NO742946L - - Google Patents
Info
- Publication number
- NO742946L NO742946L NO742946A NO742946A NO742946L NO 742946 L NO742946 L NO 742946L NO 742946 A NO742946 A NO 742946A NO 742946 A NO742946 A NO 742946A NO 742946 L NO742946 L NO 742946L
- Authority
- NO
- Norway
- Prior art keywords
- acid
- formula
- acid addition
- addition salts
- residue
- Prior art date
Links
- 239000002253 acid Substances 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 150000007513 acids Chemical class 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 239000007858 starting material Substances 0.000 claims description 2
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 claims 2
- 125000002960 margaryl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 230000003287 optical effect Effects 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- -1 benzo2syra Chemical compound 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 229910052987 metal hydride Inorganic materials 0.000 description 2
- 150000004681 metal hydrides Chemical class 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- LFMQNMXVVXHZCC-UHFFFAOYSA-N 1,3-benzothiazol-2-yl n,n-diethylcarbamodithioate Chemical compound C1=CC=C2SC(SC(=S)N(CC)CC)=NC2=C1 LFMQNMXVVXHZCC-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- LUJMEECXHPYQOF-UHFFFAOYSA-N 3-hydroxyacetophenone Chemical class CC(=O)C1=CC=CC(O)=C1 LUJMEECXHPYQOF-UHFFFAOYSA-N 0.000 description 1
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
- YIUIVFFUEVPRIU-UHFFFAOYSA-N 8-chlorotheophylline Chemical compound O=C1N(C)C(=O)N(C)C2=NC(Cl)=N[C]21 YIUIVFFUEVPRIU-UHFFFAOYSA-N 0.000 description 1
- 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 241000220317 Rosa Species 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 244000126014 Valeriana officinalis Species 0.000 description 1
- 235000013832 Valeriana officinalis Nutrition 0.000 description 1
- 150000008062 acetophenones Chemical class 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229960004050 aminobenzoic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- MOOAHMCRPCTRLV-UHFFFAOYSA-N boron sodium Chemical compound [B].[Na] MOOAHMCRPCTRLV-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000003245 coal Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- GATNOFPXSDHULC-UHFFFAOYSA-N ethylphosphonic acid Chemical compound CCP(O)(O)=O GATNOFPXSDHULC-UHFFFAOYSA-N 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 235000016788 valerian Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/08—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/02—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen
- C07C69/22—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen having three or more carbon atoms in the acid moiety
- C07C69/24—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen having three or more carbon atoms in the acid moiety esterified with monohydroxylic compounds
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Description
"Analogifremgangsmåte £or freraotilling av 1-(ra-acylokoyf©nyl) -1 -hydroksy-2-BT-alIcylamino-.
:atener."
Danne oppfinnelse angår cn analogifremgangsmåte for framatilling av l-(ra-acyloksy£enyl)°l-hydrokoy-2HSf-alkylamino*-etanQr med den
. generelle formelt
hvor R betyr en alkylrost med 3 til 19 karbonatomer, og &2betyr metyl eller etyl, og syreaddlsjonssaltar derav.
Forbindelsene med formel I har et asymmetrisk karbonatora og kan derfor foreligge i form av raceraater eller i form av optisk aktive forbindelser.
De nye forbindelser fremstilles i henhold til oppfinnelsen ved re-duksjon av tilsvarende acetofenonderivater med formelent
hvor R. og or som ovanfor angitt, og betyr hydrogen oller en eventuelt substituert benzylrest. Bensylresten kan f.eks. være substituert med alkyl--ellar alkoksygrupper eller et halogenatora, særlig et kloratom. Redaksjonen forståa ved katalytisk hydrogenering atad kjønto hydrogonaringskatalyoatorer, oom f.oke. Pd, Pt, Mi eller mad komplokss metallhydrider ned liten reduksjonskraft, som f.oko. natriuraborhydrid. Hvis reoton £1^^©tyr en bensylrest, fjernes den samtidig foycirogonolytiok vod don katalytiske hydrogen-er ing. Hvis roduksj 0:10:1 av kotogruppan foretas mod komplekse metallhydrider, avopaltaDbenzylgruppen dereftor ved katalytisk hydrogenering. 1 De utgangsforbindelosr rcsd den generell©formal II som anvendes ved f r omgang ømå ten, kasi fremstilles ved aeylering av m-hydroksy-acetofenoner med formalen3 hvor R2 og R3har don ovanfor angitte betydning, med et syreklorid med formalens
hvor R^har den ovenfor angitte betydning, og eventuelt påfølgende
selektiv hydrogenolyse av Itenzylgruppen. Racemater av forbindelser med formel Z spaltes eventuelt på vanlig måte i antipodene.
De nye forbindelser med formel I er baser og kan på vanlig måte overføres til de fysiologisk forlikelige syreaddisjonssalter.
