CH670632A5 - Prodn. of antiinflammatory 4-naphthyl-2-butanone deriv. - Google Patents

Prodn. of antiinflammatory 4-naphthyl-2-butanone deriv. Download PDF

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CH670632A5
CH670632A5 CH54087A CH54087A CH670632A5 CH 670632 A5 CH670632 A5 CH 670632A5 CH 54087 A CH54087 A CH 54087A CH 54087 A CH54087 A CH 54087A CH 670632 A5 CH670632 A5 CH 670632A5
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formula
reaction
compound
naphthyl
organometallic reagent
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CH54087A
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German (de)
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Richard Vaughan Davies
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Beecham Group Plc
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/20—Unsaturated compounds containing keto groups bound to acyclic carbon atoms
    • C07C49/255—Unsaturated compounds containing keto groups bound to acyclic carbon atoms containing ether groups, groups, groups, or groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/51—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition
    • C07C45/511—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition involving transformation of singly bound oxygen functional groups to >C = O groups
    • C07C45/515—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition involving transformation of singly bound oxygen functional groups to >C = O groups the singly bound functional group being an acetalised, ketalised hemi-acetalised, or hemi-ketalised hydroxyl group
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/51—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition
    • C07C45/518—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition involving transformation of sulfur-containing compounds to >C = O groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/56—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds
    • C07C45/567—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with sulfur as the only hetero atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/56—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds
    • C07C45/57—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with oxygen as the only heteroatom
    • C07C45/59—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with oxygen as the only heteroatom in five-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/56—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds
    • C07C45/57—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with oxygen as the only heteroatom
    • C07C45/60—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with oxygen as the only heteroatom in six-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

Prodn. of 4-(6-methoxy- 2-naphthyl)- 2-butanone (I) is effected by converting a 2-halo- 6-methoxynaphthalene of formula (II) to an organometallic deriv., reacting this with an opt. protected 2-butanone deriv of formula QCH2CH2CXCH3 (III) and removing any protecting gp. In the formulae, Y=halogen; Q=a leaving gp; CX=opt. protected CO. Pref Q=halogen, 1-4C alkanoyloxy, tosyloxy, nesyloxy, triflate, phosphonium, sulphonium or trialkylammonium; X=diethoxy, dimethylthio, ethylenedioxy, propylenedioxy or ethylenedithio.

Description

       

  
 



   BESCHREIBUNG



   Diese Erfindung bezieht sich auf ein neues Verfahren zur Herstellung von   4-(6-Methoxy-2-naphthyl)-butan-2-on.   



   Die US-Patentschrift 4 061 779 beschreibt 4-(6-Methoxy2-naphthyl)-butan-2-on (Nabumetone) und seine Verwendung bei der Behandlung von rheumatischen und arthritischen Affektionen. Eine Anzahl von Verfahren zur Herstellung der Verbindung werden ebenfalls beschrieben. Die US Patentschriften 4 221 741 und 4 247 709 beschreiben weitere Verfahren zur Herstellung von Nabumetone.



   Ein weiteres Verfahren zur Herstellung von Nabumetone wurde nun erfunden, das durch eine Alkylierung von 2-Methoxynaphthalin in der 6-Stellung gekennzeichnet ist.



   Demgemäss bezieht sich die vorliegende Erfindung auf ein Verfahren zur Herstellung von 4-(6-Methoxy-2-naphthyl)-butan-2-on, das gekennzeichnet ist durch die Reaktion eines metallorganischen Reagens, das von einer Verbindung der Formel (I):
EMI1.6     
 worin Hal Halogen ist, abgeleitet ist, mit einer Verbindung der Formel   (II):   
EMI1.7     
   worin Q eine Abgangsgruppe ist und C = X eine gegebenen-    falls geschützte Carbonylgruppe ist, und anschliessende Entfernung der Schutzgruppe von C=X, wenn dieses eine geschützte Carbonylgruppe darstellt.



   Geeignete Bedeutungen von Hal in Formel (I) umfassen Iod, Brom, Chor und Fluor, vorzugsweise Brom.



   Geeignete Beispiele von metallorganischen Reagentien, die von einer Verbindung der Formel (I) abgeleitet sind, umfassen Grignardreagentien und lithiumorganische Verbindungen, die mittels herkömmlicher Methoden hergestellt sind. Vorteilhafterweise entspricht das metallorganische Reagens der Formel (III):
EMI1.8     

Q ist eine Gruppe, die leicht durch Nukleophile ersetzt wird. Beispiele derartiger Gruppen umfassen Halogen, wie Chlor, Brom und Iod, Acyloxy, wie Alkanoyloxy mit 1 bis 4 Kohlenstoffatomen, Tosyloxy, Mesyloxy und Triflat, Phosphonium, Sulfonium und Trialkylammonium, wie Trimethylammonium. Vorzugsweise ist Q Tosyloxy.



