DK159263B - PROCEDURE FOR THE PREPARATION OF ALFA ACYLOXYACETAMIDES - Google Patents
PROCEDURE FOR THE PREPARATION OF ALFA ACYLOXYACETAMIDES Download PDFInfo
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- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/12—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by halogen atoms or by nitro or nitroso groups
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Description
DK 159263 BDK 159263 B
Opfindelsen angår en særlig fremgangsmåde til fremstilling af hidtil ukendte a-acyloxyacetamider med den almene formel I (se krav 1), der kan anvendes som mellemprodukter til fremstilling af phenylethanol-5 aminer med den almene formel IIThe invention relates to a particular process for the preparation of novel α-acyloxyacetamides of general formula I (see claim 1) which can be used as intermediates for the preparation of phenylethanol-5 amines of general formula II
1 T1 T
\ vv CH - CH-, - N ,\ vv CH - CH-, - N,
V]fYV] fY
10 «,Λγ-1 R2 der har værdifulde farmakologiske egenskaber, især bron-cholytiske virkninger. Fremgangsmåden er ejendommelig 15 ved det i krav 1's kendetegnende del angivne.10 ', Λγ-1 R2 which has valuable pharmacological properties, especially broncholytic effects. The method is peculiar to the characterizing part of claim 1.
I de ovenfor anførte almene formler I og II betyder 1 R et chlor- eller bromatom, R2 en trifluormethylgruppe, et fluor- eller chloratom, 20 R3 en forgrenet alkylgruppe eller en cycloalkylgruppe hver med fra 3 til 5 carbonatomer og 4 R en COR gruppe, hvori R betegner en alkylgruppe med 1-4 carbonatomer eller en phenylgruppe.In the above general formulas I and II, 1 R represents a chlorine or bromine atom, R 2 is a trifluoromethyl group, a fluorine or chlorine atom, 20 R 3 is a branched alkyl group or a cycloalkyl group each having from 3 to 5 carbon atoms and 4 R a COR group, wherein R represents an alkyl group of 1-4 carbon atoms or a phenyl group.
Under de ved de ved definitionerne af grupperne 25 R3 og R4 tidligere nævnte betydninger kommer for R* i-sær betydningen en isopropyl-, isobutyl-, tert.butyl-, isopentyl-, neopentyl-, tert. pentyl-, cyclopropyl-, cyc-lobutyl- eller cyclopentylgruppe i betragtning, og eksempler på R4 er en acylrest af eddikesyre, propionsyre, 30 trimethyleddikesyre, valeriansyre og benzoesyre.Under the meanings previously mentioned by the definitions of groups 25 R3 and R4, for the R * in particular, is an isopropyl, isobutyl, tert-butyl, isopentyl, neopentyl, tert. pentyl, cyclopropyl, cyclo-butyl or cyclopentyl group under consideration, and examples of R 4 are an acyl residue of acetic acid, propionic acid, trimethyl acetic acid, valeric acid and benzoic acid.
Ifølge opfindelsen opnås de hidtil ukendte a-acyl-According to the invention, the novel α-acyl
oxyacetamider med den ovenfor anførte almene formel Ioxyacetamides of the above general formula I
ved omsætning af et 4-amino-benzaldehyd med den almene for- 1 2 35 mel III (se krav 1 ), hvori R og R er som defineret tidligere, med en isonitril med den almene formel IV (se krav 1), hvori R er defineret som tidligere, og med en carboxylsyre med den almene formel V (se krav 1 ), hvori 2 4by reacting a 4-amino-benzaldehyde with the general formula III (see claim 1) wherein R and R are as previously defined with an isonitrile of the general formula IV (see claim 1) wherein R is defined as before, and with a carboxylic acid of general formula V (see claim 1), wherein
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R er defineret som tidligere.R is defined as before.
Til fremstilling af en phenylethanolamin med den almene formel II reduceres et således opnået a-acyloxy-acetamid med den almene formel I, der også som råprodukt 5 kan omsættes videre,med hydrid, f.eks. med et metalhy-drid eller et komplekst metalhydrid, såsom boran/tetra-hydrofuran eller lithiumaluminiumhydrid.To prepare a phenylethanolamine of the general formula II, a thus obtained α-acyloxy-acetamide of the general formula I, which can also be further reacted as crude product 5, is reduced with hydride, e.g. with a metal hydride or a complex metal hydride such as borane / tetrahydrofuran or lithium aluminum hydride.
