WO2007129184A2 - Procédé amélioré de préparation de sodium de phénytoïne - Google Patents

Procédé amélioré de préparation de sodium de phénytoïne Download PDF

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Publication number
WO2007129184A2
WO2007129184A2 PCT/IB2007/001130 IB2007001130W WO2007129184A2 WO 2007129184 A2 WO2007129184 A2 WO 2007129184A2 IB 2007001130 W IB2007001130 W IB 2007001130W WO 2007129184 A2 WO2007129184 A2 WO 2007129184A2
Authority
WO
WIPO (PCT)
Prior art keywords
phenytoin
sodium
water
preparation
dissolved
Prior art date
Application number
PCT/IB2007/001130
Other languages
English (en)
Other versions
WO2007129184A3 (fr
Inventor
Siripragada Mahender Rao
Padmanabhan Ramar
Original Assignee
Orchid Chemicals & Pharmaceuticals Limited
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 Orchid Chemicals & Pharmaceuticals Limited filed Critical Orchid Chemicals & Pharmaceuticals Limited
Publication of WO2007129184A2 publication Critical patent/WO2007129184A2/fr
Publication of WO2007129184A3 publication Critical patent/WO2007129184A3/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two 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
    • C07D233/72—Two oxygen atoms, e.g. hydantoin
    • C07D233/74—Two oxygen atoms, e.g. hydantoin with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to other ring members

Definitions

  • the present invention relates to an improved process for the preparation of Phenytoin Sodium, a sodium channel blocker used for the treatment of epilepsy.
  • Phenytoin Sodium which is chemically known as 5,5-Diphenylhydantoin sodium salt is a sodium channel blocker, and has the following structural formula:
  • Phenytoin Sodium is a well-known pharmaceutical agent having anticonvulsant and antiepileptic activity and useful in the treatment of epilepsy and it is available in the market under the various brand names such as Aleviatin ® , Persantin ® , Aurantin ® , Dilantin ® , Dintoina ® , Epanutin ® etc.
  • US Pat. No. 3,646,056 describes a process for the preparation of 5,5-diarylhydantoins in one step by reacting benzoin with 1-3 equivalents of urea in an alkaline medium in the presence of 0.5-4 equivalents of elemental sulfur at a temperature between 60° C and the boiling point of the reaction mixture.
  • US Pat. No. 6,245,917 teaches a process for the preparation of crystalline sodium phenytoin monohydrate by mixing sodium Phenytoin anhydrate and water in an organic solvent selected from toluene, methanol and dichloromethane, at about 30 0 C to about 40 0 C.
  • the main objective of the present invention is to provide an improved process for the preparation of compound of formula (I) in high yield and high purity.
  • Another objective of the present invention is to provide a process for the preparation of compound of formula (I), which uses water as a solvent and avoids organic solvents.
  • Another objective of the present invention is to provide a process for the preparation of compound of formula (I), which is economical and commercially viable.
  • the present invention provides a process for the preparation of Phenytoin Sodium (I), by reacting of Phenytoin of formula (II) with aqueous solution of sodium hydroxide in presence of aqueous Sodium chloride using water as a solvent at a temperature of about 25° C to 50° C to obtain Phenytoin Sodium of formula (I).
  • the aqueous sodium chloride is used in different concentration with respect to Phenytoin where the concentration varies from 10 to 50% preferably 20 to 40%.
  • the reaction is performed at a temperature of about 5° C to 50° C. Most preferably; the reaction step is performed at a temperature of about 5° C to 30° C.
  • the starting material of this invention is prepared according to the literature available in the prior art.
  • Phenytoin (2Og) was dissolved in 120 mL of DM water and Sodium hydroxide solution (3.56g dissolved in water 22.5mL) at 25-30 0 C in a 250 mL four-necked RBF. The reaction mixture was filtered and the clear filtrate was collected. The reaction mass was cooled to 5-10 0 C under nitrogen atmosphere and stirred for 60min. The solid was filtered under vacuum & nitrogen atmosphere and washed the product with 2OmL of chilled water. The solid was dried at 50-60 0 C under nitrogen atmosphere to obtain 14.4g of dry Phenytoin sodium. Yield: approx. 66.2% w.r.t. Phenytoin
  • Phenytoin (2Og) was dissolved in 120 mL of DM water and Sodium hydroxide solution (3.56g dissolved in water 22.5mL) at 25-30 0 C in a 250 mL four-necked RBF. The reaction mixture was filtered and the clear filtrate was collected and Sodium chloride solution (4g Dissolved in water 1OmL) was added to it. The reaction mass was cooled to 5-10 0 C under nitrogen atmosphere and stirred for 60min. The solid was filtered under vacuum & nitrogen atmosphere and washed the product with 2OmL of chilled water. The solid was dried at 50-60 0 C under nitrogen atmosphere to obtain 18.5g of dry Phenytoin sodium. Yield : approx. 85% w.r.t. Phenytoin
  • Phenytoin (25g) was dissolved in 150 mL of DM water and Sodium hydroxide solution (4.45g dissolved in water 25mL) at 25-30 0 C in a 250 mL four-necked RBF. The reaction mixture was filtered and the clear filtrate was collected and Sodium chloride solution (7.5g Dissolved in water 22mL) was added to it. The reaction mass was cooled to 5-10 0 C under nitrogen atmosphere and stirred for 60min. The solid was filtered under vacuum & nitrogen atmosphere and washed the product with 2OmL of chilled water. The solid was dried at 50-60 0 C under nitrogen atmosphere to obtain 25.3g of dry Phenytoin sodium. Yield : approx. 93% w.r.t. Phenytoin
  • Phenytoin (25g) was dissolved in 150 mL of DM water and Sodium hydroxide solution (4.45g dissolved in water 25mL) at 25-30 0 C in a 250 mL four-necked RBF. The reaction mixture was filtered and the clear filtrate was collected and Sodium chloride solution (1Og Dissolved in water 28mL) was added to it. The reaction mass was cooled to 5-10 0 C under nitrogen atmosphere and stirred for 60min. The solid was filtered under vacuum & nitrogen atmosphere and washed the product with 2OmL of chilled water. The solid was dried at 50-60 0 C under nitrogen atmosphere to obtain 25.9g of dry Phenytoin sodium. Yield: approx. 95.3% w.r.t. Phenytoin
  • Phenytoin (178g) was dissolved in 600 mL of DM water and Sodium hydroxide solution (16.7g dissolved in water 105mL) at 30-40 0 C in a 2 L RBF. The reaction mixture was filtered and the clear filtrate was collected and Sodium chloride solution (2 Ig dissolved in water 32mL) was added to it. The filtrate was cooled to 5-10 0 C under nitrogen atmosphere and stirred for 60min. The solid was filtered under vacuum & nitrogen atmosphere and washed with 10OmL of chilled water. The solid was dried at 50-60 0 C under nitrogen atmosphere to obtain 102.6g of dry Phenytoin sodium.

