UA61952C2 - A chemical process for reduction of 1-substituted 3-hydroxymethyl-4-(4-fluorophenyl)tetrahydropyridines - Google Patents
A chemical process for reduction of 1-substituted 3-hydroxymethyl-4-(4-fluorophenyl)tetrahydropyridines Download PDFInfo
- Publication number
- UA61952C2 UA61952C2 UA99126877A UA99126877A UA61952C2 UA 61952 C2 UA61952 C2 UA 61952C2 UA 99126877 A UA99126877 A UA 99126877A UA 99126877 A UA99126877 A UA 99126877A UA 61952 C2 UA61952 C2 UA 61952C2
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- UA
- Ukraine
- Prior art keywords
- differs
- formula
- compound
- sodium
- lithium
- Prior art date
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- -1 1-substituted 3-hydroxymethyl-4-(4-fluorophenyl)tetrahydropyridines Chemical class 0.000 title claims description 33
- 230000009467 reduction Effects 0.000 title claims description 6
- 238000001311 chemical methods and process Methods 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 41
- 238000000034 method Methods 0.000 claims abstract description 28
- 229910017053 inorganic salt Inorganic materials 0.000 claims abstract description 18
- 229910052987 metal hydride Inorganic materials 0.000 claims abstract description 14
- 150000004681 metal hydrides Chemical class 0.000 claims abstract description 14
- 239000003085 diluting agent Substances 0.000 claims abstract description 12
- 230000008569 process Effects 0.000 claims abstract description 3
- 239000000203 mixture Substances 0.000 claims description 26
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims description 22
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 11
- 229910052744 lithium Inorganic materials 0.000 claims description 11
- 229910001629 magnesium chloride Inorganic materials 0.000 claims description 11
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 10
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 10
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 8
- 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 claims description 8
- 239000011777 magnesium Substances 0.000 claims description 8
- 229910052749 magnesium Inorganic materials 0.000 claims description 8
- 229910052708 sodium Inorganic materials 0.000 claims description 8
- 239000011734 sodium Substances 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 125000006239 protecting group Chemical group 0.000 claims description 6
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 5
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 229910052742 iron Inorganic materials 0.000 claims description 5
- 229910052746 lanthanum Inorganic materials 0.000 claims description 5
- FZLIPJUXYLNCLC-UHFFFAOYSA-N lanthanum atom Chemical compound [La] FZLIPJUXYLNCLC-UHFFFAOYSA-N 0.000 claims description 5
- 229910001623 magnesium bromide Inorganic materials 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 229910052725 zinc Inorganic materials 0.000 claims description 5
- 239000011701 zinc Substances 0.000 claims description 5
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 4
- LUSZGTFNYDARNI-UHFFFAOYSA-N Sesamol Chemical compound OC1=CC=C2OCOC2=C1 LUSZGTFNYDARNI-UHFFFAOYSA-N 0.000 claims description 4
- 239000011575 calcium Substances 0.000 claims description 4
- 229910052791 calcium Inorganic materials 0.000 claims description 4
- 229910001641 magnesium iodide Inorganic materials 0.000 claims description 4
- 229910052700 potassium Inorganic materials 0.000 claims description 4
- 239000011591 potassium Substances 0.000 claims description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 3