Omsætningen af et 4-amino-benzaldehyd med den almene formel III med en isonitril med den almene formel 10 IV og med en carboxylsyre med den almene formel V gennemføres hensigtsmæssigt i et egnet opløsningsmiddel, - såsom methylenchlorid, chloroform, benzen, ether, tetra-hydrofuran eller dioxan ved lave temperaturer, f.eks. ved temperaturer mellem -20 og 75°C, hensigtsmæssigt 15 dog stuetemperatur. Omsætningen gennemføres dog fortrinsvis på den måde, at der enten samtidigt fra hver sin tildrypningstragt tildryppes en forbindelse med den almene formel IV og en carboxylsyre med den almene formel V til en opløsning af et aldehyd med den almene 20 formel III eller til en opløsning af en isonitril med den almene formel IV og et aldehyd med den almene formel III tildryppes en carboxylsyre med den almene formel V inden for flere tårner, f.eks. 5-10 timer, alt dette under omrøring og ved stuetemperatur, og derpå omrøres 25 i yderligere 10 til 165 timer.The reaction of a 4-amino-benzaldehyde of general formula III with an isonitrile of general formula 10 and with a carboxylic acid of general formula V is conveniently carried out in a suitable solvent, such as methylene chloride, chloroform, benzene, ether, hydrofuran or dioxane at low temperatures, e.g. at temperatures between -20 and 75 ° C, conveniently, however, room temperature. However, the reaction is preferably carried out in that either a compound of the general formula IV and a carboxylic acid of the general formula V is added simultaneously from each droplet funnel to a solution of an aldehyde of the general formula III or to a solution of a isonitrile of the general formula IV and an aldehyde of the general formula III, a carboxylic acid of the general formula V is added within several towers, e.g. 5-10 hours, all this while stirring and at room temperature, and then stirring for an additional 10 to 165 hours.
Reduktionen af et opnået a-acyloxy-acetamid med den almene formel I med et hydrid gennemføres fortrinsvis i et egnet opløsningsmiddel, såsom ether, tetrahy-drofuran eller dioxan ved lave eller let forhøjede 30 temperaturer, f.eks. ved temperaturer mellem 0 og 100°c, hensigtsmæssigt dog ved reaktionsblandingens kogetemperatur. Særlig fordelagtig gennemføres reduktionen dog med boran/tetrahydrofuran ved kogetemperaturen af det som opløsningsmiddel anvendte tetrahydrofuran.The reduction of a obtained α-acyloxy-acetamide of the general formula I with a hydride is preferably carried out in a suitable solvent such as ether, tetrahydrofuran or dioxane at low or slightly elevated temperatures, e.g. at temperatures between 0 and 100 ° C, however convenient at the boiling temperature of the reaction mixture. However, the reduction in borane / tetrahydrofuran is particularly advantageous at the boiling temperature of the tetrahydrofuran used as the solvent.
35 Isoleringen af det ønskede slutprodukt med den almene formel II sker hensigtsmæssigt med vandige baser, f.eks. med vand/ammoniak, hvorved en eventuelt stadig tilstedeværende a-acyloxygruppe fraspaltes.The isolation of the desired final product of general formula II is conveniently carried out with aqueous bases, e.g. with water / ammonia, thereby cleaving off any possibly a-acyloxy group.
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En således opnået phenylethanolamin med den almene formel II lader sig om ønsket derpå med en uorganisk eller organisk syre overføre i dens fysiologisk forligelige 5 syreadditionssalt med den pågældende syre. Som syre kommer hertil f.eks. saltsyre, hydrogenbromid, svovlsyre, phosphorsyre, mælkesyre, vinsyre, citronsyre, fumar-syre eller maleinsyre i betragtning.A phenylethanolamine thus obtained of the general formula II can, if desired, be transferred with an inorganic or organic acid into its physiologically compatible acid addition salt with the acid in question. As an acid addition, e.g. hydrochloric acid, hydrogen bromide, sulfuric acid, phosphoric acid, lactic acid, tartaric acid, citric acid, fumaric acid or maleic acid under consideration.
De som udgangsmaterialer anvendte forbindelser 10 med de almene formler IV og V er kendte fra litteraturen.The compounds 10 of the general formulas IV and V used as starting materials are known from the literature.
