[go: up one dir, main page]

WO2004005254A1 - Methode de production d'un compose de piperidine - Google Patents

Methode de production d'un compose de piperidine Download PDF

Info

Publication number
WO2004005254A1
WO2004005254A1 PCT/KR2003/001327 KR0301327W WO2004005254A1 WO 2004005254 A1 WO2004005254 A1 WO 2004005254A1 KR 0301327 W KR0301327 W KR 0301327W WO 2004005254 A1 WO2004005254 A1 WO 2004005254A1
Authority
WO
WIPO (PCT)
Prior art keywords
formula
compound
substituent
iii
producing
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/KR2003/001327
Other languages
English (en)
Inventor
Kwang-Min Lim
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
CLS LABORATORIES Inc
Original Assignee
CLS LABORATORIES Inc
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.)
Filing date
Publication date
Application filed by CLS LABORATORIES Inc filed Critical CLS LABORATORIES Inc
Priority to AU2003245102A priority Critical patent/AU2003245102A1/en
Publication of WO2004005254A1 publication Critical patent/WO2004005254A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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

Definitions

  • the present invention relates to a new process for producing a pharmaceutical intermediate compound for the preparation of paroxetine, more specifically 4- pheylpiperidine.
  • Paroxetine is well known as an anti-depressant, which is useful as a selective serotonin reuptake inhibitor, and has the following chemical formula:
  • U S. Patent No. 4,007,196 discloses a manufacturing method for paroxetine, in which an intermediate of formula (A) reacts with a sesamol compound of formula (C) to obtain the paroxetine as shown in the following reaction scheme.
  • an intermediate compound of formula (A) with a protected amine which is previously prepared through several manufacturing steps, is reacted with a sesamol of formula (C) so that paroxetine of formula (D) with a protected amine is produced
  • the amine is easily deprotected so as to obtain the paroxetine
  • U S Patent No 4, 902, 801 discloses a method for producing the intermediate compound of formula (A), which is suggested by Glaxo Smith Kline producing paroxetine on a commercial scale
  • the object of the present invention is to provide a method for producing a key intermediate compound which is very useful for producing paroxetine with a high product yield in a simple and moderate way without carrying out any complicated or dangerous processes
  • the present invention relates to a process for producing a pharmaceutical intermediate, 4-pheylpiperidine compound of formula (I)
  • the process comprises the steps of:
  • Y is a leaving group, preferably halogen including chlorine, bromine and iodine, methanesulfonyloxy or p-toluenesulfonyloxy;
  • Rl represents hydrogen, straight or branched C MO alkyl with or without substituent(s), straight or branched C MO alkoxy with or without substituent(s), aryl with or without substituent(s), formyl or alkylcarbonyl;
  • R2 represents alkoxycarbonyl, arylalkoxycarbonyl, aryloxycarbonyl or cyano.
  • Step 1 Preparation of the compound of formula (III).
  • the compound of formula (III) is obtained through cyclization and isomerization of the compound of formula (II) with base(s).
  • Y is a leaving group, preferably halogen including chlorine, bromine and iodine, methanesulfonyloxy or p-toluenesulfonyloxy
  • Rl represents hydrogen, straight or branched C M O alkyl with or without substituent(s), straight or branched C MO alkoxy with or without substituent(s), aryl with or without substituent(s), formyl or alkylcarbonyl
  • R2 represents alkoxycarbonyl, arylalkoxycarbonyl, aryloxycarbonyl or cyano
  • the bases used in the cyclization and isomerization may be either identical or different, and may be selected from the group consisting of alkali metal or its cyanide, carbonate, hydroxide, hydride, alkoxide, amide with or without substituent(s) and alkyl compound, alkaline earth metal or its cyanide, carbonate, hydroxide, hydride, alkoxide, amide with or without substituent(s) and alkyl compound, and the mixture thereof
  • the amount of the base is preferably 1 01 - 10 0 eq compared to the amount of the compound of formula (II)
  • the solvents used in the cyclization and isomerization may be either identical or different, and may be selected from the group consisting of an ether such as tetrahydrofuran, dioxane, petroleum ether, diethylether, dibutylether, t- butylmethylether and t-butylethylether, a polar organic solvent such as dialkoxyalkane, dimethylformamide, dimethylacetamide and dimethylsulfonamide, an amine such as ammonia, alkylamine, dialkylamine and trialkylamine, an aromatic hydrocarbon such as benzene, toluene and xylene, and an alcohol such as methanol, ethanol, isopropanol and t-butanol
  • an ether such as tetrahydrofuran, dioxane, petroleum ether, diethylether, dibutylether, t- butylmethylether and t-butylethylether
  • the reaction temperature is 150 °C or below, preferably -80 ° C ⁇ 100 ° C If the temperature is lower than -80 ° C , the reaction rate becomes slow If the temperature is above 150 ° C, side reactions may occur
  • the compound of formula (III) may be obtained in a quantitative amount with a product yield of 98% or higher without causing possible side reactions such as substitution reaction by the base and elimination reaction of HY
  • the compound of formula (I) is obtained from the compound of formula (III) by a reduction reaction using a reducing agent
  • Rl represents hydrogen, straight or branched C MO alkyl with or without substituent(s), straight or branched C MO alkoxy with or without substituent(s), aryl with or without substituent(s), formyl or alkylcarbonyl
  • R2 represents alkoxycarbonyl, arylalkoxycarbonyl, aryloxycarbonyl or cyano.
  • the reducing agent may be selected from the group consisting of borane; alkylborane; alane; alkylalane; borohydride, alkylborohydride, alkoxyborohydride or cyanoborohydride of alkali metal; borohydride, alkylborohydride, alkoxyborohydride or cyanoborohydride of alkaline earth metal; aluminumhydride, alkylaluminumhydride, or cyanoaluminumhydnde of alkali metal; aluminumhydride, alkylaluminumhydride, or cyanoaluminumhydride of alkaline earth metal; and hydrogen.
  • the reducing agent may be used preferably in an amount of 0.25 —2.0 eq. compared to the compound of formula (III).
  • a reaction solvent for the reduction reaction may be selected from the group consisting of an ether such as tetrahydrofuran, dioxane, petroleum ether, diethylether, dibutylether, t-butylmethylether and t-butylethylether; a polar organic solvent such as dialkoxyalkane, dimethylformamide, dimethylacetamide, and dimethylsulfonamide; an amine such as ammonia, alkylamine, dialkylamine, and trialkylamine; an aromatic hydrocarbon such as benzene, toluene and xylene; and an alcohol such as methanol, ethanol, isopropanol, and t-butanol.
  • an ether such as tetrahydrofuran, dioxane, petroleum ether, diethylether, dibutylether, t-butylmethylether and t-butylethylether
  • a polar organic solvent such as dialkoxyalkan
  • the reaction temperature is 100 ° C or below, preferably -30 °C ⁇ 80°C . If the temperature is lower than -30 ° C , the reaction rate becomes slow. If the temperature is above 100 ° C , side reactions may occur.
  • the chiral compound of formula (I) may be used as an intermediate compound for producing paroxetine, an anti-depressant, by the following reaction scheme as described above (refer to U.S. Patent No. 4,007,196).
  • the present invention provides a process for producing an intermediate compound for the preparation of paroxetine, an anti-depressant, in which the intermediate compound can be simply prepared in two stages with a high product yield and high purity of 99% or more, without going through any dangerous processes.
  • a highly pure paroxetine can be prepared in an economical and safe way.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Hydrogenated Pyridines (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