- 239000004215 Carbon black (E152) Substances 0.000 claims description 3
- 229930195733 hydrocarbon Natural products 0.000 claims description 3
- 150000002430 hydrocarbons Chemical class 0.000 claims description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
- CSDQQAQKBAQLLE-UHFFFAOYSA-N 4-(4-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine Chemical compound C1=CC(Cl)=CC=C1C1C(C=CS2)=C2CCN1 CSDQQAQKBAQLLE-UHFFFAOYSA-N 0.000 claims description 2
- CGKRFDXHYBJWPO-UHFFFAOYSA-N C(C)[AlH]CC.[Na] Chemical compound C(C)[AlH]CC.[Na] CGKRFDXHYBJWPO-UHFFFAOYSA-N 0.000 claims description 2
- 239000012448 Lithium borohydride Substances 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 150000003863 ammonium salts Chemical class 0.000 claims description 2
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 230000003993 interaction Effects 0.000 claims description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 2
- 125000005147 toluenesulfonyl group Chemical group C=1(C(=CC=CC1)S(=O)(=O)*)C 0.000 claims description 2
- 125000004950 trifluoroalkyl group Chemical group 0.000 claims description 2
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- DNEHKUCSURWDGO-UHFFFAOYSA-N aluminum sodium Chemical compound [Na].[Al] DNEHKUCSURWDGO-UHFFFAOYSA-N 0.000 claims 1
- 238000002955 isolation Methods 0.000 claims 1
- 238000012876 topography Methods 0.000 claims 1
- 230000009466 transformation Effects 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 5
- 125000006242 amine protecting group Chemical group 0.000 abstract 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 54
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 27
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 238000004128 high performance liquid chromatography Methods 0.000 description 14
- 238000001030 gas--liquid chromatography Methods 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 description 8
- AHOUBRCZNHFOSL-UHFFFAOYSA-N Paroxetine hydrochloride Natural products C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 239000012299 nitrogen atmosphere Substances 0.000 description 6
- 229960002296 paroxetine Drugs 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 238000010606 normalization Methods 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000006115 defluorination reaction Methods 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 125000003884 phenylalkyl group Chemical group 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 1
- UIOFUWFRIANQPC-JKIFEVAISA-N Floxacillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C1=C(C)ON=C1C1=C(F)C=CC=C1Cl UIOFUWFRIANQPC-JKIFEVAISA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- AELJBFRPEBTCSA-HKUYNNGSSA-N [(3s,4r)-1-benzyl-4-(4-fluorophenyl)piperidin-3-yl]methanol Chemical compound C([C@H]([C@@H](CC1)C=2C=CC(F)=CC=2)CO)N1CC1=CC=CC=C1 AELJBFRPEBTCSA-HKUYNNGSSA-N 0.000 description 1
- FBWOVKPOBYIMHY-OALUTQOASA-N [(3s,4r)-1-benzyl-4-phenylpiperidin-3-yl]methanol Chemical compound C([C@H]([C@@H](CC1)C=2C=CC=CC=2)CO)N1CC1=CC=CC=C1 FBWOVKPOBYIMHY-OALUTQOASA-N 0.000 description 1
- GANNOFFDYMSBSZ-UHFFFAOYSA-N [AlH3].[Mg] Chemical compound [AlH3].[Mg] GANNOFFDYMSBSZ-UHFFFAOYSA-N 0.000 description 1
- VCHVXUQQZMQWIY-UHFFFAOYSA-N [AlH3].[Mg].[Li] Chemical compound [AlH3].[Mg].[Li] VCHVXUQQZMQWIY-UHFFFAOYSA-N 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 125000001033 ether group Chemical group 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- ORUIBWPALBXDOA-UHFFFAOYSA-L magnesium fluoride Chemical compound [F-].[F-].[Mg+2] ORUIBWPALBXDOA-UHFFFAOYSA-L 0.000 description 1