   Geeignete Beispiele von geschützten Carbonylgruppen   C = X    umfassen Ketale und Thioketale, wie beispielsweise, wenn X Diethoxy, Dimethylthio, Ethylendioxy, Propylendioxy oder Ethylendithio ist. Vorzugsweise ist X Ethylendioxy.  



   Die Reaktion wird in Abhängigkeit von der Reaktivität des verwendeten metallorganischen Reagens zweckmässig bei -20 C bis 100   C    in einer trockenen, inerten Atmosphäre unter Verwendung eines inerten Lösungsmittels, wie Tetrahydrofuran, Diethylether, Toluol oder Hexan, vorzugsweise Tetrahydrofuran, ausgeführt.



   Gemäss einer bevorzugten Ausführungsform der Erfindung entspricht das metallorganische Reagens der oben definierten Formel (III), und die Reaktion wird durch Lithiumhalogenide   undtoder    Kupfer(I)-halogenide katalysiert. Ein bevorzugter Katalysator ist Trilithiumtetratiodocuprat, das durch Mischen von Kupfer(I)-iodid und Lithiumiodid in einem Molverhältnis von 1:3 in Tetrahydrofuran hergestellt wird.



   Vorzugsweise ist   C = X    eine geschützte Carbonylgruppe.



  Die Reaktion zur Entfernung der Schutzgruppe kann in Abhängigkeit von der Natur der Gruppe C = X in jeder beliebigen zweckmässigen Weise ausgeführt werden. Wenn beispielsweise X Ethylendioxy ist, eignet sich die saure Hydrolyse. Die Entfernung der Schutzgruppe wird vorzugsweise ohne Isolierung des geschützten Nabumetones ausgeführt.



   Verbindungen der Formel (I) und (II) sind bekannte Verbindungen oder werden nach Methoden hergestellt, die denjenigen analog sind, die zur Herstellung strukturell ähnlicher bekannter Verbindungen angewandt werden.



   Das folgende Beispiel erläutert die Erfindung.



   Beispiel
EMI2.1     

Eine 0,2-molare Lösung von Trilithiumtetraiodocuprat wurde hergestellt, indem man 0,2 Mol Cuproiodid und 0,6 Mol Lithiumiodid in T.H.F.   Iöste    und mit T.H.F. auf 1,0 Liter auffüllte.



     3,3-Ethylendioxy-n-butoxy- l-p-toluolsulfonat    wurde nach der Methode von J.P. Yardley et al (J. Med. Chem. 10 (6), 1088-91, 1967) hergestellt mit der Ausnahme, dass das Lithiumaluminiumhydrid durch Natrium-bis-(2-methoxyethoxy)-aluminiumhydrid ersetzt wurde.



   Magnesium (1,1 g) wurde unter einer Stickstoffatmosphäre in den Reaktor gegeben, gefolgt von Tetrahydrofuran (20 ml). Das Magnesium wurde durch Zugabe von 1,2-Dibromethan (0,15 ml), das eine kleine Menge Iod enthielt, und Erhitzen zum gelinden Rückfluss aktiviert.



   Als die Iodfarbe verschwunden war, wurde im Verlauf einer Stunde eine Lösung von 2-Brom-6-methoxy-naphthalin (10,0 g) in T.H.F. (20 ml) zugesetzt, wobei der Rückfluss aufrechterhalten wurde.



   Die Lösung wurde auf -5   "C    abgekühlt. Eine 0,2-molare Lösung von Lithiumtetraiodocuprat in T.H.F. (2,5 ml) wurde zugesetzt, 10 Minuten später gefolgt von einer Lösung von   3,3-Ethylendioxy-n-butoxy- 1 -p-toluolsulfonat    (13,2 g) in T.H.F. (10 ml).



   Man liess die Temperatur des Reaktionsgemisches auf 20   C    steigen und erhöhte sie dann 2,5 bis 3,0 Stunden lang zum   Rückfluss.    Das Gemisch wurde auf ca. 5   "C    abgekühlt, und eine Lösung von Ammoniumchlorid (6 g) in Wasser (30 ml) wurde zugesetzt, gefolgt von konzentrierter Salzsäure(7 ml).



