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CH389608A - Process for the production of new ethers - Google Patents

Process for the production of new ethers

Info

Publication number
CH389608A
CH389608A CH880760A CH880760A CH389608A CH 389608 A CH389608 A CH 389608A CH 880760 A CH880760 A CH 880760A CH 880760 A CH880760 A CH 880760A CH 389608 A CH389608 A CH 389608A
Authority
CH
Switzerland
Prior art keywords
methyl
sep
general formula
ethyl
production
Prior art date
Application number
CH880760A
Other languages
German (de)
Inventor
Ernst Dr Jucker
Anton Dr Ebnoether
Original Assignee
Sandoz Ag
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 CH53760A external-priority patent/CH382164A/en
Application filed by Sandoz Ag filed Critical Sandoz Ag
Priority to CH880760A priority Critical patent/CH389608A/en
Priority to GB43068/60A priority patent/GB942152A/en
Priority to FR849932A priority patent/FR1279691A/en
Priority to BR125965/61A priority patent/BR6125965D0/en
Priority to ES0264077A priority patent/ES264077A1/en
Priority to DES72107A priority patent/DE1228262B/en
Priority to OA50776A priority patent/OA00698A/en
Publication of CH389608A publication Critical patent/CH389608A/en
Priority to CY37967A priority patent/CY379A/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
    • C07D211/22—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyrrole Compounds (AREA)

Description

       

  Verfahren zur     Herstellung    von neuen     Äthern       Es wurde gefunden, dass man zu neuen     Athern    der allgemeinen Formel 1,  
EMI0001.0004     
    worin     R1    ein Wasserstoff-,     Chlor-,    Brom- oder Fluor  atom oder die     Methyl-    oder die     Methoxygruppe    und       R.,    einen niederen     Alkylrest    bedeuten, gelangen kann,  indem man eine     Diphenylmethyl-Verbindung    der  allgemeinen Formel     1I     
EMI0001.0013     
    mit einer Verbindung der allgemeinen Formel     III,

       
EMI0001.0015     
    worin ein X die     Hydroxylgruppe,    das andere ein  Chlor- oder Bromatom bedeutet, umsetzt.    <I>Beispiel</I>       N-Methyl-2-[2'-(a-methyl-benzhydryloxy)-äthyl]-          pyrrolidin     Man versetzt die Suspension von 2,3 g pulveri  siertem     Natriumamid    in 30     cm3    Benzol mit 9,9 g       a-Methylbenzhydrol.    Anschliessend werden 7,4 g       N-Methyl-pyrrolidyl-(2)-äthylchlorid    zugesetzt und  die Lösung 20 Stunden am     Rückfluss    zum Sieden  erhitzt.

   Dann schüttelt man zuerst mit Wasser und  darauf     viermal    mit je 25     cm3    2n Salzsäure aus, stellt  die sauren Auszüge unter guter Kühlung mit Kali  lauge alkalisch und     nimmt    das ausgefallene Öl in  Äther auf. Nach Trocknen der ätherischen Lösung  über     Kaliumcarbonat    wird das Lösungsmittel einge  dampft und der Rückstand     im    Hochvakuum frak  tioniert destilliert, wobei das     N-Methyl-2-[2'-          (a-methyl-benzhydryloxy)-äthyl]-pyrrolidin    bei 143   unter einem Druck von 0,02 mm     Hg    übergeht.  



  n22     =   <B><I>1,5510.</I></B>  



  D Neutrales     Naphthalin-1,5-disulfonat:        Smp.    175  bis 176  aus Äthanol     (Zers.).     



  Analog wie oben beschrieben, werden aus       N-Methylpyrrolidyl-(2)-äthylchlorid    und einem     Di-          phenylcarbinol    der Formel     1I    die     Diastereoisomeren-          gemische    folgender Verbindungen erhalten:

      
EMI0002.0001     
  
    Substanz <SEP> Sdp./mm <SEP> Hg <SEP> Ausgangssubstanz
<tb>  Brechungsindex <SEP> (Formel <SEP> <B>11)</B>
<tb>  N-Methyl-2-[2'-(a-methyl-p-chlor-benz- <SEP> 154 /0,02 <SEP> Methyl-p-chlorphenyl  hydryloxy)-äthyl]-pyrrolidin <SEP> n <SEP> D <SEP> = <SEP> 1,5582 <SEP> phenylcarbinol
<tb>  N-Methyl-2-[2'-(a-methyl-p-brom-benz- <SEP> 162 0,02 <SEP> Methyl-p-bromphenyl  hydryloxy)-äthyl]-pyrrolidin <SEP> n <SEP> D <SEP> = <SEP> 1,5698 <SEP> phenylcarbinol
<tb>  N-Methyl-2-[2'-(a-methyl-p-methyl-benz- <SEP> 152 /0,02 <SEP> Methyl-p-tolyl  hydryloxy)-äthyl]-pyrrolidin <SEP> n <SEP> D <SEP> = <SEP> 1,5480 <SEP> phenylcarbinol



