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WO1998056750A1 - Procede pour la preparation de diacereine - Google Patents

Procede pour la preparation de diacereine Download PDF

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Publication number
WO1998056750A1
WO1998056750A1 PCT/EP1998/003221 EP9803221W WO9856750A1 WO 1998056750 A1 WO1998056750 A1 WO 1998056750A1 EP 9803221 W EP9803221 W EP 9803221W WO 9856750 A1 WO9856750 A1 WO 9856750A1
Authority
WO
WIPO (PCT)
Prior art keywords
diacerein
acid
crude
process according
solution
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/EP1998/003221
Other languages
German (de)
English (en)
Inventor
Monica Sinistri
Roberta Sinistri
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.)
SYNTECO SpA
Original Assignee
SYNTECO SpA
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 SYNTECO SpA filed Critical SYNTECO SpA
Priority to AU85356/98A priority Critical patent/AU8535698A/en
Publication of WO1998056750A1 publication Critical patent/WO1998056750A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00—Systems containing at least three condensed rings

Definitions

  • the present invention relates to a process for the preparation of diacerein.
  • Diacerein or diacetylrein (1 ,8-diacetoxy-3- carboxyanthraquinone) is a known antiarthritic medicament used for some time in clinical practice.
  • FR-A-2508798 describes the acetylation of rein ( 1 , 8-dihydroxyanthraquinone-3- carboxylic acid), with an acetic anhydride excess in the presence of sulfuric acid.
  • EP-A-636602 discloses a preparation process characterized by purificating the crude diacerein by crystallization from 2-methoxyethanol or N,N- dimethylacetamide .
  • the methods described above, as well as other known ones, suffer anyway from some drawbacks (use of expensive, toxic solvents, difficulty of purification, unsatisfactory yields) which restrict its industrial use.
  • the purification step of crude diacerein is particularly critical.
  • the process of the invention comprises: a) acetylation of aloin, of formula (I): to give acetyl-barbaloin (II)
  • Step a) is preferably effected using acetic anhydride as acetylating agent.
  • the reaction is typically carried out using an acetic anhydride excess in the presence of bases such as potassium acetate, at a temperature of about 130°-140 ⁇ C.
  • Step b) is preferably carried out using chromic anhydride in acetic acid solution.
  • Chromic anhydride is used in excess to the stoichiometric, for example in molar ratios ranging from 5:1 to 10:1 compared with the starting aloin.
  • the reaction temperature usually ranges from 40 to 60°C.
  • the oxidation is preferably carried out without previous recovery of the compound (II).
  • step c) organic amines such as triethylamine, trimethylamine and the like can be used.
  • triethylamine in acetone solution is used, which is added to an acetone aqueous solution of crude diacerein.
  • the organic acid alkali salt is preferably 2-sodium ethylhexanoate , added in acetone/isopropanol solution.
  • the sodium salt is filtered, washed with acetone and dried.
  • Any organic or inorganic acid such as hydrochloric acid, sulfuric acid, acetic acid, p-toluenesulfonic acid, phosphoric acid, can be used for the conversion to acid diacerein.
  • Particularly preferred is the use of diluted phosphoric acid, at concentrations ranging from 1 to about 30%.
  • Example 1 illustrates the invention in greater detail.
  • a 1000 It reactor is loaded with 25 kg of aloin, 8.8 kg of anhydrous potassium acetate and 125 kg of acetic anhydride. The mixture is heated to 135°C, keeping said temperature for 60 minutes, after that is cooled to about 50 ⁇ C and added with 250 kg of acetic anhydride. Keeping the temperature at 55 ⁇ C, a solution of 30 kg of chromic anhydride dissolved in 100 kg of acetic acid is added in about 4 hours. At the end of the addition, temperature is kept at 55°C for 30 minutes, then 210 kg of water are added. After cooling at 15°C, the reaction mixture is centrifuged and washed to neutrality with water, finally dried at 70"C. The yield in crude diacerein is 15 kg with a K.F. lower than 0.5%.
  • a 1000 It reactor is loaded with 25 kg of aloin, 9 kg of anhydrous potassium acetate and 130 kg of acetic anhydride. The mixture is heated to 138 ⁇ C keeping said temperature for 60 minutes, after that is cooled to about 50°C and added with 260 kg of acetic anhydride. Temperature is brought to 45°C, then a solution of 31 kg of chromic anhydride dissolved in 105 1 of acetic acid is added in about 5 hours, keeping said temperature. At the end of the addition, temperature is kept for 30 minutes, then 220 kg of water are added. After cooling at 15°C, the reaction mixture is centrifuged, washing the cake with water to neutrality, then dried at 70°C. 15 kg of crude diacerein are obtained, having a 0.5% maximum K.F.