   Das Gemisch wurde mit Ethylacetat extrahiert und filtriert, und das Ethylacetat wurde im Vakuum entfernt. Der Rückstand wurde in Methylendichlorid (100 ml) gelöst, und die Lösung wurde mit Natriumbicarbonatlösung gewaschen und wieder eingedampft.



   Das rohe Produkt wurde in Isopropanol (33 ml) und Dimethylformamid (8 ml) gelöst, und die Lösung wurde auf 60   "C    erwärmt. Eine Lösung von Natriumpyrosulfit (4,4 g) in einem Gemisch aus Wasser (11 ml) und Isopropanol (2,2   ml)    wurde im Verlauf von ca. 0,5 Stunden zugesetzt, und man liess das Gemisch auf ca. 20   "C    abkühlen. Die Bisulfitverbindung wurde isoliert, mit Methanol (3 x 20 ml) und Aceton (2 x 20 ml) gewaschen und getrocknet und ergab 5,28 g Produkt.

 

   Die Bisulfitverbindung wurde in einem Gemisch von Wasser (20 ml) und Toluol (30 ml) suspendiert und mit   10%der    Natriumhydroxidlösung (15 ml) behandelt. Als die Zersetzung beendet war, wurde die Toluolschicht isoliert, über Magnesiumsulfat (4 g) filtriert und zur Trockene eingedampft. Die Umkristallisation aus industriellem vergälltem Alkohol (25 ml) ergab 4,0 g 4-(6-Methoxy-2-naphthyl)-butan-2-on. 



  
 



   DESCRIPTION



   This invention relates to a new process for the preparation of 4- (6-methoxy-2-naphthyl) butan-2-one.



   U.S. Patent 4,061,779 describes 4- (6-methoxy2-naphthyl) butan-2-one (nabumetone) and its use in the treatment of rheumatic and arthritic disorders. A number of methods of making the compound are also described. U.S. Patents 4,221,741 and 4,247,709 describe other processes for making nabumetones.



   Another process for the preparation of nabumetone has now been invented, which is characterized by an alkylation of 2-methoxynaphthalene in the 6-position.



   Accordingly, the present invention relates to a process for the preparation of 4- (6-methoxy-2-naphthyl) butan-2-one, which is characterized by the reaction of an organometallic reagent derived from a compound of the formula (I):
EMI1.6
 wherein Hal is halogen derived with a compound of formula (II):
EMI1.7
   where Q is a leaving group and C = X is an optionally protected carbonyl group, and then removing the protecting group from C = X if this represents a protected carbonyl group.



   Suitable meanings of Hal in formula (I) include iodine, bromine, chlorine and fluorine, preferably bromine.



   Suitable examples of organometallic reagents derived from a compound of formula (I) include Grignard reagents and organolithium compounds prepared by conventional methods. The organometallic reagent advantageously corresponds to the formula (III):
EMI 1.8

Q is a group that is easily replaced by nucleophiles. Examples of such groups include halogen such as chlorine, bromine and iodine, acyloxy such as alkanoyloxy having 1 to 4 carbon atoms, tosyloxy, mesyloxy and triflate, phosphonium, sulfonium and trialkylammonium such as trimethylammonium. Preferably Q is tosyloxy.



   Suitable examples of protected carbonyl groups C = X include ketals and thioketals, such as when X is diethoxy, dimethylthio, ethylenedioxy, propylenedioxy or ethylenedithio. Preferably X is ethylenedioxy.



   Depending on the reactivity of the organometallic reagent used, the reaction is expediently carried out at -20 ° C. to 100 ° C. in a dry, inert atmosphere using an inert solvent such as tetrahydrofuran, diethyl ether, toluene or hexane, preferably tetrahydrofuran.



   According to a preferred embodiment of the invention, the organometallic reagent corresponds to formula (III) defined above and the reaction is catalyzed by lithium halides and or copper (I) halides. A preferred catalyst is trilithium tetrate iodocuprate, which is prepared by mixing copper (I) iodide and lithium iodide in a molar ratio of 1: 3 in tetrahydrofuran.



   C = X is preferably a protected carbonyl group.



  The deprotection reaction can be carried out in any convenient manner depending on the nature of the C = X group. For example, if X is ethylenedioxy, acid hydrolysis is suitable. The protective group is preferably removed without isolating the protected nabumetone.



   Compounds of formula (I) and (II) are known compounds or are prepared by methods analogous to those used to prepare structurally similar known compounds.



   The following example illustrates the invention.



   example
EMI2.1

A 0.2 molar solution of trilithium tetraiodocuprate was prepared by mixing 0.2 mol cuproiodide and 0.6 mol lithium iodide in T.H.F. Iöste and with T.H.F. to 1.0 liter.



