[go: up one dir, main page]

WO2005016906A1 - Procede de fabrication de rofecoxibe - Google Patents

Procede de fabrication de rofecoxibe Download PDF

Info

Publication number
WO2005016906A1
WO2005016906A1 PCT/IN2003/000271 IN0300271W WO2005016906A1 WO 2005016906 A1 WO2005016906 A1 WO 2005016906A1 IN 0300271 W IN0300271 W IN 0300271W WO 2005016906 A1 WO2005016906 A1 WO 2005016906A1
Authority
WO
WIPO (PCT)
Prior art keywords
phenyl
furanone
rofecoxib
solvent
methyl
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/IN2003/000271
Other languages
English (en)
Inventor
T. V. S. K Vittal
Krishna M. Hari
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.)
Shasun Chemicals and Drugs Ltd
Original Assignee
Shasun Chemicals and Drugs Ltd
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 Shasun Chemicals and Drugs Ltd filed Critical Shasun Chemicals and Drugs Ltd
Priority to AU2003263582A priority Critical patent/AU2003263582A1/en
Priority to PCT/IN2003/000271 priority patent/WO2005016906A1/fr
Publication of WO2005016906A1 publication Critical patent/WO2005016906A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D307/58—One oxygen atom, e.g. butenolide

Definitions

  • the present invention provides a simplified and commercial scale process for the manufacture of rofecoxib.
  • the invention comprises of oxidizing 4-(4-me ⁇ yltl ⁇ iophenyl)-3-phenyl-2(5E ⁇ -furanone using hydrogen peroxide as oxidant, acetic acid as solvent and sodium tungstate as catalyst under suitable reaction conditions to get rofecoxib.
  • Rofecoxib is described chemically as 4-[4-(methy]-sulfonyl)phenyl]-3- phenyl-2(5H)-furanone. It has the following chemical structure:
  • Rofecoxib is a nonsteroidal anti-inflammatory drug that exhibits anti- inflammatory, analgesic, and antipyretic activities.
  • the mechanism of action of Rofecoxib is believed to be due to inhibition of prostaglandin synthesis, via inhibition of cyclooxygenase-2 (COX-2).
  • COX-2 cyclooxygenase-2
  • the literature describes many methods of preparing 4-[4- (methylsulfonyl)phehyl]-3-phenyl-2(5H)-furanone, herein after referred to as 'rofecoxib', from a variety of starting materials.
  • 5,840,924 described another process for the preparation of rofecoxib starting from thioanisole, wherein the thioanisole is converted in to 2-bromo- l-(4-(methylsulfonyl)phenyl)ethanone in three steps, and then condensed with sodium phenylacetate to get the ester derivative.
  • This ester derivative is then cyclized in the presence of a organic base to get crude rofecoxib, which upon purification by re- crystallization gave pure rofecoxib.
  • 5,585,504 described a process for the preparation of rofecoxib by oxidation of 4-(4-methylthiophenyl)-3-phenyl-2(5H)-furanone using oxone.
  • This patent specification also described a process for the preparation of 4-(4-memylt-hiophenyl)-3-phenyl-2(5H)-furanone from 3- bromo-4-(4-(memylthio)-phenyl)-2(5H)-furanone or 3-triflurosulfonyl-4-(4- (methylthio)-phenyl)-2(5H)-furanone by condensation with 4-methylthio- phenylboric acid in the presence of Pd(PPh 3 ) 4 .
  • the present method comprises of oxidizing 4-(4-methylthiophenyl)-3-phenyl-2(5H)-furanone using hydrogen peroxide as oxidant, acetic acid as solvent and sodium tungstate as catalyst under suitable reaction conditions to get rofecoxib.
  • the present invention describes a simplified and commercial scale process for the manufacture of rofecoxib, wherein 4-(4-methylthiophenyl)- 3-phenyl-2(5H)-furanone is oxidized to get rofecoxib.
  • 4-(4-methyltmophenyl)-3-phenyl-2(5H)-furanone is dissolved in carboxylic acid and then oxidized in presence of sodium tungstate or sodium tungstate dihydrate as catalyst using hydrogen peroxide as oxidant.