Et som udgangsprodukt anvendt aldehyd med den almene formel III opnås f.eks. ved reduktion af et tilsvarende 4-amino-benzoesyrehalogenid eller -ester og påføl-15 gende oxidation af den i påkommende tilfælde opnåede benzylalkohol med brunsten.An aldehyde of the general formula III used as a starting product is obtained e.g. by reduction of a corresponding 4-amino-benzoic acid halide or ester and subsequent oxidation of the benzyl alcohol obtained with tartar as appropriate.
Fra litteraturen er der allerede kendt en fremgangsmåde til fremstilling af phenylethanolaminer med den almene formel II, der er kendetegnet ved, at et 20 glycolsyreamid med den almene formel VIFrom the literature, there is already known a process for the preparation of phenylethanolamines of the general formula II, characterized in that a glycolic acid amide of the general formula VI
?H h 1 * “ C° " 3? H h 1 * “C °” 3
I VII VI
25 H2N"lf ir 12 3 hvori R , R og R er defineret som tidligere^reduceres med et kompleks metalhydrid.Wherein R, R and R are as previously defined are reduced by a complex metal hydride.
Denne fremgangsmåde har dog den ulempe, at det 30 hertil som udgangsprodukt nødvendige glycolsyreamid kun vanskeligt lader sig fremstille.However, this process has the disadvantage that the glycolic acid amide needed for this is only difficult to produce.
De med den omhandlede nye fremgangsmåde opnåede gode udbytter kan ikke forudses af en fagmand, da det fra litteraturen er kendt (se J.Amer. chem. Soc. (57 35 1499-1500 (1945)), at Passerini-reaktionen ikke lader sig gennemføre med sterisk blokerede og med α,3-umættede carbonylforbindelser. Her forklares a,3-umættede carbonylforbindelsers, f.eks. crotonaldehyds, ureaktivitet over for Passerini-reaktionen ved neutralisationen 4The good yields obtained with the present process cannot be predicted by one skilled in the art, as it is known from the literature (see J. Ammer. Chem. Soc. (57 35 1499-1500 (1945)) that the Passerini reaction is not feasible conduct with sterically blocked and with α, 3-unsaturated carbonyl compounds, which explain α, 3-unsaturated carbonyl compounds, eg crotonaldehyde, unreactivity to the Passerini reaction by neutralization 4
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af carbonylfunktionens elektroniske centrum på grund af de mesomere grænsestrukturer 5 S '© ΐΘof the electronic center of the carbonyl function due to the mesomer boundary structures 5 S '© ΐΘ
R-CH=CH-C-R <-> R-CH-CH=C-RR-CH = CH-C-R <-> R-CH-CH = C-R
altså på grund af den elektronleverende virkning fra en nabogruppe.thus due to the electron-providing effect of a neighboring group.
Yderligere er det kendt, at aminogruppen i o- eller 10 p-positionen af en phenylkerne har en stærk elektronleverende virkning.Further, it is known that the amino group at the o- or 10-p position of a phenyl nucleus has a strong electron-delivery effect.
Fagmanden måtte derfor forvente, at det elektroniske centrum i carbonylfunktionen af et 4-aminobenzaldéhyd med den almene formel III på grund af den mesomere 15 grænsestruktur · med den almene formel Illa tt Illa ΈΓ ΈΓ deaktiveres, og at Passerinireaktionen dermed ikke er tilgængelig. Dette er overraskende ikke tilfældet.Therefore, one skilled in the art would expect that the electronic center of the carbonyl function of a 4-aminobenzaldehyde of the general formula III due to the someric 15 boundary structure · of the general formula Illa tt Illa ΈΓ ΈΓ is deactivated and thus the Passerini reaction is not available. This is surprisingly not the case.
25 De efterfølgende eksempler belyser opfindelsen nærmere:The following examples further illustrate the invention:
Eksempel 1 a-Acetoxy-a-(4-amino-3,5-dichlor-phenyl)-N-tert.butyΙ-ΙΟ acetamid.Example 1 α-Acetoxy-α- (4-amino-3,5-dichloro-phenyl) -N-tert-butyl-ΙΟ acetamide.