     3,3-ethylenedioxy-n-butoxy-l-p-toluenesulfonate was prepared by the method of J.P. Yardley et al (J. Med. Chem. 10 (6), 1088-91, 1967) with the exception that the lithium aluminum hydride was replaced by sodium bis (2-methoxyethoxy) aluminum hydride.



   Magnesium (1.1 g) was added to the reactor under a nitrogen atmosphere, followed by tetrahydrofuran (20 ml). The magnesium was activated by adding 1,2-dibromoethane (0.15 ml) containing a small amount of iodine and heating to gentle reflux.



   When the iodine color disappeared, a solution of 2-bromo-6-methoxy-naphthalene (10.0 g) in T.H.F. (20 ml) was added while maintaining reflux.



   The solution was cooled to -5 "C. A 0.2 molar solution of lithium tetraiodocuprate in THF (2.5 ml) was added, followed 10 minutes later by a solution of 3,3-ethylenedioxy-n-butoxy-1 - p-toluenesulfonate (13.2 g) in THF (10 ml).



   The temperature of the reaction mixture was allowed to rise to 20 ° C and then raised to reflux for 2.5 to 3.0 hours. The mixture was cooled to about 5 "C and a solution of ammonium chloride (6 g) in water (30 ml) was added, followed by concentrated hydrochloric acid (7 ml).



   The mixture was extracted with ethyl acetate and filtered, and the ethyl acetate was removed in vacuo. The residue was dissolved in methylene dichloride (100 ml) and the solution was washed with sodium bicarbonate solution and evaporated again.



   The crude product was dissolved in isopropanol (33 ml) and dimethylformamide (8 ml) and the solution was warmed to 60 ° C. A solution of sodium pyrosulfite (4.4 g) in a mixture of water (11 ml) and isopropanol ( 2.2 ml) was added over the course of about 0.5 hours, and the mixture was allowed to cool to about 20 ° C. The bisulfite compound was isolated, washed with methanol (3 x 20 ml) and acetone (2 x 20 ml) and dried to give 5.28 g of product.

 

   The bisulfite compound was suspended in a mixture of water (20 ml) and toluene (30 ml) and treated with 10% of the sodium hydroxide solution (15 ml). When the decomposition was complete, the toluene layer was isolated, filtered over magnesium sulfate (4 g) and evaporated to dryness. Recrystallization from industrial denatured alcohol (25 ml) gave 4.0 g of 4- (6-methoxy-2-naphthyl) butan-2-one.

Claims (10)