  • the preferred carboxylic acid of the present invention is acetic acid.
  • the solvent acetic acid quantity used for the reaction could be between 5 to 15 times the volume of 4-(4-methylthiophenyl)-3-phenyl-2(5H)-furanone to be oxidized, and preferably between 7 to 8 times the volume.
  • the amount of catalyst sodium tungstate used for the oxidation could be between 1 to 5% by weight of the 3-phenyl-4-(methylthio)phenyl- 2-(5H)-furanone, and preferably 1 to 2% by weight.
  • the concentration of hydrogen peroxide used for the oxidation could be 10 to 50% weight / weight as aqueous solution and preferred concentration of hydrogen peroxide for the oxidation of 4-(4- methylthiophenyl)-3-phenyl-2(5H)-furanone is 25 to 35% weight / weight as aqueous solution.
  • the oxidation of 4-(4-methylthiophenyl)-3-phenyl- 2(5H)-furanone to rofecoxib by the present invention is carried out in presence of a large excess of hydrogen peroxide.
  • the hydrogen peroxide quantity used for this oxidation could be between 8 to 15 moles for oxidizing every mole of 4-(4-methylti ⁇ iophenyl)-3-phenyl-2(5H)-furanone to rofecoxib.
  • the preferred molar ratio of hydrogen peroxide is between 10 to 12 for every mole of 3-phenyl-4-(methylthio)phenyl-2-(5H)-furanone.
  • the oxidation of 4-(4-methyltJ ⁇ iophenyl)-3-phenyl-2(5H)-furanone to rofecoxib by the present invention could be carried out at a temperature between 70 to 100° and preferably between 75 to 85 °G As the oxidation is exothermic the reaction temperature is maintained by controlling the hydrogen peroxide addition rate. Hydrogen peroxide is added into the reaction mixture slowly over a period of 2 to 5 hr, and preferably over 2 to 3 hr. The reaction is continued till the desired level of conversion is achieved, and the progress of the reaction is monitored by TLC analysis for the absence of 4-(4-methylthiophenyl)-3-phenyl-2(5H)-furanone.
  • the reaction mixture is cooled to 20 to 35°C and preferably between 25 to 30°C
  • the product crystallized from the reaction mixture is then separated by filtration or centrifugation.
  • the filtered product is washed with water till the pH of the washings is 4.0 to 7.0 and preferably 6.0 to 7.0.
  • the product obtained by the process described in the present invention is then optionally purified by dissolving it in about 4 volumes of N,N-dimethylformamide at 80 to 85° diluting the solution by adding about 6 volumes of methanol at 60 to 65 °G
  • the solution is then cooled slowly to 30 to 35°C and filtered.
  • Example -1 Preparation of 4-[4-(methylsulfonyl)phenyl]-3-phenyl-2(5-f ⁇ )-furanone Dissolved 4-(4-methylthiophenyl)-3-phenyl-2(5F ⁇ )-furanone (100 g) in acetic acid (770 ml) and added in to the solution is sodium tungstate (1.2 g).
  • the solution is heated to 80°C and added in to the solution is hydrogen peroxide (30% wt/wt, 385 ml) slowly over a period of 2 hr.
  • the reaction is continued till 4-(4-methylthiophenyl)-3-phenyl-2(5H)-furanone is absent by TLC
  • the reaction mixture is then cooled slowly to 30°C and the product is filtered.
  • the product is washed with water several times till the pH of the filtrate is 6.
  • Example - 2 Purification of 4-[4-(methylsulfonyl)phenyl]-3-phenyl-2(5-f9-furanone Dissolved 4-[4- (methykulfonyl)phenyl]-3-phenyl-2(5iJ -furanone (rofecoxib, 100 g) in N,N-climethylformamide (400 ml) at 80°C Added in to the solution methanol (600 ml) at 60 to 65 °C The solution is then cooled to 30 to 35 °C over a period of 3hr. The product is filtered and then the wet product is recharged in to methanol (1000 ml) and the slurry boiled to reflux for 5 hrs.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Furan Compounds (AREA)