Til en opløsning af 3,8 g (0,02 mol) 4-amino-3,5-dichlor-benzaldehyd i 50 ml absolut methylenchlorid dryppes under omrøring ved stuetemperatur 3,32 g (0,04 mol) tert.butylisonitril og 4,8 g (0,08 mol) 35 iseddike med samme hastighed fra to adskilte tildryp-ningstragte i løbet af 8 timer. Derpå inddampes den opnåede opløsning til halvdelen og afkøles. Det herved udfældede,ikke-omsatte 4-amino-3,5-dichlor-benzaldehyd suges af, og filtratet inddampes påny til halvdelen.To a solution of 3.8 g (0.02 mol) of 4-amino-3,5-dichlorobenzaldehyde in 50 ml of absolute methylene chloride is added dropwise with stirring at room temperature 3.32 g (0.04 mol) of tert.butyl isonitrile and 4 , 8 g (0.08 mole) 35 vinegar at the same rate from two separate dropping funnels over 8 hours. Then the resulting solution is evaporated to half and cooled. The precipitated, unreacted 4-amino-3,5-dichlorobenzaldehyde is thereby suctioned off and the filtrate is again evaporated to half.
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Til den opnåede blanding sættes det samme rumfang diisopropylether, hvo-rved det ønskede produkt udkrystalliserer, suges af, og vaskes méd diisopropylether.To the mixture obtained is added the same volume of diisopropyl ether, whereby the desired product crystallizes, is suctioned off and washed with diisopropyl ether.
5 Smp.: 175-176°C.Mp: 175-176 ° C.
Eksempel 2 a-Acetoxy-α-(4-amino-3,5-dichlor-phenyl)-N-tert.butyl-acetamid.Example 2 α-Acetoxy-α- (4-amino-3,5-dichloro-phenyl) -N-tert-butyl-acetamide.
10 Til en opløsning af 30 g (0,16 mol) 4-amino-3,5- dichlor-benzaldehyd i 280 ml methyienchlorid sættes 45 ml tert.butylisocyanid, og derpå tildryppes under omrøring og ved stuetemperatur ca.40 ml. iseddike i løbet af 16 timer. Derefter omrøres i yderligere 4 timer og 15 inddampes så længe i vakuum, at de første krystaller udfældes. Efter afkøling til 0°C afsuges det udfældede ikke-omsatte 4-amino-3,5-dichlor-benzaldehyd. Dette kan direkte omsættes påny. Filtratet tilsættes n-hexan, hvorved det ønskede produkt udfældes. Bundfaldet afsuges, 20 vaskes med n-hexan og tørres.To a solution of 30 g (0.16 mol) of 4-amino-3,5-dichlorobenzaldehyde in 280 ml of methylene chloride is added 45 ml of tert-butyl isocyanide and then is added dropwise with stirring and at room temperature about 40 ml. glacial vinegar over 16 hours. Then stir for a further 4 hours and evaporate for a long time in vacuo to precipitate the first crystals. After cooling to 0 ° C, the precipitated unreacted 4-amino-3,5-dichloro-benzaldehyde is aspirated. This can be directly reacted again. The filtrate is added to n-hexane to precipitate the desired product. The precipitate is aspirated, washed with n-hexane and dried.
Smp.: 175-176°C.Mp: 175-176 ° C.
Eksempel 3 1-(4-Amino-3,5-dichlor-phenyl)-2-tert.butylamino-ethanoL 25 Til en opløsning af 4,01 g a-acetoxy-a-(4-amino- 3,5-dichlor-phenyl)-N-tert.butylacetamid i 50 ml absolut tetrahydrofuran sættes 100 ml af en 1-molær opløsning af faxan i tetrahyåxfizan. Efter 2 timers cpranrning under tilba^swaling ind-darpes (fer, 100 mL «d tilsættes, og blandingen gares sur mad saltsyre til jH 2. Den 30 vandige fase vaskes med ethylacetat, gøres derpå alkalisk med ammoniak og ekstraheres med methyienchlorid. Efter inddampningen af den organiske fase opnås hydrochloridet fra isopropanol ved tilsætning af etherholdig saltsyre. Hydrochloridets smp.: 174-175°C.Example 3 1- (4-Amino-3,5-dichloro-phenyl) -2-tert-butylamino-ethanol To a solution of 4.01 g of α-acetoxy-α- (4-amino-3,5-dichloro) -phenyl) -N-tert-butylacetamide in 50 ml of absolute tetrahydrofuran is added 100 ml of a 1-molar solution of faxane in tetrahydroxfizane. After 2 hours of cooling under reflux, immerse (fer, 100 mL) d and add the acidic acid hydrochloric acid to 2H. The aqueous phase is washed with ethyl acetate, then made alkaline with ammonia and extracted with methylene chloride. of the organic phase, the hydrochloride is obtained from isopropanol by the addition of ethereal hydrochloric acid, mp: 174-175 ° C.
