BE739305A - 3 pyridylemthanol p-chlorophenoxyisobutyrate com- - bining vasodilatory and anti-lipaemic activity - Google Patents

3 pyridylemthanol p-chlorophenoxyisobutyrate com- - bining vasodilatory and anti-lipaemic activity

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Publication number
BE739305A
BE739305A BE739305DA BE739305A BE 739305 A BE739305 A BE 739305A BE 739305D A BE739305D A BE 739305DA BE 739305 A BE739305 A BE 739305A
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acids
acid
chloride
pyridylmethanol
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D213/00Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/28Radicals substituted by singly-bound oxygen or sulphur atoms
    • C07D213/30Oxygen atoms

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pyridine Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

3-Pyridylemthanol p-chlorophenoxyisobutyrate combining vasodilatory and anti-lipaemic activity. M3A. Is a new compound of formula (I):- prepared by (a) reacting p-chlorophenoxy isobutyryl chloride and 3-pyridylmethanol (II) opt. in the presence of a solvent and opt. together with an acid-binder; or (b) reacting p-chlorophenoxyisobutyric acid with (II) in the presence of a catalyst e.g. toluene-p-SO3H.

Description

  

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  ..C'DC4d' pour 1.obtont1on de 44riv4a des &c1dtua aryloxy- 1.obUtyrlJI 
 EMI1.2 
 La pt"*nte invention * pour,objet un goeMé pot l'cbtMtiot de d6das des scidaes s.sIsatyr3ts. 



  &M 4tude< salsxs r6cmt*  ont dacotr4 queune *4rie d'*cidM arIoqr3.cbtyt3q et IUM thijs Montrât MM acavité accontu4d dans la réduction de lipide et du ctcl t4rol dari* le smog et la foie, "11 ant 14 tablM <tbiMWC4roti<p ;rr3oclqt). 



  Par aîlleurs, on sait que la propri" pr4sMt&t par 

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 certaine dérivé* de la pyridine est   d'agir   comme protecteurs 
 EMI2.1 
 vasculaires dans les affections cardiaquex ot cÓr 4>ra1e.. 



   Il est fréquent do voir associas les deux facteurs pathologiques,   principalement   dans la sénilité, raison pour laquelle on a cherché à créer une nouvelle molécule active 
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 qui agitato simultanément fuce aux hyprcholgatérolém10. et eux hyporllpémioa ot dans les cadras atliroscli6cotiques que callea-ci occasionnent* Las résultats pharmacoloqiques et cliniques ont dé- mmù6 que lorsque 3'on combine dans une mama molscu3.a los s,rposata v..odl1atateUt's et antil1p'm1ques, on obtient des rultats qui "611or.,nt de façon marqu6" l'état subjectif et objectif du patient. 



   Cotte invention a pour objet la préparation d'un nou- 
 EMI2.3 
 veau co<apoee chir4îquo et, en particulier, d*un nouveau con- posé pouvant âtre inclus dans la série des esters 4es acides ph4noxy1aosutyri-<ues avec des alcools de la série des pyridi-   nalcanols.   de   Maniera   plus concrète, elle a pour objet l'obten-   tion   d'un ester dans lequel la partie acide est formée d'un 
 EMI2.4 
 ac.1dtt pb&noxy1sobutyr1quQ porteur d'un substituant: dans le noyau benzénique et l'alcool est formé d'un noyau pyridine- que avoeu JM substitsant alcoyiique porteur de la fonction alcool.

   Los formules générales dont on dérive l'ester man- tionn4 peuvent atre repre*anté<M par la structure suivante: 
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 e-:.,3moa c My CCH2)n OH 
 EMI2.6 
 Dans sos aspocts plus 11ra1Us. la présente inventico 1JJa1te les substituanu dans la fragmmt acide' la pos1UoA 

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   para   et dans le   fraient     alcool 11   la position 3 de la pyri- dine. 



