[3-phenyl-3-[4-(trifluoromethyl)phenoxy]propyl]carbamate Chemical compound C=1C=CC=CC=1C(CCN(C)C(=O)OC)OC1=CC=C(C(F)(F)F)C=C1 XJAKKLMDUCLYDF-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical class CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000013275 serotonin uptake Effects 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000005979 thermal decomposition reaction Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/08—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C217/48—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated and containing rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU9602469A HU226690B1 (en) | 1996-09-10 | 1996-09-10 | Process for producing fluoxetin |
| PCT/HU1997/000050 WO1998011054A1 (en) | 1996-09-10 | 1997-09-10 | Process for the preparation of fluoxetine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SK29099A3 true SK29099A3 (en) | 1999-08-06 |
Family
ID=89994255
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK290-99A SK29099A3 (en) | 1996-09-10 | 1997-09-10 | Process for the preparation of fluoxetine |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP0929514A1 (cs) |
| AU (1) | AU4468997A (cs) |
| CZ (1) | CZ75299A3 (cs) |
| HU (1) | HU226690B1 (cs) |
| PL (1) | PL332141A1 (cs) |
| SK (1) | SK29099A3 (cs) |
| WO (1) | WO1998011054A1 (cs) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6025517A (en) * | 1998-08-03 | 2000-02-15 | Sepracor Inc. | Fluoxetine process from benzoylacetonitrile |
| US6258853B1 (en) | 2001-01-31 | 2001-07-10 | Grayson Walker Stowell | Form a of fluoxetine hydrochloride |
| US6310250B1 (en) | 2001-01-31 | 2001-10-30 | Grayson Walker Stowell | Form A of fluoxetine hydrochloride |
| US6316672B1 (en) | 2001-01-31 | 2001-11-13 | Grayson Walker Stowell | Form a of fluoxetine hydrochloride |
| US6310251B1 (en) | 2001-01-31 | 2001-10-30 | Grayson Walker Stowell | Form a of fluoxetine hydrochloride |
| US6313350B1 (en) | 2001-01-31 | 2001-11-06 | Grayson Walker Stowell | Form a of fluoxetine hydrochloride |
| US6846957B2 (en) | 2002-11-22 | 2005-01-25 | Board Of Regents, The University Of Texas System | Synthesis of 3-aminomethyl-1-propanol, a fluoxetine precursor |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4018895A (en) * | 1974-01-10 | 1977-04-19 | Eli Lilly And Company | Aryloxyphenylpropylamines in treating depression |
| IL99316A (en) * | 1991-08-27 | 1995-03-15 | Teva Pharma | Production of fluoxetine and new intermediates |
| US5618968A (en) * | 1993-02-05 | 1997-04-08 | Pliva Farmaceutska Kemijska, Prehrambena I Kozmeticka Industrija, Dionicko Drustvo | N-substituted derivatives of N-methyl-3-(p-trifluoromethylphenoxy)-3-phenylpropylamine and the procedure for their preparation |
-
1996
- 1996-09-10 HU HU9602469A patent/HU226690B1/hu unknown
-
1997
- 1997-09-10 SK SK290-99A patent/SK29099A3/sk unknown
- 1997-09-10 PL PL97332141A patent/PL332141A1/xx unknown
- 1997-09-10 WO PCT/HU1997/000050 patent/WO1998011054A1/en not_active Application Discontinuation
- 1997-09-10 EP EP97943082A patent/EP0929514A1/en not_active Withdrawn
- 1997-09-10 AU AU44689/97A patent/AU4468997A/en not_active Abandoned
- 1997-09-10 CZ CZ99752A patent/CZ75299A3/cs unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PL332141A1 (en) | 1999-08-30 |
| HUP9602469A3 (en) | 1999-06-28 |
| CZ75299A3 (cs) | 1999-09-15 |
| HU9602469D0 (en) | 1996-10-28 |
| WO1998011054A1 (en) | 1998-03-19 |
| HU226690B1 (en) | 2009-06-29 |
| AU4468997A (en) | 1998-04-02 |
| EP0929514A1 (en) | 1999-07-21 |
| HUP9602469A2 (hu) | 1998-09-28 |
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