Landscapes

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

Abstract

L'invention concerne un procédé amélioré de préparation de sodium de phénytoïne de formule (I). Ce procédé consiste à faire réagir de la phénytoïne avec une solution aqueuse d'hydroxyde de sodium en présence de chlorure de sodium aqueux.
PCT/IB2007/001130 2006-05-04 2007-05-02 Procédé amélioré de préparation de sodium de phénytoïne WO2007129184A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN806/CHE/2006 2006-05-04
IN806CH2006 2006-05-04

Publications (2)

Publication Number Publication Date
WO2007129184A2 true WO2007129184A2 (fr) 2007-11-15
WO2007129184A3 WO2007129184A3 (fr) 2009-06-04

Family

ID=38668137

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2007/001130 WO2007129184A2 (fr) 2006-05-04 2007-05-02 Procédé amélioré de préparation de sodium de phénytoïne

Country Status (1)

Country Link
WO (1) WO2007129184A2 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109456271A (zh) * 2018-11-20 2019-03-12 宁波职业技术学院 一种苯妥英钠的合成方法
CN111978258A (zh) * 2020-08-13 2020-11-24 山西新宝源制药有限公司 制备苯妥英钠的方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6245917B1 (en) * 1998-03-20 2001-06-12 Warner-Lambert Company Crystalline sodium phenytoin monohydrate

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6245917B1 (en) * 1998-03-20 2001-06-12 Warner-Lambert Company Crystalline sodium phenytoin monohydrate

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
NI, N. ET AL.: 'Estimation of the effect of NaCl on the solubility of organic compounds in aqueous solutions' JOURNAL OF PHARMACEUTICAL SCIENCES vol. 89, no. ISS.12, 17 October 2000, ISSN 0022-3549 pages 1620 - 1625 *
SWABRICK, J ET AL. ENCYCLOPEDIA OF PHARMACEUTICAL TECHNOLOGY, [Online] vol. 20, no. SUPPLE, 2001, page 500 ISBN: 082472819X Retrieved from the Internet: <URL:http://books.google.com/books?id=gJYv8 mdG0iEC8&pg=PP1&dq= Encyclopedia+of+Pharmaceutical+Technology:+ Volume+20+- +Supplement+3&client=firefox-a> *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109456271A (zh) * 2018-11-20 2019-03-12 宁波职业技术学院 一种苯妥英钠的合成方法
CN109456271B (zh) * 2018-11-20 2022-06-21 宁波职业技术学院 一种苯妥英钠的合成方法
CN111978258A (zh) * 2020-08-13 2020-11-24 山西新宝源制药有限公司 制备苯妥英钠的方法

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Publication number Publication date
WO2007129184A3 (fr) 2009-06-04

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