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Eksempel 4 a-Acetoxy-α-(4-amino-3-chlor-5-trifluormethyl-phenyl)-eddikesyre-tert.butylamid.Example 4 α-Acetoxy-α- (4-amino-3-chloro-5-trifluoromethyl-phenyl) -acetic acid tert-butylamide.
Til en opløsning af 4,47 g (20 mmol) 4-amino-3-chlor-5-trifluormethyl-benzaldehyd i 50 ml methylenchlo-To a solution of 4.47 g (20 mmol) of 4-amino-3-chloro-5-trifluoromethyl-benzaldehyde in 50 ml of methylene chloride.
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e rid tildryppes ved stuetemperatur under omrøring 3/32 g (40 mmol) tert.butylisonitril og 4f8 g (80 mmol) iseddike samtidigt i løbet af 5 timer,og derpå amrøres blandingen 5 i 65 timer ved stuetemperatur. Efter fjernelse af opløsningsmidlet i vakuum opløses resten i ether, vaskes efter hinanden med vand og en mættet natriurohydrogen-carbonatopløsning, tørres over magnesiumsulfat og inddampes i vakuum til tørhed. Resten chromatograferes på 10 en kiselgelsøjle med methylenchlorid som elueringsmiddel.The mixture is dropped at room temperature with stirring 3/32 g (40 mmol) of tert.butylisonitrile and 4f8 g (80 mmol) of glacial acetic acid at the same time over 5 hours, and then the mixture is stirred 5 for 65 hours at room temperature. After removing the solvent in vacuo, the residue is dissolved in ether, washed successively with water and a saturated sodium hydrogen carbonate solution, dried over magnesium sulfate and evaporated in vacuo to dryness. The residue is chromatographed on a silica gel column with methylene chloride as the eluent.
De fraktioner, der indeholder den ønskede forbindelse, samles og inddampes, og resten krystalliseres i ether.The fractions containing the desired compound are collected and evaporated and the residue is crystallized in ether.
Smp.: 155-156°C.Mp: 155-156 ° C.
15 Eksempel 5 1-(4-Amino-3-chlor-5-trifluormethyl-phenyl)-2-tert.-butylamino-ethanol-hydrochlorid.Example 5 1- (4-Amino-3-chloro-5-trifluoromethyl-phenyl) -2-tert-butylamino-ethanol hydrochloride.
2 g (5,4 mmol) a-acetoxy-α-(4-amino-3-chlor-5-trifluormethyl-phenyl)-eddikesyre-tert.butylamid oplø-20 ses i 15 ml absolut tetrahydrofuran og sættes under nitrogen på én gang til 27 ml af en 1-molar opløsning af boran i tetrahydrofuran. Efter 4 timers kogning under tilbagesvaling sættes der yderligere 15 ml l-mo]ær boranopløsning til og opvarmes yderligere i 2 timer 25 under tilbagesvaling. Derefter nedbrydes overskuddet af boran med acetone. Borkomplekset opløses med vand, og derpå afdampes opløsningsmidlet i vakuum. Den vandige destillationsrest gøres sur med 2n-saltsyre, gøres atter alkalisk med ammoniak og ekstraheres med ether.2 g (5.4 mmol) of α-acetoxy-α- (4-amino-3-chloro-5-trifluoromethyl-phenyl) -acetic acid tert-butylamide are dissolved in 15 ml of absolute tetrahydrofuran and placed under nitrogen on one to 27 ml of a 1-molar solution of borane in tetrahydrofuran. After 4 hours of refluxing, an additional 15 ml of 1-mo borane solution is added and further heated for 2 hours under reflux. Then the excess of borane is degraded with acetone. The boron complex is dissolved with water and then the solvent is evaporated in vacuo. The aqueous distillation residue is acidified with 2N hydrochloric acid, again made alkaline with ammonia and extracted with ether.