PATENTANSPRÜCHE 1. Verfahren zur Herstellung von 4-(6-Methoxy-2-naphthyl)-butan-2-on, gekennzeichnet durch die Umsetzung eines metallorganischen Reagens, das von einer Verbindung der Formel (I): EMI1.1 worin Hal Halogen ist, abgeleitet ist, mit einer Verbindung der Formel (II): EMI1.2 worin Q eine Abgangsgruppe ist und C = X eine gegebenenfalls geschützte Carbonylgruppe ist, und anschliessende Entfernung der Schutzgruppe von C=X, wenn dieses eine geschützte Carbonylgruppe darstellt.  PATENT CLAIMS 1. A process for the preparation of 4- (6-methoxy-2-naphthyl) -butan-2-one, characterized by the reaction of an organometallic reagent derived from a compound of the formula (I): EMI1.1  wherein Hal is halogen derived with a compound of formula (II): EMI1.2  wherein Q is a leaving group and C = X is an optionally protected carbonyl group, and then removing the protecting group from C = X if this represents a protected carbonyl group. 2. Verfahren nach Anspruch 1, dadurch gekennzeichnet, dass das metallorganische Reagens ein Grignardreagens oder eine lithiumorganische Verbindung ist.  2. The method according to claim 1, characterized in that the organometallic reagent is a Grignard reagent or an organolithium compound. 3. Verfahren nach Anspruch 2, dadurch gekennzeichnet, dass das metallorganische Reagens ein Grignardreagens der Formel (III): EMI1.3 ist.  3. The method according to claim 2, characterized in that the organometallic reagent is a Grignard reagent of the formula (III): EMI1.3  is. 4. Verfahren nach einem der Ansprüche 1 bis 3, dadurch gekennzeichnet, dass Q in Formel (II) Halogen, Alkanoyloxy mit 1 bis 4 Kohlenstoffatomen, Tosyloxy, Mesyloxy, Triflat, Phosphonium, Sulfonium oder Trialkylammonium bedeutet.  4. The method according to any one of claims 1 to 3, characterized in that Q in formula (II) is halogen, alkanoyloxy having 1 to 4 carbon atoms, tosyloxy, mesyloxy, triflate, phosphonium, sulfonium or trialkylammonium. 5. Verfahren nach einem der Ansprüche 1 bis 4, dadurch gekennzeichnet, dass X in Formel (II) Diethoxy, Dimethylthio, Ethylendioxy, Propylendioxy oder Ethylendithio bedeutet.  5. The method according to any one of claims 1 to 4, characterized in that X in formula (II) means diethoxy, dimethylthio, ethylenedioxy, propylenedioxy or ethylenedithio. 6. Verfahren nach einem der Ansprüche 1 bis 5, dadurch gekennzeichnet, dass man die Reaktion in einer trockenen, inerten Atmosphäre ausführt.  6. The method according to any one of claims 1 to 5, characterized in that one carries out the reaction in a dry, inert atmosphere. 7. Verfahren nach einem der Ansprüche 1 bis 6, dadurch gekennzeichnet, dass man die Reaktion in einem inerten organischen Lösungsmittel ausführt.  7. The method according to any one of claims 1 to 6, characterized in that one carries out the reaction in an inert organic solvent.   8. Verfahren nach einem der Ansprüche 1 bis 7, dadurch gekennzeichnet, dass man die Reaktion bei einer Temperatur von -20 "C bis 100 C ausführt.  8. The method according to any one of claims 1 to 7, characterized in that one carries out the reaction at a temperature of -20 "C to 100 C. 9. Verfahren nach einem der Ansprüche 1 bis 8, dadurch gekennzeichnet, dass man die Reaktion durch Lithiumhalogenide und/oder Kupfer(I)-halogenide katalysiert.  9. The method according to any one of claims 1 to 8, characterized in that the reaction is catalyzed by lithium halides and / or copper (I) halides. 10. Verfahren nach Anspruch 1, gekennzeichnet durch die Umsetzung eines metallorganischen Reagens der Formel (III): EMI1.4 mit einer Verbindung der Formel (II): EMI1.5 worin Q Tosyloxy bedeutet und C = X eine als Ethylenketal geschützte Carbonylgruppe bedeutet, wobei die Reaktion durch Trilithiumtetraiodocuprat katalysiert wird.  10. The method according to claim 1, characterized by the reaction of an organometallic reagent of the formula (III): EMI1.4  with a compound of formula (II): EMI1.5  where Q is tosyloxy and C = X is a carbonyl group protected as ethylene ketal, the reaction being catalyzed by trilithium tetraiodocuprate.
CH54087A 1986-02-15 1987-02-13 Prodn. of antiinflammatory 4-naphthyl-2-butanone deriv. CH670632A5 (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996040608A2 (en) * 1995-06-07 1996-12-19 Hoechst Celanese Corporation Use of 4-substituted 2-butanones to prepare nabumetone
EP0822174A1 (en) * 1996-07-29 1998-02-04 Archimica S.p.A. Process for the preparation of a naphthylbutanone

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5756851A (en) * 1996-10-21 1998-05-26 Albemarle Corporation Production of nabumetone or precursors thereof

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AT343104B (en) * 1975-01-08 1978-05-10 Beecham Group Ltd PROCESS FOR PRODUCING NEW NAPHTHALIN DERIVATIVES

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996040608A2 (en) * 1995-06-07 1996-12-19 Hoechst Celanese Corporation Use of 4-substituted 2-butanones to prepare nabumetone
WO1996040608A3 (en) * 1995-06-07 1997-01-30 Hoechst Celanese Corp Use of 4-substituted 2-butanones to prepare nabumetone
EP1223156A1 (en) * 1995-06-07 2002-07-17 Hoechst Celanese Corporation Use of 4-substituted 2-butanones to prepare nabumetone
EP0822174A1 (en) * 1996-07-29 1998-02-04 Archimica S.p.A. Process for the preparation of a naphthylbutanone
US5777170A (en) * 1996-07-29 1998-07-07 Archimica Spa Process for the preparation of a naphthylbutanone

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JPS62215546A (en) 1987-09-22
SE8700590D0 (en) 1987-02-13
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SE465924B (en) 1991-11-18
NL8700354A (en) 1987-09-01
DK75087A (en) 1987-08-16
DK75087D0 (en) 1987-02-13
GB8603768D0 (en) 1986-03-19
GR870254B (en) 1987-06-16
ES2004877A6 (en) 1989-02-16

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