WO2004050663A2 - Procede ameliore de preparation de cefuroxime sodique - Google Patents

Procede ameliore de preparation de cefuroxime sodique Download PDF

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Publication number
WO2004050663A2
WO2004050663A2 PCT/IB2003/005563 IB0305563W WO2004050663A2 WO 2004050663 A2 WO2004050663 A2 WO 2004050663A2 IB 0305563 W IB0305563 W IB 0305563W WO 2004050663 A2 WO2004050663 A2 WO 2004050663A2
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WO
WIPO (PCT)
Prior art keywords
formula
sodium
acid
cefuroxime
water
Prior art date
Application number
PCT/IB2003/005563
Other languages
English (en)
Other versions
WO2004050663A3 (fr
Inventor
Pandurang Balwant Deshpande
Pramod Narayan Deshpande
Bhausaheb Pandharinath Khadangale
Gautam Kumar Das
John Muthiah Raja Jeyakumar
Original Assignee
Orchid Chemicals & Pharmaceuticals 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
Priority claimed from US10/310,068 external-priority patent/US20040092735A1/en
Application filed by Orchid Chemicals & Pharmaceuticals Ltd filed Critical Orchid Chemicals & Pharmaceuticals Ltd
Priority to AU2003283660A priority Critical patent/AU2003283660A1/en
Publication of WO2004050663A2 publication Critical patent/WO2004050663A2/fr
Publication of WO2004050663A3 publication Critical patent/WO2004050663A3/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring

Definitions

  • the present invention relates to an improved process for the preparation of active cephalosporin antibiotic derivative.
  • the present invention more particularly relates to an improved process for the preparation of cefuroxime sodium of the formula (I).
  • Cefuroxime is a valuable broad spectrum antibiotic and having activity against wide range of gram-positive and gram-negative microorganisms.
  • Cefuroxime sodium is physiologically acceptable non- toxic salt of cefuroxime and may be administered to human or used as a veterinary medicine.
  • the preparation involves the condensation of 3-hydroxymethyl-7-amino cephalosporanic acid with (fur-2-yl)-2-methoxyimino acetic acid to produce (6R,7R)-7-[(Z)-2-(fur-2-yl)-2- methoxyiminoacetamido]-3-hydroxymethylceph-3-em-4-carboxylic acid.
  • US patent 4,775,750 discloses the process for the preparation of the compound of formula (I), which involves carbamoylation of (6R,7R)-7-[Z-2-(fur- 2-yl)-2-methoxyiminoacetamido]-3-hydroxymethylceph-3-em-4-carboxylic acid, and in situ preparation of cefuroxime sodium using sodium-2-ethylhexanote.
  • the product obtained from this patent suffers in non-acceptable color and low purity. Reprocessing is needed to get sterile cefuroxime sodium.
  • US patent 4,277,601 describes the process for the preparation of cefuroxime sodium as its THF solvate in situ manner. The process described in this patent involves the usage of multiple organic solvent systems and thereby making the process complicated.
  • WO 00/71547 describes a process for the preparation of cefuroxime, which involves enzymatic hydrolysis of 7-glutaryl ACA, which is not industrially viable.
  • cefuroxime sodium With our continued search and intense investigation, we finally achieved a process for the preparation cefuroxime sodium, which overcomes all difficulties and makes the process industrially viable and yield the title compound in required quantity and quality.
  • the main objective of the present invention is to provide a process for the preparation of cefuroxime sodium of the formula (I), which has better quality such as color and solubility.
  • Another objective of the present invention is to provide direct manufacturing process for the preparation of sterile crystalline cefuroxime sodium of the formula (I) from cefuroxime acid.
  • Still another objective of the present invention is to provide a process for the preparation of cefuroxime sodium of the formula (I) in good yield, high purity and with desirable particle size.
  • Yet another objective of the present invention is to provide a simple method for the preparation of cefuroxime of the formula (II) in pure form.
  • the present invention provides an improved process for the preparation of cefuroxime sodium of the formula (I),
  • Another embodiment of the present invention is to provide a process for the preparation of cefuroxime of the formula (II), which comprises the steps of:
  • cefuroxime of formula (II) was dissolved in water miscible solvent /water such as acetone, THF, acetonitrile, alcohols like methanol, ethanol at a temperature in the range of 10°C to 50°C.
  • water miscible solvent /water such as acetone, THF, acetonitrile, alcohols like methanol, ethanol at a temperature in the range of 10°C to 50°C.
  • the mixture of water soluble sodium salt of weak acid is selected from sodium lactate/sodium acetate, sodium 2-ethyl hexonate/sodium acetate and the like.
  • the reaction may be carried out in an alcoholic solvent selected from methanol, ethanol, isopropyl alcohol or mixtures thereof, at a temperature in the range of 10°C to 50°C.
  • the compound of formula (I) was isolated from reaction mass by adding suitable water miscible solvent such as acetone, methanol, ethanol, isopropyl alcohol or mixtures thereof.
  • the isolated mass was washed with solvents such as acetone, methanol, ethyl acetate, isopropyl ether, hexane, diethyl ether, toluene and the like or mixtures thereof.
  • solvents such as acetone, methanol, ethyl acetate, isopropyl ether, hexane, diethyl ether, toluene and the like or mixtures thereof.
  • 7-amino cephalosporanic acid of formula (III) was dissolved in solvents such as methanol, acetone, dichloromethane, THF, water or mixtures thereof, to that sodium hydroxide solution was added at a temperature in the range of -90°C to 0°C, to produce compound of formula (IV).
  • the activation of fur-2- yl methoxyimino acetic acid of formula (V) is carried out using PC1 5 , DMF/POCl 3 , oxalyl chloride, SOCl 2 /DMF, diphenylchlorophosphoridate, dialkyl chlorophosphoridate, in the presence of a solvent selected from halogenated alkanes, ethyl acetate, tetrahydrofuran, aromatic hydrocarbons, acetone, acetonitrile, dialkyl ethers or mixtures thereof at a temperature in the range of -40°C to 10°C.
  • a solvent selected from halogenated alkanes, ethyl acetate, tetrahydrofuran, aromatic hydrocarbons, acetone, acetonitrile, dialkyl ethers or mixtures thereof at a temperature in the range of -40°C to 10°C.
  • the compound of formula (IV) was reacted with the active derivative of fur-2-yl methoxyimino acetic acid ammonium salt of formula (V), in the presence of inorganic base such as sodium bicarbonate, sodium hydroxide, potassium carbonate and sodium carbonate in the presence of solvents such as methanol, acetone, dichloromethane, THF, water or mixtures thereof to produce the compound of formula (VI).
  • inorganic base such as sodium bicarbonate, sodium hydroxide, potassium carbonate and sodium carbonate
  • solvents such as methanol, acetone, dichloromethane, THF, water or mixtures thereof
  • the acid used for adjusting pH in step (i) is selected from hydrochloric acid, sulphuric acid or ortho phosphoric acid.
  • the labile group represented by R is selected from chlorosulphonyl, mono, di or trichloroacetyl, bromosulphonyl, trichloroethoxycarbonyl, trimethylsilyl or chlorobenzene sulphonyl group.
  • the compound of formula (VI) was reacted with the compound of formula (VII) to produce the compound of formula (II), in the presence of a solvent selected from THF, methanol dichloromethane, acetone, water or mixtures thereof.
  • the cefuroxime sodium of the formula (I) obtained is sterile crystalline syn isomer.
  • reaction mass was washed with ethyl acetate and then aqueous layer was subjected to charcoal treatment.
  • the pH of aqueous solution was adjusted to 2.0 using dilute HC1.
  • the product formed was filtered and washed with water followed by isopropyl alcohol to produce the title compound of formula (II) (105 gm).
  • non-polar solvent like IPE, toluene cyclohexane, and the like helps in changing the nature of the slurry substantially, hence it is easy to filter the solid.