  Process for the production of new ethers It has been found that new ethers of the general formula 1,
EMI0001.0004
    where R1 is a hydrogen, chlorine, bromine or fluorine atom or the methyl or methoxy group and R., a lower alkyl radical, can be obtained by adding a diphenylmethyl compound of the general formula 1I
EMI0001.0013
    with a compound of the general formula III,

       
EMI0001.0015
    in which one X is the hydroxyl group and the other is a chlorine or bromine atom. <I> Example </I> N-methyl-2- [2 '- (a-methyl-benzhydryloxy) -ethyl] -pyrrolidine The suspension of 2.3 g of powdered sodium amide in 30 cm3 of benzene is mixed with 9.9 g of a-methylbenzhydrol. 7.4 g of N-methyl-pyrrolidyl- (2) -ethyl chloride are then added and the solution is refluxed for 20 hours.

   Then you shake out first with water and then four times with 25 cm3 of 2N hydrochloric acid each time, make the acidic extracts alkaline with potassium hydroxide while cooling them well and absorb the precipitated oil in ether. After drying the ethereal solution over potassium carbonate, the solvent is evaporated and the residue is fractionally distilled in a high vacuum, the N-methyl-2- [2'- (a-methyl-benzhydryloxy) -ethyl] -pyrrolidine at 143 under one pressure of 0.02 mm Hg.



  n22 = <B><I>1,5510.</I> </B>



  D Neutral naphthalene-1,5-disulfonate: m.p. 175 to 176 from ethanol (decomp.).



  Analogously as described above, the diastereoisomer mixtures of the following compounds are obtained from N-methylpyrrolidyl (2) ethyl chloride and a diphenylcarbinol of the formula 1I:

      
EMI0002.0001
  
    Substance <SEP> Sdp./mm <SEP> Hg <SEP> starting substance
<tb> Refractive index <SEP> (formula <SEP> <B> 11) </B>
<tb> N-methyl-2- [2 '- (a-methyl-p-chloro-benz- <SEP> 154 / 0.02 <SEP> methyl-p-chlorophenyl hydryloxy) -ethyl] -pyrrolidine <SEP> n <SEP> D <SEP> = <SEP> 1.5582 <SEP> phenylcarbinol
<tb> N-methyl-2- [2 '- (a-methyl-p-bromo-benz- <SEP> 162 0.02 <SEP> methyl-p-bromophenyl hydryloxy) -ethyl] -pyrrolidine <SEP> n <SEP> D <SEP> = <SEP> 1.5698 <SEP> phenylcarbinol
<tb> N-methyl-2- [2 '- (a-methyl-p-methyl-benz- <SEP> 152 / 0.02 <SEP> methyl-p-tolylhydryloxy) -ethyl] -pyrrolidine <SEP> n <SEP> D <SEP> = <SEP> 1.5480 <SEP> phenylcarbinol

Claims (1)

PATENTANSPRUCH Verfahren zur Herstellung von neuen Äthern der allgemeinen Formel 1, EMI0002.0004 worin R1 Wasserstoff-, Chlor-, Brom- oder Fluor atom oder die Methyl- oder die Methoxygruppe und R2 einen niederen Alkylrest bedeuten, dadurch ge kennzeichnet, PATENT CLAIM Process for the production of new ethers of the general formula 1, EMI0002.0004 where R1 is a hydrogen, chlorine, bromine or fluorine atom or the methyl or methoxy group and R2 is a lower alkyl radical, characterized in that dass man eine Diphenylmethyl-Verbin- dung der allgemeinen Formel II Ra C II -/ X mit einer Verbindung der allgemeinen Formel III, /CHZ CH, X-CHr-CHF HC\ \ III N CH2 1 C H3 worin ein X die Hydroxylgruppe, das andere ein Chlor- oder Bromatom bedeutet, umsetzt. that a diphenylmethyl compound of the general formula II Ra C II - / X with a compound of the general formula III, / CHZ CH, X-CHr-CHF HC \ \ III N CH2 1 C H3 in which one X is the hydroxyl group, the other means a chlorine or bromine atom. UNTERANSPRUCH Verfahren nach Patentanspruch, zur Herstellung von N-Methyl-2-[2'-(a-methyl-p-chlor-benzhydryloxy- äthyl] - pyrrolidin, dadurch gekennzeichnet, dass man N-Methyl-pyrrolidyl-(2)-äthylchlorid mit Methyl- p-chlor-phenyl-phenylcarbinol umsetzt. SUBCLAIM Process according to claim for the preparation of N-methyl-2- [2 '- (a-methyl-p-chlorobenzhydryloxy-ethyl] -pyrrolidine, characterized in that N-methyl-pyrrolidyl- (2) ethyl chloride with methyl-p-chloro-phenyl-phenylcarbinol.
CH880760A 1960-01-19 1960-08-03 Process for the production of new ethers CH389608A (en)