     -en   concrétisant dans la sens de fixer la type et la grandeur des substituants dans les deux fragments de la molé- cule de l'ester, objet de la présente invention, on peut dire que parmi les substituants en position para, situés dans la noyau benzénique de la partie acide, celui qui est préféré   parmi le   groupe formé par les   halognes,   est le chlore. Par   ailleurs,   pariai les diverses chaînes   alcoyliques   de grandeur différente qui peuvent être unies à l'atome 3 de la molécule de pyridine, on préfère celle qui possède un groupe méthylé- nique   unique.   L'objet fondamental de la présente invention est que la fonction alcoolique se trouve dans la chaîne la- térale du noyau pyridinique. 



   Les formules de l'acide et de l'alcool formant l'es-   ter objet de l'invention sont ;   
 EMI3.1 
 CH3 ci Éoox Ho-c; CH3 - N 
11 a été   démontré   que pour la préparation de l'ester, objet de la présente invention,   concrètement,le     p-chlorophé-   noxyisobutyrate de   3-pyridylméthanol   dont la formule est :

   
 EMI3.2 
 CH3 ci-o- t-- 1 -CC>OC% 3 0 L3   On   peut utiliser les méthodes de préparation normales pour la synthèse de ce genre de dérivés, mais on a pu cons- tater, et   &   cet effet   s'est   avéré utile, le procédé qui consiste à   mettre   en contact, en présence d'un solvant  le 

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 chlorura de l'acide p-chlo:->gìinoxyi=zJb#lzwi z;i ¯>i =. <.= dylméthanol déjà en présento non d ?m=e x;c'=;m-J-. : :I. 
 EMI4.2 
 d'acide chlorhydrique. 
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  En étudiant le procéda de préparation -c3z pt#ti<i,ii, objet de la présente inventiez, on a obsarvê qu-- lee x,5N-- vants les plus adéquats puir %tre utilisée <scco i=fl?.F,<x-; :éé±= tionnel ont été des soivsats ràor. palairùi aë 2.'.: le benzène, l 'é1:he:rét."1yl.r::u(; etc. Ba ce <!w.i. scc. substance captrice d'acide c:::hlorhydri:ç:Q j en ::;:.,X:"; ,j;J; :::.::: liz lisation, ntus avons const#1.E lMti':.e dej 2ma=1,-> izri- :1<gi.-i capables de se combiner aves 2. àacide chlc:::):'!'.:2l7L-:.,:.:> '-':.1 : gage de la réaction, telles ifc-s subs2ncGZ 'u jri# da la pyridine, des q,ai;olôk=es, et il <3."; :l:'.ra3.st dG signaler que l'on peut ;.tilisex 20e 3-pyridHc:ê&-!3l, iHi- comme substance captric toeJt e=1 ayant soi i;3 ca cas d'utiliser un excédent de c..:; réactif pùr .s's.pst <S# qu-1 a été calculé pour la pr3paratîon de l'ester.

   CR a <à#staté que les produits obtenus par <3 p,-oci5dé de préparation de l'ester sont différents suivant que la prçf-1,aratio.-I ;n.:mtion- née a lieu ou non en présence d'un capteur d'acide ehlorhy# drique,dans le prentier cas (en présence d'un capi;@..1r), on 
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 obtient l'ester basique et dans le deuxième cas (absence d'un capteur), le chlorhydrate de celui-ci. 
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  Un autre procédé qui s'est avéré utîle- pour la prépa- 
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 ration de l'ester, objet de la présente invention, a été de 
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 procéder à la condensation du chlorure de l'acide p-chlcro- phénoxyisobutyrique ave le 3-pyridy1reth.cl, r7'e pour mole et en l'absence de solvant, en oaintena."1t la aêlana 3: une température de 120-130'C pendant une paricd-s <!.2 2-3 heusES, 

