HRP20010608A2 - Process for the production of paroxetine - Google Patents

Process for the production of paroxetine Download PDF

Info

Publication number: HRP20010608A2
Authority: HR; Croatia
Prior art keywords: compound; binap; formula; image; transition metal
Prior art date: 1999-02-23

Application number

HR20010608A

Other languages

English (en)

Croatian (hr)

Inventor

Renzo Rossi

Stefano Turchetta

Maria Donnarumma

Original Assignee

Recordati Chem Pharm

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1999-02-23

Filing date

2001-08-17

Publication date

2002-08-31

2001-08-17 Application filed by Recordati Chem Pharm filed Critical Recordati Chem Pharm

2002-08-31 Publication of HRP20010608A2 publication Critical patent/HRP20010608A2/hr

Links

238000000034 method Methods 0.000 title claims abstract description 43
AHOUBRCZNHFOSL-UHFFFAOYSA-N Paroxetine hydrochloride Natural products C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 title claims abstract description 26
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 title claims abstract description 21
229960002296 paroxetine Drugs 0.000 title claims abstract description 20
238000004519 manufacturing process Methods 0.000 title abstract 2
238000006243 chemical reaction Methods 0.000 claims abstract description 25
230000015572 biosynthetic process Effects 0.000 claims abstract description 22
239000003446 ligand Substances 0.000 claims abstract description 17
LUSZGTFNYDARNI-UHFFFAOYSA-N Sesamol Natural products OC1=CC=C2OCOC2=C1 LUSZGTFNYDARNI-UHFFFAOYSA-N 0.000 claims abstract description 14
238000005984 hydrogenation reaction Methods 0.000 claims abstract description 14
229910052723 transition metal Inorganic materials 0.000 claims abstract description 13
150000003624 transition metals Chemical class 0.000 claims abstract description 13
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 claims abstract description 8
238000006900 dealkylation reaction Methods 0.000 claims abstract description 3
238000010534 nucleophilic substitution reaction Methods 0.000 claims abstract description 3
150000001875 compounds Chemical class 0.000 claims description 42
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 35
MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 claims description 29
239000000203 mixture Substances 0.000 claims description 27
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 24
VURFVHCLMJOLKN-UHFFFAOYSA-N diphosphane Chemical compound PP VURFVHCLMJOLKN-UHFFFAOYSA-N 0.000 claims description 22
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 19
238000003786 synthesis reaction Methods 0.000 claims description 18
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 17
HFPZCAJZSCWRBC-UHFFFAOYSA-N p-cymene Chemical compound CC(C)C1=CC=C(C)C=C1 HFPZCAJZSCWRBC-UHFFFAOYSA-N 0.000 claims description 16
239000002904 solvent Substances 0.000 claims description 12
239000003153 chemical reaction reagent Substances 0.000 claims description 7
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 claims description 6
230000001476 alcoholic effect Effects 0.000 claims description 6
125000000217 alkyl group Chemical group 0.000 claims description 6
ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 claims description 6
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 6
239000012359 Methanesulfonyl chloride Substances 0.000 claims description 4
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 claims description 4
CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 claims description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 claims description 3
239000012442 inert solvent Substances 0.000 claims description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 2
125000004181 carboxyalkyl group Chemical group 0.000 claims description 2
238000005947 deacylation reaction Methods 0.000 claims description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
125000005843 halogen group Chemical group 0.000 claims description 2
229910052741 iridium Inorganic materials 0.000 claims description 2
GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 claims description 2
229910052703 rhodium Inorganic materials 0.000 claims description 2
239000010948 rhodium Substances 0.000 claims description 2
MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims description 2
229910052707 ruthenium Inorganic materials 0.000 claims description 2
150000007514 bases Chemical class 0.000 claims 2
230000036571 hydration Effects 0.000 claims 2
238000006703 hydration reaction Methods 0.000 claims 2
239000012327 Ruthenium complex Substances 0.000 claims 1
AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 claims 1