- 229910001635 magnesium fluoride Inorganic materials 0.000 description 1
- 229910012375 magnesium hydride Inorganic materials 0.000 description 1
- BLQJIBCZHWBKSL-UHFFFAOYSA-L magnesium iodide Chemical compound [Mg+2].[I-].[I-] BLQJIBCZHWBKSL-UHFFFAOYSA-L 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N methyl monoether Natural products COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- XQCHMGAOAWZUPI-UHFFFAOYSA-M sodium;butane-1-sulfonate Chemical compound [Na+].CCCCS([O-])(=O)=O XQCHMGAOAWZUPI-UHFFFAOYSA-M 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
- C07D211/22—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/34—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/70—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Hydrogenated Pyridines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9710004.4A GB9710004D0 (en) | 1997-05-17 | 1997-05-17 | Chemical process |
| PCT/EP1998/002826 WO1998052920A1 (en) | 1997-05-17 | 1998-05-13 | Chemical process for the reduction of 1-substituted -3-hydroxymethyl-4- (4-fluorophenyl)tetrahydropyridines |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UA61952C2 true UA61952C2 (en) | 2003-12-15 |
Family
ID=10812456
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| UA99126877A UA61952C2 (en) | 1997-05-17 | 1998-05-13 | A chemical process for reduction of 1-substituted 3-hydroxymethyl-4-(4-fluorophenyl)tetrahydropyridines |
Country Status (28)
| Country | Link |
|---|---|
| US (1) | US6326496B1 (de) |
| EP (1) | EP0983237B1 (de) |
| JP (1) | JP4463883B2 (de) |
| KR (1) | KR100515852B1 (de) |
| CN (1) | CN1121386C (de) |
| AR (1) | AR012688A1 (de) |
| AT (1) | ATE212013T1 (de) |
| AU (1) | AU748902B2 (de) |
| BG (1) | BG63847B1 (de) |
| BR (1) | BR9809809B1 (de) |
| CA (1) | CA2289013C (de) |
| CZ (1) | CZ292282B6 (de) |
| DE (1) | DE69803178T2 (de) |
| DK (1) | DK0983237T3 (de) |
| ES (1) | ES2171299T3 (de) |
| GB (1) | GB9710004D0 (de) |
| HU (1) | HUP0002709A3 (de) |
| ID (1) | ID24181A (de) |
| IL (1) | IL132360A (de) |
| NO (1) | NO313326B1 (de) |
| NZ (1) | NZ501692A (de) |
| PL (1) | PL189464B1 (de) |
| PT (1) | PT983237E (de) |
| RU (1) | RU2205178C2 (de) |
| SK (1) | SK149599A3 (de) |
| TR (1) | TR199902823T2 (de) |
| UA (1) | UA61952C2 (de) |
| WO (1) | WO1998052920A1 (de) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2000246280A1 (en) * | 2000-05-12 | 2001-11-20 | Synthon B.V. | Tosylate salts of 4-(p-fluorophenyl)-piperidine-3-carbinols |
| GB0021147D0 (en) | 2000-08-30 | 2000-10-11 | Knoll Ag | Chemical process |
| US6777554B2 (en) | 2001-02-05 | 2004-08-17 | Teva Pharmaceutical Industries Ltd. | Preparation of N-methylparoxetine and related intermediate compounds |
| US6930186B2 (en) | 2001-06-13 | 2005-08-16 | Teva Pharmacetical Industries Ltd. | Process for the preparation of paroxetine substantially free of alkoxy impurities |
| US20050266082A1 (en) * | 2004-05-26 | 2005-12-01 | Patel Satishkumar A | Preparation of stable paroxetine HC1 ER tablets using a melt granulation process |
| US20070112031A1 (en) * | 2005-11-14 | 2007-05-17 | Gant Thomas G | Substituted phenylpiperidines with serotoninergic activity and enhanced therapeutic properties |
| US20080033050A1 (en) | 2006-08-04 | 2008-02-07 | Richards Patricia Allison Tewe | Method of treating thermoregulatory disfunction with paroxetine |
| US9138430B2 (en) * | 2007-12-27 | 2015-09-22 | Mylan Specialty L.P. | Formulation and method for the release of paroxetine in the large intestine |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3849542A (en) * | 1966-05-09 | 1974-11-19 | Dow Chemical Co | Lithium magnesium aluminum hydride |