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 .:..L ;:'odu1't v °¯.< d26'ittr '< ' 'a d ¯ ¯ , "l:0c&4& ext 1. d11o...."'1ty- e de I''<estsc< 33 faisant réaùir 1 fVt'::e ..v,J.sQ.tt'r3.qt! -;.c yu, li,v:3 de 3-'xiylnnl 1:d.t on fjâ3#1C' do ca- t;:11yseurs .;:.;.:. s*"<t sàia 0UX, 'C; a: ::: <=Jatater la forntion de .: t.r .m :.ra.:.:: se cr.1:;. :! ::-.. : -;:.;: àtre un proc4d' en- ""1s,,),,,r pour 14 yr4pérz<ion -.¯,s :.:< "::. '': -;: clté. i.:::

   1.z 5=hl.-- ..., . :::i':oUi'=4\t. do 3-p:rl- 2r.êth&nl .50 """''''''.-+- il"""'" .,- .' 8"""a halle A"''''se qui ....4i""t"'''11''',, "\ zal 1,.-ùm ci <z=1. ,.2....-" 3. 52-53 C, ..f t'': 3's?' 1#blo ans. 1?e==s, 1-s ?.1:>1, 1>,5i:#> -:.::- 5b .,;::t le toluène. 



  2t 9fi..."¯?, :..1', !ë5 :::i"'-:t-:; e..:;:-.;.::.::":"4 ..u:a..t5 ecE-'-B r3p.'s'.."5'.-a...* le α.±21 Xl*, ±sf.za La 7't-;r:!:::..; à*.li.#'1? i=a ..;. d.3 155-1S?'C sous Q, 3 r'llt d . E: 'A, .m.Jis 5>.i3 ;''; ..p; -,¯:::.';';-.1. ,;':.: ,. '. i'û..s ( de l'ester, objet de la pE?'..;-.- :''.ti--*., T. -3tse enduite en fusant passer 1.1."1 .c1:-:I:''!::t d t ::,;:.; d:"":::;Y.2'::;.':::::2 à travers une solutlm écisae da pr.:).:it. .w m: -=3 fcr est recrista11sé da.-u; du r- ,1 Llcc.'Vl -;;tjr'2.;.-;: tertiaire>, on obtient des y3.> qui foné>nt À 132-14.C. Le sél de l'ester dè la. prés.:ni::e . : : io:x est in!!ol1ilile d2.s le xylène, le tolcène, 1*éthcr de ptroe; il est peu sclubio à. froid dans l'acéto- nyt:.rl1c, ?e .-:z:. et le x#s-:.fl.ß il est s3ablp.- seat soluble à rh<u±1 ::#1;s les trois ':!2r:;Ír.ars solvants.

   Le produît .3i.''.3y.i ...s..5: ïS. 4:,rk...a...r.'..Gw.. 2re. 



  Afin dû J.1r la cpr1?ion de la. .wu'ii4L in- " t,. i.". d3 : a< ...'' ' m .a: 30nt clvrit57 ss qua cela signifie #ne J..iit3.ti:;:1 çi >1=##que è.'.:.s la, :; '%' #.a.i'-C..i3 de c'a nouveau .rL.wiF   t .$:.:::a':-,F'â do l'ester 1"v::..â.â.i. 

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 txeaol. 1 On affltiomw une solution det 23,3 9 de chlorure 4. cidt p.ch10r0ph4noxy1.8Obuq.rlque du boenMne (100 al) à une solution de 21 g de 3-pyr1dylslithanol dans 200 ml do ben- zèm anhydre, goutte 1 goutte et en refroidissant:. en mainte- nant la tenpérature 1 environ SOC* On agite vigoufeuseoMmt et abandonne le tout une fois l'addition taiab# à la tempéra- ture ordinaire pendant 24 heures. Cs filtre la précipité et 3.'JE lave ,YftTC du 'I#:Ft'r. Lo filtrat esb Lors o1s f01s à l'eau froide e4; :Jt!ch'; sur du auiiate de gi'!c"'1  t"n évapora le solvant et rectifia l'imilo 1u11o.