125000003944 tolyl group Chemical group 0.000 claims 1
239000000543 intermediate Substances 0.000 abstract description 4
230000000707 stereoselective effect Effects 0.000 abstract description 4
ZSYVGBLSRONTAI-UHFFFAOYSA-N [4-(4-fluorophenyl)-1,2,3,6-tetrahydropyridin-3-yl]methanol Chemical class OCC1CNCC=C1C1=CC=C(F)C=C1 ZSYVGBLSRONTAI-UHFFFAOYSA-N 0.000 abstract 1
238000001212 derivatisation Methods 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
239000000047 product Substances 0.000 description 23
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
239000000243 solution Substances 0.000 description 14
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 10
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
238000004128 high performance liquid chromatography Methods 0.000 description 10
239000003480 eluent Substances 0.000 description 9
239000012074 organic phase Substances 0.000 description 9
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
125000003118 aryl group Chemical group 0.000 description 8
125000003386 piperidinyl group Chemical group 0.000 description 8
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 7
238000005160 1H NMR spectroscopy Methods 0.000 description 6
229920000858 Cyclodextrin Polymers 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
VSWICNJIUPRZIK-UHFFFAOYSA-N 2-piperideine Chemical compound C1CNC=CC1 VSWICNJIUPRZIK-UHFFFAOYSA-N 0.000 description 5
239000001116 FEMA 4028 Substances 0.000 description 5
WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 5
235000011175 beta-cyclodextrine Nutrition 0.000 description 5
229960004853 betadex Drugs 0.000 description 5
BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 5
229910000397 disodium phosphate Inorganic materials 0.000 description 5
235000019800 disodium phosphate Nutrition 0.000 description 5
238000001914 filtration Methods 0.000 description 5
235000019799 monosodium phosphate Nutrition 0.000 description 5
AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 5
229910000162 sodium phosphate Inorganic materials 0.000 description 5
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
239000008346 aqueous phase Substances 0.000 description 4
238000002425 crystallisation Methods 0.000 description 4
230000008025 crystallization Effects 0.000 description 4
235000019256 formaldehyde Nutrition 0.000 description 4
HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 4
238000000926 separation method Methods 0.000 description 4
238000012360 testing method Methods 0.000 description 4
239000007836 KH2PO4 Substances 0.000 description 3
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
ZVQOOHYFBIDMTQ-UHFFFAOYSA-N [methyl(oxido){1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-lambda(6)-sulfanylidene]cyanamide Chemical compound N#CN=S(C)(=O)C(C)C1=CC=C(C(F)(F)F)N=C1 ZVQOOHYFBIDMTQ-UHFFFAOYSA-N 0.000 description 3
238000004458 analytical method Methods 0.000 description 3
239000003054 catalyst Substances 0.000 description 3
239000012043 crude product Substances 0.000 description 3
DHCWLIOIJZJFJE-UHFFFAOYSA-L dichlororuthenium Chemical compound Cl[Ru]Cl DHCWLIOIJZJFJE-UHFFFAOYSA-L 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
230000008020 evaporation Effects 0.000 description 3
239000012458 free base Substances 0.000 description 3
238000002844 melting Methods 0.000 description 3
230000008018 melting Effects 0.000 description 3
229910000402 monopotassium phosphate Inorganic materials 0.000 description 3
235000019796 monopotassium phosphate Nutrition 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
229960005183 paroxetine hydrochloride Drugs 0.000 description 3
GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 3
235000011149 sulphuric acid Nutrition 0.000 description 3
WVYWICLMDOOCFB-UHFFFAOYSA-N 4-methyl-2-pentanol Chemical compound CC(C)CC(C)O WVYWICLMDOOCFB-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
101100378191 Caenorhabditis elegans aco-2 gene Proteins 0.000 description 2
102000004190 Enzymes Human genes 0.000 description 2
108090000790 Enzymes Proteins 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
239000002585 base Substances 0.000 description 2
GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 2
238000006073 displacement reaction Methods 0.000 description 2
239000007789 gas Substances 0.000 description 2
238000002955 isolation Methods 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
239000012071 phase Substances 0.000 description 2
235000011007 phosphoric acid Nutrition 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
150000003839 salts Chemical class 0.000 description 2
239000007787 solid Substances 0.000 description 2