30 Etherekstrakten ekstraheres med 0,5n saltsyre, syreopløsningen vaskes med ether, gøres alkalisk med ammoniak og ekstraheres påny med ether. Etherekstrakten vaskes med vand, tørres med magnesiumsulfat og inddampes i vakuum. Den olieagtige inddampningsrest opløses i 35 ether og gøres sur med etherholdig saltsyre. De udfældede krystaller suges af og vaskes med ether.The ether extract is extracted with 0.5n hydrochloric acid, the acid solution is washed with ether, made alkaline with ammonia and extracted again with ether. The ether extract is washed with water, dried over magnesium sulfate and evaporated in vacuo. The oily residue is dissolved in 35 ether and acidified with ethereal hydrochloric acid. The precipitated crystals are sucked off and washed with ether.
Smp.: 192-193°C.Mp: 192-193 ° C.
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Eksempel 6 a-Acetoxy-α-(4-amino-3,5-dichlor-phenyl)-N-tert.butyl-acetamid.Example 6 α-Acetoxy-α- (4-amino-3,5-dichloro-phenyl) -N-tert-butyl-acetamide.
5 Til en opløsning af 14,1 g (0,08 mol) 4-amino-3,5- dichlor-benzaldehyd i 60 ml methylenchlorid tilsættes ved stuetemperatur og under omrøring 3,6 g (0,06 mol) eddikesyre og 2,5 g (0,03 mol) tert.butylisonitril.To a solution of 14.1 g (0.08 mol) of 4-amino-3,5-dichlorobenzaldehyde in 60 ml of methylene chloride is added at room temperature and with stirring 3.6 g (0.06 mol) of acetic acid and 2, 5 g (0.03 mole) of tert.butylisonitrile.
Derpå opvarmes reaktionsblandingen i 3 timer under til-10 bagesvaling. Efter at den ovennævnte operation (tilsætning af eddikesyre, tert.butylisonitril og opvarmning under tilbagesvaling) er gentaget fire gange, hældes reaktionsblandingen over i kold 2N natronlud, og den organiske fase isoleres. Efter vask med vand og tørring 15 af den organiske fase over natriumsulfat inddampes der i vakuum, og resten krystalliseres af methylenchlorid/hexan.Then, the reaction mixture is heated for 3 hours under reflux. After the above operation (addition of acetic acid, tert-butyl isonitrile and reflux heating) is repeated four times, the reaction mixture is poured into cold 2N sodium hydroxide solution and the organic phase is isolated. After washing with water and drying the organic phase over sodium sulfate, evaporate in vacuo and the residue is crystallized by methylene chloride / hexane.
Smp. 175-176°C.Mp. 175-176 ° C.
Eksempel 7 20 a-(4-Amino-3,5-dichlor-phenyl)-a-benzoyloxy-N-tert.-butylacetamid.Example 7 α- (4-Amino-3,5-dichloro-phenyl) -α-benzoyloxy-N-tert.-butylacetamide.
Fremstillet analogt med eksempel 4 af 4-amino- 3.5- dichlor-benzaldehyd, tert.butylisonitril og benzoesyre i chloroform og ved tilbagesvalingstempera- 25 tur.Prepared analogously to Example 4 of 4-amino-3,5-dichloro-benzaldehyde, tert-butylisonitrile and benzoic acid in chloroform and at reflux temperature.
Smp.: 189-192°C (sintrer fra 185°C).Mp: 189-192 ° C (sintering from 185 ° C).
Eksempel 8 a-(4-Amino-3,5-dichlor-phenyl)-a-valeroyloxy-N-tert.-30 butylacetamid.Example 8 α- (4-Amino-3,5-dichloro-phenyl) -α-valeroyloxy-N-tert-butylacetamide.
Fremstillet analogt med eksempel 4 af 4-amino-3,5-dichlor-benzaldehyd, tert.butylisonitril og valerian-syre.Prepared analogously to Example 4 of 4-amino-3,5-dichloro-benzaldehyde, tert-butylisonitrile and valeric acid.
Smp.: 95-98°C.Mp: 95-98 ° C.
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Eksempel 9 1- (4-Amino-3,5-dichlor-phenyl)-2-tert.butylamino-ethanoL Fremstillet analogt med eksempel 3 af a-(4-amino- 3.5- dichlor-phenyl)-a-benzoyloxy-N-tert.butylacetamid 8Example 9 1- (4-Amino-3,5-dichloro-phenyl) -2-tert-butylamino-ethanol Prepared analogously to Example 3 of α- (4-amino-3,5-dichloro-phenyl) -α-benzoyloxy-N -butyl acetamide 8
DK 159263 BDK 159263 B
og lithiumaluminiumhydrid i tetrahydrofuran.and lithium aluminum hydride in tetrahydrofuran.