   L= fraction qui passe cntro 170-1SC*C sous 1 de prssic* est séparée et re=tlfiéee Point d'u3. rs:a 155-1S?*C, U3 0,3 r.-.. La pré- parat10n du .crS;. ta do l'ester prépar6 $alon l'exemple z. est réalis6e on i4iw,..E4 passas un courant d'acide chlorhydri- que à travers, une Mluticn .->.;>' de l'ester basique. Il ie fercM un z"'.L-ai.,J.4ar. de ,,;:;;::1st:au.'IC \1.t .r::::-:..i1't)::'li.!:é3 4a du :T3'$1.*'C3. .": i ± ment cl l12-à33*c. 



  Z,x---n2le. 



  .....1 !>MoiII l1li. 



  13 ';Q::1pt1rt;n.re ::r1i:'Jirl±!. e:- .2'cH .:Jb(;:n'le oluiC!1 A la <.o'3psrt:!re crdi:!ôire rr "i .3'ddiicR'''ie a solutic de 11,6 9 d# :r. :.-: dt....:.:j,>:b -;lo.':"Fn:;o::::::-iso1;:,u.::iqu:! dans 50 nl de bnsn à .m>3 soluticn de sus 0; de -ïâr3.v.- ,^i tt3,TIt7 danu GO ni de t:.'.1:."l',?w Le tout e.3& agite : e2'gf::i:,z ,a.'l.éa t3ent pendtMit l'addition du chlorure d'acide. on chauffa au reflux le tout !-,.:n.j.mt 3-4 heures. Le pr.4<ip,iÉ4 du chlorhydra- te de l'aster est filtre on le lave deux fois avec du ben- x-éne anhydre puis en le .keha.. Cn tailla a da-5 dru :anol nert.,aire. Point <Se fusion 133-134.C. 

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  Bxeaple 3 .. - ¯ - On ajoute lentement 2,33 g de chlorure d'acide p- chlorophénoxyisobutyriqçoe à 1,1 g de 3-pyridylméthanol en refroidissant. On chauffe le tout pendant 30-40 minutes à une température voisine do 140 C.   On   refroidit le résidu, le lave avec du benzène et recristallise le produit. La chlor- hydrate de l'ester fond à 130-132 C. 



  Exemple 4 
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 On met en suspension 40 q d'acide ph3arerphnaxy3so- butyrique dans :C43 ml de 3.-pYr'ity?thà x3. en présence de 2 g d'acide p-toI.r:e-sn3.foniqz:e. On chauffe le tout à 110*C et on sépare   l'eau     àrmée   lors de la réaction. Après avoir re-   cueilli   approximetivement quelque 3 g d'eau, on cesse de chauffer et on refroidit le tout. On lave avec de   l'eau   la masse résultant de la réaction, on extrait avec du benzéne, 
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 on 5èéh. distille et rèctifi pai:r ol:t<nir un produit qui bouz à 150-155*c scs Of3m de pression. 

**ATTENTION** fin du champ DESC peut contenir debut de CLMS **.



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  ..C'DC4d 'for 1.obtont1on de 44riv4a des & c1dtua aryloxy- 1.obUtyrlJI
 EMI1.2
 The pt "* nte invention * for, object a goeMé pot the cbtMtiot of d6das of the s.sIsatyr3ts scidae.



  & M 4tude <salsxs r6cmt * have dacotr4 queue * 4rie d '* cidM arIoqr3.cbtyt3q and IUM thijs showed MM acavity increased in reduction of lipid and ctcl t4rol dari * smog and liver, "11 ant 14 tabl4Mrot <tbiMW p; rr3oclqt).



  By further, we know that the property "pr4sMt & t

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 certain derivative * of pyridine is to act as protectors
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 vascular disease in cardiac affectionsx ot cÓr 4> ra1e ..