239000000725 suspension Substances 0.000 description 2
238000011282 treatment Methods 0.000 description 2
LAXRNWSASWOFOT-UHFFFAOYSA-J (cymene)ruthenium dichloride dimer Chemical compound [Cl-].[Cl-].[Cl-].[Cl-].[Ru+2].[Ru+2].CC(C)C1=CC=C(C)C=C1.CC(C)C1=CC=C(C)C=C1 LAXRNWSASWOFOT-UHFFFAOYSA-J 0.000 description 1
UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 description 1
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
VUQMOERHEHTWPE-UHFFFAOYSA-N 1-ethylpiperidin-2-one Chemical compound CCN1CCCCC1=O VUQMOERHEHTWPE-UHFFFAOYSA-N 0.000 description 1
LOAVXQCKIPZBNC-UHFFFAOYSA-N 5-ethenyl-2-fluoro-5-methylcyclohexa-1,3-diene Chemical compound C=CC1(C)CC=C(F)C=C1 LOAVXQCKIPZBNC-UHFFFAOYSA-N 0.000 description 1
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
235000011002 L(+)-tartaric acid Nutrition 0.000 description 1
239000001358 L(+)-tartaric acid Substances 0.000 description 1
FEWJPZIEWOKRBE-LWMBPPNESA-N L-(+)-Tartaric acid Natural products OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
238000003820 Medium-pressure liquid chromatography Methods 0.000 description 1
238000005481 NMR spectroscopy Methods 0.000 description 1
238000010478 Prins reaction Methods 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
WNHLGYRPKARUHY-UHFFFAOYSA-L [1-(2-diphenylphosphanylnaphthalen-1-yl)naphthalen-2-yl]-diphenylphosphane;1-methyl-4-propan-2-ylbenzene;ruthenium(2+);dichloride Chemical compound [Cl-].[Ru+]Cl.CC(C)C1=CC=C(C)C=C1.C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 WNHLGYRPKARUHY-UHFFFAOYSA-L 0.000 description 1
YCDRWGYVEXVMQX-UHFFFAOYSA-N [1-ethyl-4-(4-fluorophenyl)-3,6-dihydro-2h-pyridin-3-yl]methanol Chemical compound OCC1CN(CC)CC=C1C1=CC=C(F)C=C1 YCDRWGYVEXVMQX-UHFFFAOYSA-N 0.000 description 1
WHLQQRGHOPIIMQ-UHFFFAOYSA-N [2-(2-diphenylphosphanyl-6-methylphenyl)-3-methylphenyl]-diphenylphosphane Chemical compound CC=1C=CC=C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)C=1C=1C(C)=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 WHLQQRGHOPIIMQ-UHFFFAOYSA-N 0.000 description 1
230000009102 absorption Effects 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
230000002152 alkylating effect Effects 0.000 description 1
235000019270 ammonium chloride Nutrition 0.000 description 1
239000012736 aqueous medium Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
238000003556 assay Methods 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
CVXBEEMKQHEXEN-UHFFFAOYSA-N carbaryl Chemical class C1=CC=C2C(OC(=O)NC)=CC=CC2=C1 CVXBEEMKQHEXEN-UHFFFAOYSA-N 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
229950005499 carbon tetrachloride Drugs 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
238000006555 catalytic reaction Methods 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
XWBDWHCCBGMXKG-UHFFFAOYSA-N ethanamine;hydron;chloride Chemical compound Cl.CCN XWBDWHCCBGMXKG-UHFFFAOYSA-N 0.000 description 1
239000000284 extract Substances 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
125000001207 fluorophenyl group Chemical group 0.000 description 1
239000008241 heterogeneous mixture Substances 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
238000003384 imaging method Methods 0.000 description 1
239000007791 liquid phase Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
BRKADVNLTRCLOW-UHFFFAOYSA-M magnesium;fluorobenzene;bromide Chemical compound [Mg+2].[Br-].FC1=CC=[C-]C=C1 BRKADVNLTRCLOW-UHFFFAOYSA-M 0.000 description 1
238000003760 magnetic stirring Methods 0.000 description 1
239000011159 matrix material Substances 0.000 description 1
239000002609 medium Substances 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
238000002156 mixing Methods 0.000 description 1
PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical compound FC1=CC=CC=C1 PYLWMHQQBFSUBP-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
230000007935 neutral effect Effects 0.000 description 1
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000002243 precursor Substances 0.000 description 1
SSOLNOMRVKKSON-UHFFFAOYSA-N proguanil Chemical compound CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1 SSOLNOMRVKKSON-UHFFFAOYSA-N 0.000 description 1
238000000746 purification Methods 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
238000011084 recovery Methods 0.000 description 1
238000010992 reflux Methods 0.000 description 1
238000013341 scale-up Methods 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
238000004611 spectroscopical analysis Methods 0.000 description 1
238000003756 stirring Methods 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
239000000758 substrate Substances 0.000 description 1
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants

HR20010608A 1999-02-23 2001-08-17 Process for the production of paroxetine HRP20010608A2 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
IT1999MI000364A IT1308629B1 (it)	1999-02-23	1999-02-23	Processo per la produzione di paroxetina.
PCT/EP2000/001430 WO2000050422A1 (en)	1999-02-23	2000-02-22	Process for the production of paroxetine

Publications (1)

Publication Number	Publication Date
HRP20010608A2 true HRP20010608A2 (en)	2002-08-31

Family

ID=11382007

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
HR20010608A HRP20010608A2 (en)	1999-02-23	2001-08-17	Process for the production of paroxetine

Country Status (28)

Country	Link
US (1)	US6583287B1 (de)
EP (1)	EP1153023B1 (de)
JP (1)	JP2002537394A (de)
KR (1)	KR20010102366A (de)
CN (1)	CN1161353C (de)
AT (1)	ATE238295T1 (de)
AU (1)	AU759441B2 (de)
BR (1)	BR0008220A (de)
CA (1)	CA2361758A1 (de)
CZ (1)	CZ20012997A3 (de)
DE (1)	DE60002303T2 (de)
DK (1)	DK1153023T3 (de)
ES (1)	ES2195876T3 (de)
HK (1)	HK1040516B (de)
HR (1)	HRP20010608A2 (de)
HU (1)	HUP0105482A3 (de)
IL (1)	IL144883A (de)
IT (1)	IT1308629B1 (de)
MX (1)	MXPA01008502A (de)
NO (1)	NO319724B1 (de)
PL (1)	PL349358A1 (de)
PT (1)	PT1153023E (de)
RU (1)	RU2242473C2 (de)
SK (1)	SK12042001A3 (de)
TR (1)	TR200102441T2 (de)
TW (1)	TWI221473B (de)
WO (1)	WO2000050422A1 (de)
YU (1)	YU60801A (de)

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Publication number	Priority date	Publication date	Assignee	Title
ES2289650T3 (es) *	2004-03-03	2008-02-01	Chemi S.P.A.	Sal monosodica del acido 3-piridil-1-hidroxietiliden-1,1-bifosfonico amorfa y procedimiento para la preparacion de la misma.
US9138430B2 (en) *	2007-12-27	2015-09-22	Mylan Specialty L.P.	Formulation and method for the release of paroxetine in the large intestine
AU2013216123B2 (en) *	2012-01-31	2016-10-20	Eisai R&D Management Co., Ltd.	Paroxetine derivative
CN106831736A (zh) *	2017-02-15	2017-06-13	浙江华海药业股份有限公司	一种制备帕罗西汀杂质的方法
CN112521377A (zh) *	2020-11-26	2021-03-19	北京福元医药股份有限公司	一种盐酸帕罗西汀的连续化制备方法
CN115260153B (zh) *	2022-07-21	2023-10-27	威尚（上海）生物医药有限公司	一种6取代手性纯二氟哌啶喹唑啉衍生物及其制备方法

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JPH0757758B2 (ja)	1988-10-24	1995-06-21	高砂香料工業株式会社	ルテニウム―ホスフィン錯体
DK715988D0 (da) *	1988-12-22	1988-12-22	Ferrosan As	Etherifikation og dealkylering af piperidin-derivater samt intermediater
US5233084A (en) *	1989-06-22	1993-08-03	Monsanto Company	Method for preparing α-arylpropionic acids
FR2651152B1 (fr) *	1989-08-23	1991-11-29	Elf Aquitaine	Perfectionnement a la preparation de catalyseurs chiraux a base de complexes du ruthenium et du phosphore.
GB9209687D0 (en) *	1992-05-06	1992-06-17	Smithkline Beecham Plc	Novel process
DE4422672A1 (de) *	1994-06-30	1996-01-04	Hoechst Ag	Halogenierte Biphenyl-2,2'-diyl-bis-diphenylphosphine, ihre Herstellung und ihre Verwendung
HUP9900318A3 (en) *	1995-05-17	2001-09-28	Novo Nordisk As	Process for preparing 4-aryl-piperidine derivatives
HU221921B1 (hu) *	1996-07-08	2003-02-28	Richter Gedeon Vegyészeti Gyár Rt.	N-benzil-piperidin- és tetrahidropiridinszármazékok és eljárás azok előállítására
EP0983239A1 (de) *	1997-05-06	2000-03-08	Novo Nordisk A/S	Neue heterocyclische verbindungen
EP0920354B1 (de) *	1997-05-20	2003-12-03	Firmenich Sa	Ruthenium-katalysatoren und ihre verwendung zur asymmetrischen hydrierung von substraten mit schwacher koordination