| GB1422263A (en) | 1973-01-30 | 1976-01-21 | Ferrosan As | 4-phenyl-piperidine compounds |
| EP0223334B1 (de) * | 1985-08-10 | 1991-07-10 | Beecham Group Plc | Verfahren zur Herstellung von Arylpiperidincarbinol |
| EP0299549A3 (de) * | 1987-07-09 | 1989-02-08 | Duphar International Research B.V | Tertiäre 2,5-Dialkyl-3-phenyl-piperidin-Derivate mit Opiatantagonistischer Wirkung |
| GB9100505D0 (en) * | 1991-01-10 | 1991-02-20 | Shell Int Research | Piperidine derivatives |
| US5258517A (en) * | 1992-08-06 | 1993-11-02 | Sepracor, Inc. | Method of preparing optically pure precursors of paroxetine |
| GB9305175D0 (en) * | 1993-03-13 | 1993-04-28 | Smithkline Beecham Plc | Novel process |
| WO1996036636A1 (en) * | 1995-05-17 | 1996-11-21 | Novo Nordisk A/S | Process for preparing 4-aryl-piperidine derivatives |
| ES2331937T3 (es) * | 1996-06-13 | 2010-01-20 | Sumitomo Chemical Company, Limited | Derivados de piperidina como intermediarios para la preparacion de paroxetina y procedimiento de preparacion de los mismos. |
| HU221921B1 (hu) | 1996-07-08 | 2003-02-28 | Richter Gedeon Vegyészeti Gyár Rt. | N-benzil-piperidin- és tetrahidropiridinszármazékok és eljárás azok előállítására |
| GB9623359D0 (en) * | 1996-11-09 | 1997-01-08 | Smithkline Beecham Plc | Novel process |
-
1997
- 1997-05-17 GB GBGB9710004.4A patent/GB9710004D0/en active Pending
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1998
- 1998-05-12 AR ARP980102206A patent/AR012688A1/es unknown
- 1998-05-13 PT PT98929307T patent/PT983237E/pt unknown
- 1998-05-13 IL IL13236098A patent/IL132360A/xx not_active IP Right Cessation
- 1998-05-13 SK SK1495-99A patent/SK149599A3/sk unknown
- 1998-05-13 CA CA002289013A patent/CA2289013C/en not_active Expired - Fee Related
- 1998-05-13 ID IDW991271A patent/ID24181A/id unknown
- 1998-05-13 AT AT98929307T patent/ATE212013T1/de not_active IP Right Cessation
- 1998-05-13 EP EP98929307A patent/EP0983237B1/de not_active Expired - Lifetime
- 1998-05-13 KR KR10-1999-7010581A patent/KR100515852B1/ko not_active IP Right Cessation
- 1998-05-13 AU AU79121/98A patent/AU748902B2/en not_active Ceased
- 1998-05-13 DE DE69803178T patent/DE69803178T2/de not_active Expired - Lifetime
- 1998-05-13 ES ES98929307T patent/ES2171299T3/es not_active Expired - Lifetime
- 1998-05-13 CZ CZ19994081A patent/CZ292282B6/cs not_active IP Right Cessation
- 1998-05-13 UA UA99126877A patent/UA61952C2/uk unknown
- 1998-05-13 CN CN98805113A patent/CN1121386C/zh not_active Expired - Fee Related
- 1998-05-13 HU HU0002709A patent/HUP0002709A3/hu unknown
- 1998-05-13 NZ NZ501692A patent/NZ501692A/en unknown
- 1998-05-13 JP JP54990898A patent/JP4463883B2/ja not_active Expired - Fee Related
- 1998-05-13 DK DK98929307T patent/DK0983237T3/da active
- 1998-05-13 TR TR1999/02823T patent/TR199902823T2/xx unknown
- 1998-05-13 WO PCT/EP1998/002826 patent/WO1998052920A1/en active IP Right Grant
- 1998-05-13 RU RU99127285/04A patent/RU2205178C2/ru not_active IP Right Cessation
- 1998-05-13 PL PL98336796A patent/PL189464B1/pl not_active IP Right Cessation
- 1998-05-13 BR BRPI9809809-8A patent/BR9809809B1/pt not_active IP Right Cessation
- 1998-05-13 US US09/423,749 patent/US6326496B1/en not_active Expired - Fee Related
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1999
- 1999-10-26 BG BG103834A patent/BG63847B1/bg unknown
- 1999-11-16 NO NO19995619A patent/NO313326B1/no unknown
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