   It is common to see the two pathological factors associated, mainly in senility, which is why we tried to create a new active molecule.
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 which simultaneously agitated the hyprcholgaterolem10. and they hyporllpémioa ot in the atliroscli6cotic cadras that callea this cause * The pharmacological and clinical results have been shown that when we combine in one molscu3.a los s, rposata v..odl1atateUt's and antil1pques, we obtain results which "611or., markedly" the subjective and objective state of the patient.



   This invention relates to the preparation of a new
 EMI2.3
 calf co <apoee chir4îquo and, in particular, with a new compound which can be included in the series of esters of ph4noxy1aosutyri- ues acids with alcohols of the series of pyridinalcanols. de Maniera more concrete, its object is to obtain an ester in which the acid part is formed of a
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 ac.1dtt pb & noxy1sobutyr1quQ carrying a substituent: in the benzene ring and the alcohol is formed of a pyridine ring that has JM alkyl substituent carrying the alcohol function.

   The general formulas from which the man- tion4 ester is derived can be denoted * before <M by the following structure:
 EMI2.5
 e -:., 3moa c My CCH2) n OH
 EMI2.6
 In sos aspocts plus 11ra1Us. the present inventico 1JJa1te the substitutes in the acidic fragmmt 'the pos1UoA

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   para and in spawn alcohol 11 the 3-position of pyridine.



     - by concretizing in the sense of fixing the type and size of the substituents in the two fragments of the ester molecule, object of the present invention, it can be said that among the substituents in the para position, located in the nucleus benzene of the acidic part, which is preferred among the group formed by halogens, is chlorine. On the other hand, of the various alkyl chains of different size which can be joined to atom 3 of the pyridine molecule, the one which has a single methylene group is preferred. The fundamental object of the present invention is that the alcoholic function is found in the side chain of the pyridine ring.



   The formulas of the acid and of the alcohol forming the object of the invention are;
 EMI3.1
 CH3 ci Eoox Ho-c; CH3 - N
It has been demonstrated that for the preparation of the ester, object of the present invention, specifically, 3-pyridylmethanol p-chlorophenoxyisobutyrate, the formula of which is:

   
 EMI3.2
 CH3 ci-o- t-- 1 -CC> OC% 3 0 L3 The normal preparation methods can be used for the synthesis of this kind of derivative, but it has been possible to observe, and this effect has been shown useful, the process which consists in contacting, in the presence of a solvent, the

 <Desc / Clms Page number 4>

 
 EMI4.1
 p-chlo acid chlorura: -> gìinoxyi = zJb # lzwi z; i ¯> i =. <. = dylmethanol already in presento not d? m = e x; c '=; m-J-. :: I.
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 hydrochloric acid.
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  By studying the preparation procedure -c3z pt # ti <i, ii, object of the present invention, we observed that the most adequate lee x, 5N-- could be used <scco i = fl? .F , <x-; : éé ± = tionnel have been soivsats ràor. palairùi aë 2. '.: benzene, é1: he: ret. "1yl.r :: u (; etc. Ba ce <! wi scc. acid scavenging substance c ::: hlorhydri: ç: Q j in ::;:., X: ";, j; J; :::. ::: liz lization, we have const # 1.E lMti ':. e dej 2ma = 1, -> izri-: 1 <gi.-i capable of combining with 2.acid chlc :: :): '!' .: 2l7L -:.,:.:> '-' :. 1: pledge of the reaction, such ifc-s subs2ncGZ 'u jri # da pyridine, q, ai; olôk = es, and it <3. ";: l:'. ra3.st dG point out that we can; .tilisex 20e 3-pyridHc: ê & -! 3l, iHi- like substance captric toeJt e = 1 having itself i; 3 ca case of using an excess of c ..:; reagent pùr .s's.pst <S # qu-1 was calculated for the preparation of the ester.