1999
- 1999-02-23 IT IT1999MI000364A patent/IT1308629B1/it active
2000
- 2000-02-18 TW TW089102997A patent/TWI221473B/zh not_active IP Right Cessation
- 2000-02-22 AU AU31583/00A patent/AU759441B2/en not_active Ceased
- 2000-02-22 CA CA002361758A patent/CA2361758A1/en not_active Abandoned
- 2000-02-22 WO PCT/EP2000/001430 patent/WO2000050422A1/en not_active Application Discontinuation
- 2000-02-22 BR BR0008220-1A patent/BR0008220A/pt not_active IP Right Cessation
- 2000-02-22 KR KR1020017010760A patent/KR20010102366A/ko not_active Application Discontinuation
- 2000-02-22 EP EP00909228A patent/EP1153023B1/de not_active Expired - Lifetime
- 2000-02-22 PT PT00909228T patent/PT1153023E/pt unknown
- 2000-02-22 MX MXPA01008502A patent/MXPA01008502A/es active IP Right Grant
- 2000-02-22 SK SK1204-2001A patent/SK12042001A3/sk unknown
- 2000-02-22 US US09/890,414 patent/US6583287B1/en not_active Expired - Fee Related
- 2000-02-22 CN CNB008041873A patent/CN1161353C/zh not_active Expired - Fee Related
- 2000-02-22 DK DK00909228T patent/DK1153023T3/da active
- 2000-02-22 PL PL00349358A patent/PL349358A1/xx not_active IP Right Cessation
- 2000-02-22 TR TR2001/02441T patent/TR200102441T2/xx unknown
- 2000-02-22 IL IL14488300A patent/IL144883A/en not_active IP Right Cessation
- 2000-02-22 CZ CZ20012997A patent/CZ20012997A3/cs unknown
- 2000-02-22 AT AT00909228T patent/ATE238295T1/de not_active IP Right Cessation
- 2000-02-22 YU YU60801A patent/YU60801A/sh unknown
- 2000-02-22 HU HU0105482A patent/HUP0105482A3/hu unknown
- 2000-02-22 RU RU2001125933/04A patent/RU2242473C2/ru not_active IP Right Cessation
- 2000-02-22 DE DE60002303T patent/DE60002303T2/de not_active Expired - Fee Related
- 2000-02-22 ES ES00909228T patent/ES2195876T3/es not_active Expired - Lifetime
- 2000-02-22 JP JP2000601002A patent/JP2002537394A/ja active Pending
2001
- 2001-08-17 HR HR20010608A patent/HRP20010608A2/hr not_active Application Discontinuation
- 2001-08-22 NO NO20014078A patent/NO319724B1/no unknown
2002
- 2002-03-14 HK HK02101971.9A patent/HK1040516B/zh not_active IP Right Cessation

Also Published As

Publication number	Publication date
SK12042001A3 (sk)	2001-12-03
DE60002303D1 (de)	2003-05-28
WO2000050422A1 (en)	2000-08-31
YU60801A (sh)	2005-07-19
BR0008220A (pt)	2001-11-06
IL144883A (en)	2004-12-15
EP1153023A1 (de)	2001-11-14
HK1040516A1 (en)	2002-06-14
US6583287B1 (en)	2003-06-24
DE60002303T2 (de)	2004-04-01
NO20014078L (no)	2001-10-18
MXPA01008502A (es)	2003-06-06
ATE238295T1 (de)	2003-05-15
CN1161353C (zh)	2004-08-11
TR200102441T2 (tr)	2002-01-21
JP2002537394A (ja)	2002-11-05
IL144883A0 (en)	2002-06-30
PT1153023E (pt)	2003-09-30
NO20014078D0 (no)	2001-08-22
AU3158300A (en)	2000-09-14
NO319724B1 (no)	2005-09-05
TWI221473B (en)	2004-10-01
AU759441B2 (en)	2003-04-17
KR20010102366A (ko)	2001-11-15
EP1153023B1 (de)	2003-04-23
HUP0105482A3 (en)	2002-11-28
IT1308629B1 (it)	2002-01-09
ITMI990364A1 (it)	2000-08-23
HUP0105482A2 (en)	2002-08-28
CN1341113A (zh)	2002-03-20
PL349358A1 (en)	2002-07-15
CA2361758A1 (en)	2000-08-31
DK1153023T3 (da)	2003-08-11
CZ20012997A3 (cs)	2001-11-14
RU2242473C2 (ru)	2004-12-20
ES2195876T3 (es)	2003-12-16
HK1040516B (zh)	2003-10-31

Legal Events

Date	Code	Title
2002-08-31	A1OB	Publication of a patent application
2003-02-25	ARAI	Request for the grant of a patent on the basis of the submitted results of a substantive examination of a patent application
2008-12-08	OBST	Application withdrawn

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