Landscapes

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

Abstract

L'invention concerne un procédé pour la préparation de diacéréine. Ce procédé se caractérise par la purification de diacéréine brute en la salifiant avec un sel alcalin d'acide organique avant d'effectuer une transformation en forme acide avec des acides dilués.
PCT/EP1998/003221 1997-06-11 1998-05-29 Procede pour la preparation de diacereine Ceased WO1998056750A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU85356/98A AU8535698A (en) 1997-06-11 1998-05-29 A process for the preparation of diacerein

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ITMI97A001375 1997-06-11
IT97MI001375A IT1292132B1 (it) 1997-06-11 1997-06-11 Procedimento per la preparazione di diacereina

Publications (1)

Publication Number Publication Date
WO1998056750A1 true WO1998056750A1 (fr) 1998-12-17

Family

ID=11377340

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1998/003221 Ceased WO1998056750A1 (fr) 1997-06-11 1998-05-29 Procede pour la preparation de diacereine

Country Status (3)

Country Link
AU (1) AU8535698A (fr)
IT (1) IT1292132B1 (fr)
WO (1) WO1998056750A1 (fr)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000068179A1 (fr) * 1999-05-07 2000-11-16 Synteco S.P.A. Purification de diacereine
WO2001044144A3 (fr) * 1999-12-17 2001-11-15 Ranbaxy Lab Ltd Procede de preparation de sels sodiques de statines
CN101696164A (zh) * 2009-10-19 2010-04-21 黄再新 一步法用芦荟甙合成双醋瑞因粗品的方法
WO2011030350A1 (fr) 2009-09-08 2011-03-17 Lupin Limited Procédé respectueux de l'environnement permettant l'oxydation catalytique par l'air de l'aloé-émodine en rheinal
EP2497761A1 (fr) 2011-02-11 2012-09-12 ICROM S.p.A. Un procédé de purification de composés anthraquinones
WO2011099834A3 (fr) * 2010-02-15 2013-01-03 Interquim, S.A. De C.V. Procédé de purification de diacéréine brute à l'aide de sel de potassium/diméthyl formamide
CN115521205A (zh) * 2022-09-22 2022-12-27 北京百奥药业有限责任公司 双醋瑞因钠盐的晶型及其制备方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0636602A1 (fr) * 1993-07-30 1995-02-01 Laboratoire Medidom S.A. Procédé de préparation de la diacérein
WO1996024572A1 (fr) * 1995-02-07 1996-08-15 Steba Beheer B.V. Procede de purification de la diacetylrheine

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0636602A1 (fr) * 1993-07-30 1995-02-01 Laboratoire Medidom S.A. Procédé de préparation de la diacérein
WO1996024572A1 (fr) * 1995-02-07 1996-08-15 Steba Beheer B.V. Procede de purification de la diacetylrheine

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000068179A1 (fr) * 1999-05-07 2000-11-16 Synteco S.P.A. Purification de diacereine
JP2002544183A (ja) * 1999-05-07 2002-12-24 シンテコ エッセ．ピ．ア． ジアセレインの精製方法
AU772845B2 (en) * 1999-05-07 2004-05-06 Synteco S.P.A. A process for the purification of diacerein
KR100700687B1 (ko) * 1999-05-07 2007-03-27 신테코 에스.피.아. 디아세레인 정제방법
WO2001044144A3 (fr) * 1999-12-17 2001-11-15 Ranbaxy Lab Ltd Procede de preparation de sels sodiques de statines
US6756507B2 (en) 1999-12-17 2004-06-29 Ranbaxy Laboratories Limited Process for the preparation of sodium salts of statins
WO2011030350A1 (fr) 2009-09-08 2011-03-17 Lupin Limited Procédé respectueux de l'environnement permettant l'oxydation catalytique par l'air de l'aloé-émodine en rheinal
CN101696164A (zh) * 2009-10-19 2010-04-21 黄再新 一步法用芦荟甙合成双醋瑞因粗品的方法
WO2011099834A3 (fr) * 2010-02-15 2013-01-03 Interquim, S.A. De C.V. Procédé de purification de diacéréine brute à l'aide de sel de potassium/diméthyl formamide
EP2497761A1 (fr) 2011-02-11 2012-09-12 ICROM S.p.A. Un procédé de purification de composés anthraquinones
CN115521205A (zh) * 2022-09-22 2022-12-27 北京百奥药业有限责任公司 双醋瑞因钠盐的晶型及其制备方法
CN115521205B (zh) * 2022-09-22 2023-11-10 北京百奥药业有限责任公司 双醋瑞因钠盐的晶型及其制备方法

Also Published As

Publication number Publication date
ITMI971375A0 (fr) 1997-06-11
AU8535698A (en) 1998-12-30
IT1292132B1 (it) 1999-01-25
ITMI971375A1 (it) 1998-12-11

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