   CR a <to # stated that the products obtained by <3 p, -oci5dé of preparation of the ester are different depending on whether the prçf-1, aratio.-I; n.: Reaction takes place or not in the presence of 'an ehlorhy # dric acid scavenger, in this case (in the presence of a capi; @ .. 1r), we
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 obtains the basic ester and in the second case (absence of a sensor), the hydrochloride thereof.
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  Another process which has proved useful for the preparation
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 ration of the ester, object of the present invention, was
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 condense the chloride of p-chlcro-phenoxyisobutyric acid with 3-pyridy1reth.cl, r7'e for mole and in the absence of solvent, in oaintena. "1t la aêlana 3: a temperature of 120- 130'C during a paricd-s <!. 2 2-3 hours,

 <Desc / Clms Page number 5>

 
 EMI5.1
 .: .. L;: 'odu1't v ° ¯. <D26'ittr' <'' ad ¯ ¯, "l: 0c & 4 & ext 1. d11o ...." '1ty- e of I' '<estsc <33 making 1 fVt ':: e ..v, J.sQ.tt'r3.qt! - ;. c yu, li, v: 3 of 3-'xiylnnl 1: d.t on fjâ3 # 1C 'do c- t;: 11yseurs.;:.;.:. s * "<t sàia 0UX, 'C; a: ::: <= Date the forntion of.: tr .m: .ra.:. :: se cr.1:;.:! :: - ..: -;:.;: to be a proc4d 'en- "" 1s ,,) ,,, r for 14 yr4pérz <ion -.¯, s:.: <"::. '': - ;: key. i. :::

   1.z 5 = hl .-- ...,. ::: i ': oUi' = 4 \ t. do 3-p: rl- 2r.êth & nl .50 "" "'' '' '' .- + - il" "" '"., -.' 8 "" "a hall A" '' '' which .... 4i "" t "'' '11' '' ,," \ zal 1, .- ùm ci <z = 1., .2. ...- "3. 52-53 C, ..f t '': 3's? ' 1 # blo years. 1? E == s, 1-s? .1:> 1, 1>, 5i: #> -:. :: - 5b.,; :: t toluene.



  2t 9fi ... "¯ ?,: .. 1 ',! Ë5 ::: i"' -: t- :; e ..:;: -.;. ::. :: ":" 4 ..u: a..t5 ecE -'- B r3p.'s '.. "5' .- a ... * on Î ±. ± 21 Xl *, ± sf.za La 7't-; r:! ::: ..; à * .li. # '1? I = a ..;. D.3 155-1S? 'C under Q, 3 r'llt d. E:' A, .m.Jis 5> .i3; ''; ..p; -, ¯ :::. ';'; -. 1.,; ' :.:,. '. i'û..s (of the ester, object of the pE?' ..; -.-: ''. ti - *., T. -3tse coated by fusing pass 1.1 . "1 .c1: -: I: ''! :: tdt ::,;:.; D:" ":::; Y.2 '::;.' ::::: 2 through a solutlm ecisae da pr.:).:it. .w m: - = 3 fcr is recrystalised da.-u; of r-, 1 Llcc.'Vl - ;; tjr'2.; .- ;: tertiary>, we obtain y3.> which melts> nt At 132-14.C. The ester sel from there. pres .: ni :: e. :: io: x is in olilil, xylene, tolcene, petroleum ethers; it is little sclubio to. cold in aceto- nyt: .rl1c,? e .-: z :. and the x # s - :. fl.ß it is s3ablp.- seat soluble at rh <u ± 1 :: # 1; s all three ':! 2r:; Ír.ars solvents.

   The product .3i. ''. 3y.i ... s..5: ïS. 4:, rk ... a ... r. '.. Gw .. 2nd.



  In order to J.1r the cpr1? Ion of the. .wu'ii4L int "t ,. i.". d3: a <... '' 'm .a: 30nt clvrit57 ss qua that means #ne J..iit3.ti:;: 1 çi> 1 = ## que è.'.:. s la,:; '%' # .a.i'-C..i3 de c'a new .rL.wiF t. $:. ::: a ': -, F'â do ester 1 "v :: .. â.â.i.