Abstract

L'invention concerne un procédé simplifié d'échelle commerciale destiné à fabriquer du rofecoxibe. L'invention consiste à oxyder du 4-(4-méthylthiophényl)-3-phényl-2(5H)-furanone au moyen de peroxyde d'hydrogène servant d'oxydant, d'acide acétique servant de solvant et de tungstate de sodium servant de catalyseur, dans des conditions réactionnelles appropriées, pour obtenir du rofecoxibe.
PCT/IN2003/000271 2003-08-14 2003-08-14 Procede de fabrication de rofecoxibe Ceased WO2005016906A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU2003263582A AU2003263582A1 (en) 2003-08-14 2003-08-14 Process for the manufacture of rofecoxib
PCT/IN2003/000271 WO2005016906A1 (fr) 2003-08-14 2003-08-14 Procede de fabrication de rofecoxibe

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/IN2003/000271 WO2005016906A1 (fr) 2003-08-14 2003-08-14 Procede de fabrication de rofecoxibe

Publications (1)

Publication Number Publication Date
WO2005016906A1 true WO2005016906A1 (fr) 2005-02-24

Family

ID=34179260

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2003/000271 Ceased WO2005016906A1 (fr) 2003-08-14 2003-08-14 Procede de fabrication de rofecoxibe

Country Status (2)

Country Link
AU (1) AU2003263582A1 (fr)
WO (1) WO2005016906A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020106522A1 (fr) * 2018-11-21 2020-05-28 Tremeau Pharmaceuticals, Inc. Formes purifiées de rofécoxib et procédés de fabrication et d'utilisation
US10945992B1 (en) 2019-11-13 2021-03-16 Tremeau Pharmaceuticals, Inc. Dosage forms of rofecoxib and related methods
US11858909B2 (en) 2021-04-09 2024-01-02 Tremeau Pharmaceuticals, Inc. Deuterated etoricoxib, methods of manufacture, and use thereof

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5585504A (en) * 1994-09-16 1996-12-17 Merck & Co., Inc. Process of making cox-2 inhibitors having a lactone bridge
WO2001029004A1 (fr) * 1999-10-15 2001-04-26 Zambon Group S.P.A. Processus d'oxydation pour la preparation d'intermediaires utiles dans la synthese de diarylpyridines

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5585504A (en) * 1994-09-16 1996-12-17 Merck & Co., Inc. Process of making cox-2 inhibitors having a lactone bridge
WO2001029004A1 (fr) * 1999-10-15 2001-04-26 Zambon Group S.P.A. Processus d'oxydation pour la preparation d'intermediaires utiles dans la synthese de diarylpyridines

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20220409568A1 (en) * 2018-11-21 2022-12-29 Tremeau Pharmaceuticals, Inc. Purified forms of rofecoxib, methods of manufacture and use
US10987337B2 (en) 2018-11-21 2021-04-27 Tremeau Pharmaceuticals, Inc. Purified forms of rofecoxib, methods of manufacture and use
CN113660934A (zh) * 2018-11-21 2021-11-16 特默罗制药股份有限公司 罗非昔布的纯化形式、制备方法和用途
JP2022508200A (ja) * 2018-11-21 2022-01-19 トレモ― ファーマシューティカルズ，インコーポレーテッド ロフェコキシブの精製形態、製造方法および使用
US20220378736A1 (en) * 2018-11-21 2022-12-01 Tremeau Pharmaceuticals, Inc. Purified forms of rofecoxib, methods of manufacture and use
WO2020106522A1 (fr) * 2018-11-21 2020-05-28 Tremeau Pharmaceuticals, Inc. Formes purifiées de rofécoxib et procédés de fabrication et d'utilisation
US11559509B2 (en) 2018-11-21 2023-01-24 Tremeau Pharmaceuticals, Inc. Purified forms of rofecoxib, methods of manufacture and use
US11576890B2 (en) 2018-11-21 2023-02-14 Tremeau Pharmaceuticals, Inc. Purified forms of rofecoxib, methods of manufacture and use
US11617735B2 (en) 2018-11-21 2023-04-04 Tremeau Pharmaceuticals, Inc. Purified forms of rofecoxib, methods of manufacture and use
JP7291220B2 (ja) 2018-11-21 2023-06-14 トレモ― ファーマシューティカルズ，インコーポレーテッド ロフェコキシブの精製形態、製造方法および使用
US11872206B2 (en) 2018-11-21 2024-01-16 Tremeau Pharmaceuticals, Inc. Purified forms of rofecoxib, methods of manufacture and use
US10945992B1 (en) 2019-11-13 2021-03-16 Tremeau Pharmaceuticals, Inc. Dosage forms of rofecoxib and related methods
US11858909B2 (en) 2021-04-09 2024-01-02 Tremeau Pharmaceuticals, Inc. Deuterated etoricoxib, methods of manufacture, and use thereof