Abstract

L'invention concerne un procédé amélioré de préparation de céfuroxime sodique stérile représenté par la formule (I).
PCT/IB2003/005563 2002-12-05 2003-12-03 Procede ameliore de preparation de cefuroxime sodique WO2004050663A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2003283660A AU2003283660A1 (en) 2002-12-05 2003-12-03 An improved process for the preparation of cefuroxime sodium

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US10/310,068 US20040092735A1 (en) 2002-11-08 2002-12-05 Process for the preparation of cefuroxime sodium
US10/310,068 2002-12-05
IN219/MAS/2003 2003-03-17
IN219CH2003 2003-03-17

Publications (2)

Publication Number Publication Date
WO2004050663A2 true WO2004050663A2 (fr) 2004-06-17
WO2004050663A3 WO2004050663A3 (fr) 2004-10-28

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Country Link
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Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008132574A1 (fr) * 2007-04-27 2008-11-06 Parabolic Drugs Limited Purification de l'acide céfuroxime
WO2008155615A2 (fr) * 2007-06-18 2008-12-24 Orchid Chemicals & Pharmaceuticals Limited Procédé perfectionné pour la préparation d'un antibiotique de la famille des céphalosporines
CN101967156A (zh) * 2010-09-26 2011-02-09 石药集团石家庄高科医药科技开发有限公司 一种头孢呋辛钠重结晶的方法
CN101475579B (zh) * 2009-01-20 2011-02-09 广州白云山天心制药股份有限公司 一种稳定的头孢呋辛钠及其制备方法
CN102070572A (zh) * 2010-12-17 2011-05-25 山东金城医药化工股份有限公司 一种从呋喃铵盐废渣中回收制备呋喃酮酸的方法
CN102295653A (zh) * 2010-06-28 2011-12-28 广州白云山制药股份有限公司广州白云山化学制药厂 头孢呋辛钠的一步法回收制备方法
CN102702231A (zh) * 2012-06-18 2012-10-03 山东大学 一种3-去氨甲酰基-头孢呋辛酸的制备方法
CN103044452A (zh) * 2013-01-10 2013-04-17 潘行远 一种低水分、高稳定性的无菌头孢呋辛钠的制备方法
CN103102357A (zh) * 2013-02-21 2013-05-15 广东立国制药有限公司 一种头孢呋辛钠的合成方法
CN103819490A (zh) * 2014-03-20 2014-05-28 悦康药业集团有限公司 一种头孢呋辛钠化合物
CN104910187A (zh) * 2015-05-28 2015-09-16 浙江长典医药有限公司 一种小儿用头孢呋辛钠化合物实体及其制剂
CN105440055A (zh) * 2015-12-30 2016-03-30 中山市金城道勃法制药有限公司 一种原研制品质头孢呋辛酸及其药物制剂
CN108440568A (zh) * 2018-04-11 2018-08-24 广东立国制药有限公司 一种去氨甲酰基头孢呋辛的制备方法
CN109988183A (zh) * 2019-04-17 2019-07-09 广东立国制药有限公司 一种头孢呋辛酸的中间体的环保制备方法
CN112480146A (zh) * 2020-10-30 2021-03-12 浙江惠迪森药业有限公司 一种头孢呋辛酸混合溶剂化物、晶型及制备方法
WO2021232694A1 (fr) * 2020-05-22 2021-11-25 山东金城柯瑞化学有限公司 Procédé de synthèse catalytique à base de nickel de l'acide 3-décarbamoylcéfuroxime
WO2023050596A1 (fr) * 2021-09-30 2023-04-06 海南海灵化学制药有限公司 Procédé de préparation de céfuroxime sodique pour injection

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1453049A (en) * 1973-08-21 1976-10-20 Glaxo Lab Ltd Cephalosporing antibiotics
US4277601A (en) * 1979-02-15 1981-07-07 Glaxo Group Limited Preparation of sodium cefuroxime
US4284767A (en) * 1978-04-07 1981-08-18 Glaxo Group Limited Process for preparing 3-carbamoyloxymethyl cephalosporins
US4775750A (en) * 1983-07-29 1988-10-04 Glaxo Group Limited Process for preparing sodium cefuroxime
WO2002020532A1 (fr) * 2000-09-11 2002-03-14 Biochemie Gesellschaft M.B.H. Intermediaires dans la production de cephalosporine