 <Desc / Clms Page number 6>

 
 EMI6.1
 txeaol. 1 We affltiomw a solution of 23.3 9 chloride 4.cidt p.ch10r0ph4noxy1.8Obuq.rlque of boenMne (100 al) to a solution of 21 g of 3-pyr1dylslithanol in 200 ml of anhydrous benzene, drop 1 drop and by cooling :. while maintaining the temperature 1 approximately SOC * The mixture is stirred vigorously and the whole is left after the addition taiab # at room temperature for 24 hours. Cs filters the precipitate and 3.'JE washes, YftTC from 'I #: Ft'r. Lo filtrate esb When o1s f01s in cold water e4; : Jt! Ch '; The solvent evaporated and the imilo 1u11o ground.

   L = fraction which passes cntro 170-1SC * C under 1 of prssic * is separated and re = tlfiée Point of u3. rs: a 155-1S? * C, U3 0.3 r.- .. The preparation of .crS ;. ta do the ester prepared $ alon example z. A stream of hydrochloric acid is passed through a stream of hydrochloric acid through a Mluticn .->.;> 'of the basic ester. It ie fercM un z "'. L-ai., J.4ar. De ,,;: ;; :: 1st: au.'IC \ 1.t .r :::: -: .. i1't) :: 'li.!: é3 4a du: T3' $ 1. * 'C3. ": i ± ment cl l12-à33 * c.



  Z, x --- n2le.



  ..... 1!> MoiII l1li.



  13 '; Q :: 1pt1rt; n.re :: r1i:' Jirl ± !. e: - .2'cH.: Jb (;: n'le oluiC! 1 A la <.o'3psrt:! re crdi:! ôire rr "i .3'ddiicR '' 'ie a solutic of 11.6 9 d #: r.: .-: dt ....:.: J,>: b -; lo. ': "Fn:; o :::::: - iso1;:, u.::iqu: ! in 50 nl from bnsn to .m> 3 soluticn from sus 0; from -ïâr3.v.-, ^ i tt3, TIt7 danu GO ni from t:. '. 1:. "l',? w The whole e .3 & stir: e2'gf :: i:, z, a.'l.éa t3ent while the addition of the acid chloride. The whole was heated to reflux! - ,.: njmt 3-4 hours. pr.4 <ip, iE4 of the aster hydrochloride is filtered, washed twice with anhydrous benzene then in .keha .. Cn cut a da-5 dru: anol nert., ary .Melting point 133-134. C.

 <Desc / Clms Page number 7>

 
 EMI7.1
 



  Bxeaple 3 .. - ¯ - 2.33 g of p-chlorophenoxyisobutyric acid chloride are slowly added to 1.1 g of 3-pyridylmethanol while cooling. The whole is heated for 30-40 minutes at a temperature in the region of 140 ° C. The residue is cooled, washed with benzene and the product recrystallized. The ester hydrochloride melts at 130-132 ° C.



  Example 4
 EMI7.2
 40g of ph3arerphnaxy3so-butyric acid is suspended in: C43 ml of 3.-pYr'ity ™ th at x3. in the presence of 2 g of p-toI.r acid: e-sn3.foniqz: e. The whole is heated to 110 ° C and the water separated off during the reaction. After having collected approximately 3 g of water, the heating is stopped and everything is cooled. The mass resulting from the reaction is washed with water, extracted with benzene,
 EMI7.3
 we 5èéh. distill and rectify: r ol: t <nir a product which boils at 150-155 * c scs Of3m of pressure.