Also Published As

Publication number Publication date
AU2003263582A1 (en) 2005-03-07

Similar Documents

Publication Publication Date Title
HU224840B1 (en) New process of preparing phenyl substituted 2(5h)-furanones having cox-2 inhibitor activity
JP2018523697A (ja) （４ｓ）−４−（４−シアノ−２−メトキシフェニル）−５−エトキシ−２，８−ジメチル−１，４−ジヒドロ−１，６−ナフチリジン−３−カルボキサミドの調製方法および電気化学的方法による（４ｓ）−４−（４−シアノ−２−メトキシフェニル）−５−エトキシ−２，８−ジメチル−１，４−ジヒドロ−１，６−ナフチリジン−３−カルボキサミドの回収
EP1270555B1 (fr) Procede d'oxydation d'un groupe thioether en groupe sulfoxyde
EP0377381B1 (fr) Procédé de préparation du phényl-1 diéthylaminocarbonyl-1 phtalimidométhyl-2 cyclopropane Z
HUE029282T2 (en) Methods for the preparation of 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide and its precursors
JPH06172281A (ja) ５−アミノレブリン酸のｎ−アシル誘導体、ならびに遊離の酸の塩酸塩の製造法
WO2005016906A1 (fr) Procede de fabrication de rofecoxibe
RU2676332C1 (ru) Способ получения 3-замещённых сложных эфиров (индол-1-ил)-уксусной кислоты
US5068458A (en) Chemical process for halogenating 2-methyl-6-methoxynaphthalene
EP1218366B8 (fr) Procede de preparation d'inhibiteurs cox-2
JP2021195344A (ja) ５−ブロモ−２−ハロゲン化安息香酸の製造方法
KR20000016043A (ko) Cox-２ 억제제로서 유용한 페닐 헤테로사이클의 제조방법
CN101624377A (zh) 一种合成瑞舒伐他汀钙关键中间体的方法
JP2989712B2 (ja) ベンゾピラン誘導体、その製法および血圧降下剤
CN117105891B (zh) 一种dbdmh促进的苯并呋喃类化合物的合成方法
JPS6028822B2 (ja) ４−メチルイミダゾ−ル−５−カルボン酸イソプロピルエステルの製法
JP2002255954A (ja) ２−ｎ−ブチル−５−ニトロベンゾフランの製造方法
TW200306304A (en) Process for the preparation of bicyclic diketone salts
LU83511A1 (fr) Procede de preparation d'acides dialuriques substitues en position 5
CN120208838A (zh) 一种艾瑞昔布及及其中间体的制备方法
JP3047582B2 (ja) トレオ−４−アルコキシ−５−（アリールヒドロキシメチル）−２（５ｈ）−フラノンの製造方法
US20040236103A1 (en) Methods for producing oxirane carboxylic acids and derivatives thereof
HUT61997A (en) Process for producing benzopyran derivatives, as well as antihypertensive and vasodilator pharmaceutical compositions comprising such compounds
WO2005023787A1 (fr) Procede d'elaboration de 2,1,3-benzoxadiazole-4-carboxaldehyde
FR2471978A1 (fr) Nouvelles oxazolines

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 KR 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 SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ 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