La présente invention concerne une nouvelle méthode de préparation d'un composé pharmaceutique intermédiaire de formule (I), dans laquelle R1 est hydrogène, alkyle C1-10 à chaîne droite ou ramifiée avec ou sans substituant(s), alcoxy C1-10 à chaîne droite ou ramifiée avec ou sans substituant(s), aryle avec ou sans substituant(s), formyle ou alkylcarbonyle. Grâce à la méthode de l'invention, ce composé intermédiaire de production de paroxetine peut être préparé de façon simple, pour un rendement élevé du produit et une haute pureté d'au moins 99 %, sans nécessité de mettre en oeuvre un quelconque procédé dangereux.
PCT/KR2003/001327 2002-07-05 2003-07-04 Methode de production d'un compose de piperidine Ceased WO2004005254A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2003245102A AU2003245102A1 (en) 2002-07-05 2003-07-04 Process for producing piperidine compound

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2002-0039088A KR100477048B1 (ko) 2002-07-05 2002-07-05 피페리딘 화합물의 새로운 제조방법
KR10-2002-0039088 2002-07-05

Publications (1)

Publication Number Publication Date
WO2004005254A1 true WO2004005254A1 (fr) 2004-01-15

Family

ID=30113084

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2003/001327 Ceased WO2004005254A1 (fr) 2002-07-05 2003-07-04 Methode de production d'un compose de piperidine

Country Status (3)

Country Link
KR (1) KR100477048B1 (fr)
AU (1) AU2003245102A1 (fr)
WO (1) WO2004005254A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005063707A1 (fr) * 2003-12-26 2005-07-14 Natco Pharma Limited Procede enantiospecifique permettant de preparer un intermediaire de paroxetine