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1453049A (en) * 1973-08-21 1976-10-20 Glaxo Lab Ltd Cephalosporing antibiotics
US4284767A (en) * 1978-04-07 1981-08-18 Glaxo Group Limited Process for preparing 3-carbamoyloxymethyl cephalosporins
US4277601A (en) * 1979-02-15 1981-07-07 Glaxo Group Limited Preparation of sodium cefuroxime
US4775750A (en) * 1983-07-29 1988-10-04 Glaxo Group Limited Process for preparing sodium cefuroxime
WO2002020532A1 (fr) * 2000-09-11 2002-03-14 Biochemie Gesellschaft M.B.H. Intermediaires dans la production de cephalosporine

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
WILSON, E. M.: "A tale of two cephalosporins." CHEMISTRY AND INDUSTRY, 1984, pages 217-221, XP0001180706 cited in the application *

Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008132574A1 (fr) * 2007-04-27 2008-11-06 Parabolic Drugs Limited Purification de l'acide céfuroxime
WO2008155615A2 (fr) * 2007-06-18 2008-12-24 Orchid Chemicals & Pharmaceuticals Limited Procédé perfectionné pour la préparation d'un antibiotique de la famille des céphalosporines
WO2008155615A3 (fr) * 2007-06-18 2009-02-19 Orchid Chemicals & Pharm Ltd Procédé perfectionné pour la préparation d'un antibiotique de la famille des céphalosporines
CN101475579B (zh) * 2009-01-20 2011-02-09 广州白云山天心制药股份有限公司 一种稳定的头孢呋辛钠及其制备方法
CN102295653A (zh) * 2010-06-28 2011-12-28 广州白云山制药股份有限公司广州白云山化学制药厂 头孢呋辛钠的一步法回收制备方法
CN101967156A (zh) * 2010-09-26 2011-02-09 石药集团石家庄高科医药科技开发有限公司 一种头孢呋辛钠重结晶的方法
CN102070572A (zh) * 2010-12-17 2011-05-25 山东金城医药化工股份有限公司 一种从呋喃铵盐废渣中回收制备呋喃酮酸的方法
CN102702231A (zh) * 2012-06-18 2012-10-03 山东大学 一种3-去氨甲酰基-头孢呋辛酸的制备方法
CN102702231B (zh) * 2012-06-18 2014-10-29 山东大学 一种3-去氨甲酰基-头孢呋辛酸的制备方法
CN103044452A (zh) * 2013-01-10 2013-04-17 潘行远 一种低水分、高稳定性的无菌头孢呋辛钠的制备方法
CN103102357B (zh) * 2013-02-21 2016-01-13 广东立国制药有限公司 一种头孢呋辛钠的合成方法
CN103102357A (zh) * 2013-02-21 2013-05-15 广东立国制药有限公司 一种头孢呋辛钠的合成方法
CN103819490A (zh) * 2014-03-20 2014-05-28 悦康药业集团有限公司 一种头孢呋辛钠化合物
CN103819490B (zh) * 2014-03-20 2016-03-30 悦康药业集团有限公司 一种头孢呋辛钠化合物
CN104910187A (zh) * 2015-05-28 2015-09-16 浙江长典医药有限公司 一种小儿用头孢呋辛钠化合物实体及其制剂
CN105440055A (zh) * 2015-12-30 2016-03-30 中山市金城道勃法制药有限公司 一种原研制品质头孢呋辛酸及其药物制剂
CN108440568A (zh) * 2018-04-11 2018-08-24 广东立国制药有限公司 一种去氨甲酰基头孢呋辛的制备方法
CN109988183A (zh) * 2019-04-17 2019-07-09 广东立国制药有限公司 一种头孢呋辛酸的中间体的环保制备方法
WO2021232694A1 (fr) * 2020-05-22 2021-11-25 山东金城柯瑞化学有限公司 Procédé de synthèse catalytique à base de nickel de l'acide 3-décarbamoylcéfuroxime
CN112480146A (zh) * 2020-10-30 2021-03-12 浙江惠迪森药业有限公司 一种头孢呋辛酸混合溶剂化物、晶型及制备方法
WO2023050596A1 (fr) * 2021-09-30 2023-04-06 海南海灵化学制药有限公司 Procédé de préparation de céfuroxime sodique pour injection

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