** ATTENTION ** end of DESC field can contain start of CLMS **.

 

Claims (1)

REVENDICATIONS 1. Procdé pour l'obtention de dérivas des acides aryloxyisobutyriqucs, de fornule : EMI7.4 ²H3 Cl 0, -CCOOCH2 0 (1) - 1 \-NI CH3 caractérisé en ce que l'on fait réagir du chlorure diacide EMI7.5 p-chlorophZ-noxyisobuty--7iqua avec du 3-pyridylméthanol e."1 présence d'une substance captrice d'acide chlorhydrique. <Desc/Clms Page number 8> EMI8.1 CLAIMS 1. Process for obtaining derivatives of aryloxyisobutyric acids, of the formula: EMI7.4 ²H3 Cl 0, -CCOOCH2 0 (1) - 1 \ -NI CH3 characterized in that diacid chloride is reacted EMI7.5 p-chlorophZ-noxyisobuty - 7iqua with 3-pyridylmethanol e. "1 presence of a hydrochloric acid scavenger. <Desc / Clms Page number 8> EMI8.1 2. Procède pour 1.obt<:ntion de dériv-Js des acides arylcxylaobutyrlquos, sden la revendication Il caractérisa en ce que l'on fait rl**ajîr du chlorure d'acte p-chloophé- noxylsobutytîque avec du 3-pyridylméthanol en présence d'un solvant sans la préscnco do substances captricca d'acide chlorhydrique, de sorte que ce dem1<.!r intorvient dans la réaction, en donnant lic-u à la formation du chlorhydrate de la substance (1). 2. Proceeds for 1.obt <: ntion of deriv-Js of arylcxylaobutyrlquos acids, sden claim It characterized in that it is made to add p-chloophenoxylsobutytic chloride act with 3-pyridylmethanol in presence of a solvent without the prescnco do substances captricca of hydrochloric acid, so that this dem1 <.! r intervenes in the reaction, giving lic-u to the formation of the hydrochloride of the substance (1). 3. Procédé pour l'obtention de dérivés des acides aryloxyisobutyriquGS, salon les rùven;:icatio; 1 et 2, carac- térisé en ce quoe l'on sst en cent<M:t le chlorure d'acide p-chlorophénoxy1sobut:'Jriuc avec le J-ßyriÓylL.lth3nol en l'absence de solvant et ca cr.uffnt la tout. 3. Process for obtaining derivatives of aryloxyisobutyriquGS acids, salon les rùven;: icatio; 1 and 2, charac- terized in that the p-chlorophenoxy1sobut acid chloride is in one hundred <M: t: 'Jriuc with J-ßyriÓylL.lth3nol in the absence of solvent and ca cr.uffnt the all. 4. Procédé pour 1 ot;.ntLcn de dàrivés dos acidas aryloxyisobuhyriqu*s, selon la revendication 1, caractérisé en ce que l'on met en ce?tact l'acide p-<hler;phànoxyiGeb- tyrique avec le 3-pyrldzlhol en pr±-3ience de catalyseu=r< EMI8.2 5. Procède pour 1'obtention de des acides EMI8.3 aryloxyîsobutyriques, sale-m la revendication 1, caractérisa en ce que l'on fait passer un courant d'aciàc 'shlorhydriqt3 à travers une solution du produit (1) dans dzs solvants EMI8.4 organiques. 4. Process for 1 ot; .ntLcn of aryloxyisobuhyriqu * s acidas derivatives, according to claim 1, characterized in that one puts in this? Tact p- <hler; phànoxyiGeb- tyric acid with 3-pyrldzlhol in pr ± -3ience of catalysteu = r < EMI8.2 5. Procedure for obtaining acids EMI8.3 aryloxyisobutyriques, sale-m of claim 1, characterized in that one passes a stream of aciàc 'shlorhydriqt3 through a solution of the product (1) in dzs solvents EMI8.4 organic.
BE739305D 1968-09-25 1969-09-24 3 pyridylemthanol p-chlorophenoxyisobutyrate com- - bining vasodilatory and anti-lipaemic activity BE739305A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
ES358856A ES358856A1 (en) 1968-09-25 1968-09-25 Procedure for the obtaining of derivatives of ariloxyisobutiric acids. (Machine-translation by Google Translate, not legally binding)

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BE739305A true BE739305A (en) 1970-03-02

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BE739305D BE739305A (en) 1968-09-25 1969-09-24 3 pyridylemthanol p-chlorophenoxyisobutyrate com- - bining vasodilatory and anti-lipaemic activity

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