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4007196A (en) * 1973-01-30 1977-02-08 A/S Ferrosan 4-Phenylpiperidine compounds
US4902801A (en) * 1985-08-10 1990-02-20 Beecham Group Plc. Process for preparing aryl-piperidine carbinols and novel intermediates used in the process
WO1997024323A1 (fr) * 1995-12-28 1997-07-10 Chirotech Technology Procede de preparation de piperidines a substitution 4-aryl-3-hydromethyle, optiquement enrichies destinees a etre utilisees comme intermediaires dans la synthese de la paroxetine
EP0812827A1 (fr) * 1996-06-13 1997-12-17 SUMIKA FINE CHEMICALS Co., Ltd. Dérivés de pipéridine comme intermédiaire pour la production de paroxétine et procédé pour leur préparation
WO2002068416A2 (fr) * 2001-02-24 2002-09-06 Spurcourt Limited Procede de preparation de la paroxetine et intermediaires a cet usage

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4007196A (en) * 1973-01-30 1977-02-08 A/S Ferrosan 4-Phenylpiperidine compounds
US4902801A (en) * 1985-08-10 1990-02-20 Beecham Group Plc. Process for preparing aryl-piperidine carbinols and novel intermediates used in the process
WO1997024323A1 (fr) * 1995-12-28 1997-07-10 Chirotech Technology Procede de preparation de piperidines a substitution 4-aryl-3-hydromethyle, optiquement enrichies destinees a etre utilisees comme intermediaires dans la synthese de la paroxetine
EP0812827A1 (fr) * 1996-06-13 1997-12-17 SUMIKA FINE CHEMICALS Co., Ltd. Dérivés de pipéridine comme intermédiaire pour la production de paroxétine et procédé pour leur préparation
WO2002068416A2 (fr) * 2001-02-24 2002-09-06 Spurcourt Limited Procede de preparation de la paroxetine et intermediaires a cet usage

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005063707A1 (fr) * 2003-12-26 2005-07-14 Natco Pharma Limited Procede enantiospecifique permettant de preparer un intermediaire de paroxetine

Also Published As

Publication number Publication date
KR100477048B1 (ko) 2005-03-17
AU2003245102A1 (en) 2004-01-23
KR20040004745A (ko) 2004-01-14

Similar Documents

Publication Publication Date Title
RU2514935C2 (ru) Способ получения стимулятора апоптоза авт-263
JP3740050B2 (ja) ケトンの還元用キラル触媒とその製法
JPH052678B2 (fr)
JPH05213838A (ja) フルオキセチンの製法
KR100286874B1 (ko) 보호된 4-아미노메틸-피롤리딘-3-온의 제조방법
US20040106818A1 (en) Process for the preparation of cyclohexanol derivatives
US3873597A (en) 2-Bromo-2-bromomethylglutaronitrile
JP3173602B2 (ja) エンイン誘導体の新規製造中間体及びその製造法
KR960000758B1 (ko) 광학적 활성 히드록시벤질아민 유도체 및 그의 제조방법
Branchaud Studies on the development of the tritylsulfenyl group as a nitrogen protecting group and application in a synthesis of. delta.-coniceine
WO2004005254A1 (fr) Methode de production d'un compose de piperidine
KR100741413B1 (ko) 3-치환된 벤조트리플루오라이드의 선택적 탈양자화 및작용화 방법
CN107652226B (zh) 一种N-Boc-4-哌啶甲醛的制备方法
US6515141B1 (en) Process for the preparation of indole derivatives or salts thereof
TWI423957B (zh) 吡啶硼烷複合物
CN112142664B (zh) 一种多取代萘并氮杂环类化合物的合成方法
JP4173599B2 (ja) ６−ヒドロキシ−２−オキソ−１，２，３，４−テトラヒドロキノリンの製造方法
JP3959178B2 (ja) ヒドラジン誘導体の製造方法、その中間体および中間体の製造方法
EP3904333A1 (fr) Procédé de préparation de (2s,3s)-3-amino-bicyclo[2.2.2]octane-2-carboxylate
CZ2002138A3 (cs) Způsob přípravy midodrinu a meziprodukt tohoto způsobu
JP2664438B2 (ja) Ｎ−（２−クロロベンジル）−２−（２−チエニル）エチルアミンの製法
JP2019196323A (ja) ９−（１−ナフチル）−９ｈ−カルバゾール誘導体の製造方法
KR100368896B1 (ko) 6-아미노메틸-5Ｈ-디벤즈[ｂ,ｅ]아제핀의 제조방법
JPS63135393A (ja) アルキルシリルシアニドの製造方法
JP2512958B2 (ja) １−ビフェニリルエタノ―ル誘導体およびその製法

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP

WWW Wipo information: withdrawn in national office

Country of ref document: JP