Hydrochloridets smp.: T74-175°C.The hydrochloride mp: T74-175 ° C.
^ Eksempel 10 1-(4-Amino-3,5-dichlor-phenyl)-2-tert.butylamino-ethanol.Example 10 1- (4-Amino-3,5-dichloro-phenyl) -2-tert-butylamino-ethanol.
Fremstillet af 4-amino-3,5-dichlor-benzaldehyd, tert.butylisonitril og valeriansyre analogt med eksemplerne 2 og 5 uden isolering af det dannede a-(4-amino- 10 3/5-dichlorphenyl)-N-tert.butyl-a-valeroyloxy-acetamid.Prepared from 4-amino-3,5-dichloro-benzaldehyde, tert-butylisonitrile and valeric acid analogous to Examples 2 and 5 without isolation of the resulting α- (4-amino-3/5-dichlorophenyl) -N-tert.butyl -A-valeroyloxy-acetamide.
Hydrochloridets smp.: 174-175°C.The hydrochloride mp: 174-175 ° C.
Analogt med de foregående eksempler blev de følgende forbindelser fremstillet:By analogy to the preceding examples, the following compounds were prepared:
1-(4-amino-3-brom-5-fluor-phenyl)-2-tert.butylamino-Ί 5 ethano1-hydrochlorid, smp.: 207-208°C1- (4-Amino-3-bromo-5-fluoro-phenyl) -2-tert-butylamino-ethanoyl hydrochloride, mp: 207-208 ° C
1-(4-amino-3-chlor-5-fluor-phenyl)-2-cyclopropylamino-ethanol-hydrochlorid, smp.: 175-177°C1- (4-Amino-3-chloro-5-fluoro-phenyl) -2-cyclopropylamino-ethanol hydrochloride, mp: 175-177 ° C
20 1-(4-amino-3-chlor-5-fluor-phenyl)-2-tert.butylamino-1- (4-Amino-3-chloro-5-fluoro-phenyl) -2-tert-butylamino
ethanol-hydrochlorid, smp.: 206-208°Cethanol hydrochloride, mp: 206-208 ° C
1-(4-amino-3-chlor-5-trifluormethyl-phenyl)-2-cyclo-butylamino-ethano1-hydrochlorid,1- (4-amino-3-chloro-5-trifluoromethyl-phenyl) -2-cyclo-butylamino-ethano1, hydrochloride,
25 smp.: 177-178°CMp: 177-178 ° C
1-(4-amino-3-brom-5-fluor-phenyl)-2-cyclobutylamino-ethanol-hydrochlorid, smp.: 164-166°C1- (4-Amino-3-bromo-5-fluoro-phenyl) -2-cyclobutylamino-ethanol hydrochloride, mp: 164-166 ° C
1-(4-amino-3-chlor-5-trifluormethyl-phenyl)-2-tert.-3 0 pentylamino-ethanol-hydrochlorid, smp.: 176-178°C (sønderdeling) 1-(4-amino-3-chlor-5-fluor-phenyl)-2-isopropylamino- ethanol-hydrochlorid, smp.: 152-154°C (sønderdeling) 35 1-(4-amino-3-brom-5-trifluormethyl-phenyl)-2-cyclopen- tylamino-ethanol, smp.: 100-102,5°C (sønderdeling).1- (4-Amino-3-chloro-5-trifluoromethyl-phenyl) -2-tert-pentylamino-ethanol hydrochloride, mp: 176-178 ° C (dec.) 1- (4-amino-3 -chloro-5-fluoro-phenyl) -2-isopropylamino-ethanol hydrochloride, mp: 152-154 ° C (dec.) 1- (4-amino-3-bromo-5-trifluoromethyl-phenyl) -2- cyclopentylamino-ethanol, mp: 100-102.5 ° C (dec.).
