EP0000678B1 - Synthesezwischenprodukt: Glycerylanthranilat und Verfahren zur Herstellung desselben - Google Patents

Synthesezwischenprodukt: Glycerylanthranilat und Verfahren zur Herstellung desselben Download PDF

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Publication number
EP0000678B1
EP0000678B1 EP19780400059 EP78400059A EP0000678B1 EP 0000678 B1 EP0000678 B1 EP 0000678B1 EP 19780400059 EP19780400059 EP 19780400059 EP 78400059 A EP78400059 A EP 78400059A EP 0000678 B1 EP0000678 B1 EP 0000678B1
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EP
European Patent Office
Prior art keywords
compound
glycerol
preparation
synthesis
condensation catalyst
Prior art date
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Expired
Application number
EP19780400059
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English (en)
French (fr)
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EP0000678A1 (de
Inventor
Gilbert Dr. Mouzin
Henri Dr. Cousse
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.)
Pierre Fabre SA
Original Assignee
Pierre Fabre SA
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Filing date
Publication date
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Application filed by Pierre Fabre SA filed Critical Pierre Fabre SA
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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D215/38—Nitrogen atoms
    • C07D215/42—Nitrogen atoms attached in position 4
    • C07D215/44—Nitrogen atoms attached in position 4 with aryl radicals attached to said nitrogen atoms

Definitions

  • the present invention carried out at the Pierre FABRE Research Center, relates to a new derivative of anthranilic acid and its preparation process.
  • the invention relates to a derivative of formula: ⁇ -glyceryl anthranilate and its salts, in particular its halohydrates, which are useful in particular as synthetic intermediates for preparing medicaments.
  • this new derivative can be obtained by condensation of glycerol on isatoic anhydride according to the following reaction scheme:
  • condensation catalyst in particular a base, which can be mineral, for example an alkali or alkaline earth metal hydroxide, or organic, for example triethylamine. Soda is preferably used as the condensation catalyst.
  • reaction temperature and pressure are not very critical parameters, nevertheless, taking into account in particular the gas evolution which occurs, it is advantageous to eliminate the gas formed by continuous pumping, to heat the reaction mixture only enough slowly and maintain for some time, for example 1 hour, the reaction mixture at a temperature between 60 and 90 ° C.
  • the reaction is carried out in the presence of a molar excess of glycerol which serves as solvent and improves the yield of the reaction, this molar excess can be understood, for example, between 2/1 and 20/1 compared to isatoic anhydride .
  • the process according to the invention makes it possible to obtain ⁇ -glyceryl anthranilate in solution in glycerol which can be used as it is in other reaction stages.
  • the raw product can be separated by one of the many processes known in the chemical industry.
  • the crude product can also be purified by crystallization from the hydrochloride.
  • A-glyceryl anthranilate is an intermediate product in the synthesis of derivatives of the 4- (2'-carboxyphenylamino) -7-chloroquinoline or glafenine type which is a known analgesic compound.
  • This process for the preparation of glafenine has the advantage of using only products widely available commercially and inexpensively.
  • isatoic anhydride which is experiencing industrial development as a synthesis intermediary in the dye industry can, thanks to new synthesis processes, be obtained at prices much lower than the prices of anthranilic acid which constitutes the basic product in known syntheses of glafenine.
  • this synthetic method makes it possible to significantly increase the yields of glafenine compared to known methods such as the method described in French patent 1,421,229 which uses the acetonide of the compound according to the present invention as synthesis intermediate, in particular limiting the number of reaction steps.
  • Example 1 The solution obtained in Example 1 is treated to remove the excess glycerol, the reaction residue is diluted in ethyl acetate then hydrochloride, either by bubbling gaseous hydrochloric acid, or by adding ethanol saturated with hydrochloric acid.
  • the glyceryl anthranilate hydrochloride is crystallized after concentration of the solvents and addition of methylal.

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

Claims (8)

1. Verbindung der Formel
Figure imgb0011
und deren Salze.
2. Verbindung nach Anspruch 1 in Form des Chlorhydrats.
3. Verfahren zur Herstellung einer Verbindung gemäß Formel
Figure imgb0012
in lösung in Glyzerin, dadurch gekennzeichnet, daß man das Glyzerin mit Isatoicsäureanhydrid gemäß Formel
Figure imgb0013
in Gegenwart eines Kondensationskatalysators kondensiert, wobei man einen molaren Überschuß Glyzerin, bezogen auf das Isatoicsäureanhydrid, verwendet.
4. Verfahren nach Anspruch 3, dadurch gekennzeichnet, daß man als Kondensationskatalysator eine organische oder eine Mineralbase verwendet.
5. Verfahren nach Anspruch 4, dadurch gekennzeichnet, daß man als Kondensationskatalysator ein Alkalimetall- oder Erdalkalimetallhydroxid verwendet.
6. Verfahren nach Anspruch 5, dadurch gekennzeichnet, daß man als Kondensationskatalysator Natriumkarbonat (Soda) verwendet.
7. Verfahren nach einem der Ansprüche 3 bis 6, dadurch gekennzeichnet, daß man das Glyzerin, bezogen auf das Isatinsäureanhydrid, in molarem Überschuß von 2:1 bis 20:1 verwendet.
8. Verwendung der Verbindung nach einem der Ansprüche 12 und/oder 2, als Zwischenprodukt bei der Synthese von Glafeninum durch Umsetzung dieser Verbindung mit 4,7-Dichlorchinolin.
EP19780400059 1977-07-26 1978-07-18 Synthesezwischenprodukt: Glycerylanthranilat und Verfahren zur Herstellung desselben Expired EP0000678B1 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR7722899A FR2398719A1 (fr) 1977-07-26 1977-07-26 Nouvel intermediaire de synthese : l'anthranilate de glyceryle et son procede de preparation
FR7722899 1977-07-26

Publications (2)

Publication Number Publication Date
EP0000678A1 EP0000678A1 (de) 1979-02-07
EP0000678B1 true EP0000678B1 (de) 1981-08-05

Family

ID=9193811

Family Applications (1)

Application Number Title Priority Date Filing Date
EP19780400059 Expired EP0000678B1 (de) 1977-07-26 1978-07-18 Synthesezwischenprodukt: Glycerylanthranilat und Verfahren zur Herstellung desselben

Country Status (4)

Country Link
EP (1) EP0000678B1 (de)
DE (1) DE2860897D1 (de)
ES (1) ES472071A1 (de)
FR (1) FR2398719A1 (de)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2843037B1 (fr) 2002-08-01 2006-01-27 Salomon Sa Ensemble de retenue d'une chaussure sur une planche de glisse

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3123631A (en) * 1964-03-03 Process for preparing esters of
FR1421229A (fr) * 1962-08-20 1965-12-17 Roussel Uclaf Nouveau dérivé de la quinoléine et procédé de préparation

Also Published As

Publication number Publication date
ES472071A1 (es) 1979-03-16
FR2398719A1 (fr) 1979-02-23
FR2398719B1 (de) 1980-10-10
DE2860897D1 (en) 1981-11-05
EP0000678A1 (de) 1979-02-07

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