Priority Applications (8)

Application Number Priority Date Filing Date Title
CH880760A CH389608A (en) 1960-01-19 1960-08-03 Process for the production of new ethers
GB43068/60A GB942152A (en) 1960-01-19 1960-12-14 Improvements in or relating to benzhydryl ethers
FR849932A FR1279691A (en) 1960-01-19 1961-01-17 New benzhydryl ethers and their preparation
BR125965/61A BR6125965D0 (en) 1960-01-19 1961-01-18 PROCESS FOR THE PREPARATION OF NEW ESTERS
ES0264077A ES264077A1 (en) 1960-01-19 1961-01-18 Improvements in or relating to benzhydryl ethers
DES72107A DE1228262B (en) 1960-01-19 1961-01-18 Process for the production of new pyrrolidine derivatives and their salts
OA50776A OA00698A (en) 1960-01-19 1964-12-08 New benzhydryl ethers and their preparation.
CY37967A CY379A (en) 1960-01-19 1967-03-04 Improvements in or relating to benzhydryl ethers

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CH53760A CH382164A (en) 1960-01-19 1960-01-19 Process for the production of new ethers
CH880760A CH389608A (en) 1960-01-19 1960-08-03 Process for the production of new ethers
CH1089760 1960-09-27

Publications (1)

Publication Number Publication Date
CH389608A true CH389608A (en) 1965-03-31

Family

ID=27172192

Family Applications (1)

Application Number Title Priority Date Filing Date
CH880760A CH389608A (en) 1960-01-19 1960-08-03 Process for the production of new ethers

Country Status (8)

Country Link
BR (1) BR6125965D0 (en)
CH (1) CH389608A (en)
CY (1) CY379A (en)
DE (1) DE1228262B (en)
ES (1) ES264077A1 (en)
FR (1) FR1279691A (en)
GB (1) GB942152A (en)
OA (1) OA00698A (en)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1307255A (en) * 1970-09-12 1973-02-14 Pfizer Ltd Substituted basic benzhydryl ethers
JPS5223068A (en) * 1975-08-13 1977-02-21 Nippon Kayaku Co Ltd Preparation of optically active 1-methyl -2-(2'-(alpha-methyl-p-chlorobenz hydryloxy) ethtyl) pyrrolidine fumarates
US4835164A (en) * 1987-02-20 1989-05-30 A. H. Robins Company, Incorporated Aryloxymethyl derivatives of nitrogenous heterocyclic methanols and ethers thereof
WO2004064845A1 (en) 2003-01-14 2004-08-05 Gilead Sciences, Inc. Compositions and methods for combination antiviral therapy
TWI375560B (en) 2005-06-13 2012-11-01 Gilead Sciences Inc Composition comprising dry granulated emtricitabine and tenofovir df and method for making the same
TWI471145B (en) 2005-06-13 2015-02-01 Bristol Myers Squibb & Gilead Sciences Llc Unitary pharmaceutical dosage form
CN107011228B (en) * 2017-05-24 2019-08-09 浙江诚意药业股份有限公司 A kind of preparation method of clemastine fumarate

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE934890C (en) * 1951-10-07 1955-11-10 Chem Fab Promonta Ges Mit Besc Process for the preparation of basic benzhydryl ethers

Also Published As

Publication number Publication date
DE1228262B (en) 1966-11-10
OA00698A (en) 1967-07-15
BR6125965D0 (en) 1973-06-28
ES264077A1 (en) 1961-07-16
FR1279691A (en) 1961-12-22
GB942152A (en) 1963-11-20
CY379A (en) 1967-03-04

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