Claims (3)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FI790067A FI59396C (en) | 1979-01-10 | 1979-01-10 | PROCEDURE FOR THE FRAMSTATION OF AV 2- (4-AMINO-3,5-DICHLOROPHENYL) -2-CARBOXY-N-TERT-BUTYL ACETAMIDER |
| FI790067 | 1979-01-10 | ||
| DE2942723 | 1979-10-23 | ||
| DE19792942723 DE2942723A1 (en) | 1979-10-23 | 1979-10-23 | Prepn. of broncholytic phenyl-ethanolamine derivs. - via new 2-acyloxy-2-phenyl-acetamide derivs. |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DK8480A DK8480A (en) | 1980-07-11 |
| DK159263B true DK159263B (en) | 1990-09-24 |
| DK159263C DK159263C (en) | 1991-02-18 |
Family
ID=25781629
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK008480A DK159263C (en) | 1979-01-10 | 1980-01-08 | PROCEDURE FOR THE PREPARATION OF ALFA ACYLOXYACETAMIDES |
| DK517289A DK159262C (en) | 1979-01-10 | 1989-10-18 | METHOD OF PREPARING PHENYLETHANOLAMINES |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK517289A DK159262C (en) | 1979-01-10 | 1989-10-18 | METHOD OF PREPARING PHENYLETHANOLAMINES |
Country Status (18)
| Country | Link |
|---|---|
| AT (1) | AT367398B (en) |
| BG (1) | BG33584A3 (en) |
| CA (1) | CA1146958A (en) |
| CH (1) | CH645611A5 (en) |
| CS (1) | CS214689B2 (en) |
| DD (2) | DD156179A5 (en) |
| DK (2) | DK159263C (en) |
| ES (1) | ES8102547A1 (en) |
| GR (1) | GR74391B (en) |
| HU (2) | HU188207B (en) |
| NL (1) | NL8000126A (en) |
| NO (2) | NO148522C (en) |
| PL (2) | PL126876B1 (en) |
| PT (1) | PT70661A (en) |
| RO (1) | RO78779A (en) |
| SE (2) | SE447102B (en) |
| SU (1) | SU884563A3 (en) |
| YU (1) | YU4880A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR102020008433A2 (en) | 2020-04-28 | 2021-11-03 | Universidade Federal Do Parana | ARTHROPOD REPELLENTS OBTAINED FROM THE CHEMICAL TRANSFORMATION OF LACTIC ACID, LACTATES OR OTHER LACTIC ACID DERIVATIVES |
-
1979
- 1979-12-24 BG BG046027A patent/BG33584A3/en unknown
- 1979-12-28 NO NO794314A patent/NO148522C/en unknown
-
1980
- 1980-01-04 GR GR60893A patent/GR74391B/el unknown
- 1980-01-04 SU SU802863255A patent/SU884563A3/en active
- 1980-01-04 AT AT0003380A patent/AT367398B/en not_active IP Right Cessation
- 1980-01-07 PT PT70661A patent/PT70661A/en not_active IP Right Cessation
- 1980-01-07 CS CS80164A patent/CS214689B2/en unknown
- 1980-01-07 CH CH6680A patent/CH645611A5/en not_active IP Right Cessation
- 1980-01-08 DD DD80227454A patent/DD156179A5/en unknown
- 1980-01-08 DD DD80218350A patent/DD150198A5/en unknown
- 1980-01-08 CA CA000343261A patent/CA1146958A/en not_active Expired
- 1980-01-08 DK DK008480A patent/DK159263C/en not_active IP Right Cessation
- 1980-01-08 YU YU00048/80A patent/YU4880A/en unknown
- 1980-01-09 NL NL8000126A patent/NL8000126A/en not_active Application Discontinuation
- 1980-01-09 HU HU8330A patent/HU188207B/en unknown
- 1980-01-09 SE SE8000175A patent/SE447102B/en not_active IP Right Cessation
- 1980-01-09 PL PL1980221288A patent/PL126876B1/en unknown
- 1980-01-09 HU HU8041A patent/HU181681B/en unknown
- 1980-01-09 PL PL1980234384A patent/PL126046B1/en unknown
- 1980-01-09 RO RO8099824A patent/RO78779A/en unknown
- 1980-01-09 ES ES487548A patent/ES8102547A1/en not_active Expired
-
1982
- 1982-09-17 NO NO823159A patent/NO148997C/en unknown
-
1984
- 1984-11-09 SE SE8405631A patent/SE452979B/en not_active IP Right Cessation
-
1989
- 1989-10-18 DK DK517289A patent/DK159262C/en not_active IP Right Cessation
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