Syrer som er egnet til saltdannalse, er f.eks. mineralsyrer så
som saltsyre, bromhydrogensyre, jodhydrogensyre, fluorhydrogensyre, svovelsyre, fosforsyre, salpetersyre eller organiske syrer så
som eddiksyre, propionsyra, smørsyre, kapronsyre, kaprinoyre, valeriansyre, oksalsyre, malonsyre, ravoyre, maleinsyre, fumarsyra, melkesyre, vinsyre, sitronsyre, benzo2syra, p-hydroksybansoesyre, p-aminobenzoesyre, ftalsyro, kanelsyre, salicylsyre, askorbinsyre, metansulfonsyra, etanfosfonsyre, 8-klorteofyllin eller lignende.
De nye forbindelser msd dan generelle formel I og deres syreaddi-sjoneaalter utmerker seg ved verdifulle terapeutisk© egenskaper. De egner særlig som aktive stoffer i hjerte- og kretsløpmidler, og kan derfor anvendes tii behandling av hjertesvikt eller krétsløps-1idelser.
Forbindelsene med den generelle formel 1 og deree eyreaddis-jonsoal-ter kan anvendes enteralt eller parenfceralt. De anvendes i doser på 5 til 100 mg. Forbiii&alsene med formal I og deres syreaddisjonssalter kan også anvendoc samman med aktive stoffer av andre typer.
Egnede galeniske tilbsrodelsasformer er f.eks. tabletter, kapslar, stikkpiller, oppløsninger, omulojoner aerosoler eller pulvere, og for fremstilling av disse kan man anvende de vanlige galeniske hjelpestoffer, beeremidlor, sprengmidler eller smØremidler eller stoffer.som.gir en depotvirkning. Fremstilling av slike galeniske tilberedelseaformsr foretan på vanlig måte efter kjente tilbered-elsesmetoder.
De følgende eksempler skal t;jene til å illustrere oppfinnelsen ytter-ligere.
Eksempel 1
1-( m- stearvlokayfenvl) - l- hydroksv- 2HK- etglamino- etanhy<iroklorid.
a) ' m- Btearylokflv- torffi- atylaminoraTO . ■...
Ell en oppløi&nlhg av 53,0 g (0,25 mol) rh^yfiroksy-c^-etylamind- /.
nrratofénon»Hci;i ICO es?, trifluoreddifcriyro oattoo dråpavis uiicloar ... ; omrøring vad 30 C 94,5 (j,(0,312. mol)', stoorylklorid.. perafter hol-. Cfåp ,roaksjonjjøfLandiAg&i i 5 minutter. vad•'. §DQC og : innrøres uten avkjøling, i .i: lit$r otylacatat.. DarVoi" okjor krystalliBasjon av forbindelsen., KrystP.IA^sis eveugoaog vfce&oo sæad etylacatat... '.Utbytta: .id8 'g, .8S,C;\; dat teoret:lr£c?L. Caoltepunkt: 195°c Xox»'»?: ciÆcryotailis.-.\rjj'osi-ffrai etandl).
-J) 1 - ( m- Btøarvlokev£e:.;.v::.) " 1- hvdrokPV-^. - IT^ tvlaTiino- QtanhvdgoIilpirid.
■<:.><...>" ■• . """ " ■'.. 72 g/(0,15 mol) s av ( lon i trinn h ej&olfviy*.£orbindeloé i i;44.iifcer'." /Atanol og 5"g 5&risT vÆiafiiiaa-^ 'åtaoejÆsæar cg 66C, ' Sfter' rtvfclwh'.:.>fc\hy3^ k&t&ly&ratoron, t>gisrøtanol^n -v" ^rafcillosæs." Yte/ c. ^rystailinoka ' raaltfuvni atr^es med acetonit^i"'. rtg-uvsugsG. utbyttes 69 g'.* 95,^. 1 r v £ot tøoreiirTo.' :.' Smaltepunkt: ■. 113°C £2c sfcanol). * ■
• Voi frpnigåhgBEiåtQn' L-' :?;'.^') cvonsfe-Aoncta'^?';r:o^3Sl;Erombtillos £r» ££lg-■■ Q^ido forbindelsens....'
??orbindelBer ;imed gQir-^.''. A te av Ir-y-irra^o Kidsinat
l-( m- stéarylbksvfanvlS -^V^vrlrokBy "2-H-^tvlayiino-otanhvdroklorrid.' ■
A) m»stearvl6kov^ i>- W^ tylQaiÆO' <x! Ot6j:oaon»
22 g m^ydroksy-o>* (53^tyl ^-benzyl-ani.:o) -acot<p>fenonhydroklorid
() ,.065$. mol) bppløoos'£ 157 ml 1 n natronlut, og under omrøring
vad 20 C /tilsettes dr&psvis.22 g (0,0725 mol) stoarylklprid. after'- 20 minutter .opptas.acylér{ngsproduktet;± eter, og derefter .
rystes:dehiorganiske fase først rød 1 n.nafcrbnlut bg dereftér ..-med vann. Den tørrede ct.^rfaDo iimdc^osusYpg residuet hydrogen-aros^mad .390 .ml S6^-ig rr.Jtanol, soa inneholder den beregnede'vasng-de\hydrogenklorid, lø. a?, ;jalle^iua-kloi:;i.d "og 1 g kull under trykk vdd;60°C. bebenjsylorinc;;ia ar'avclutfcev.©£t<sr 5.minutter,* og hydro-gsneringen stander. ■ Katnlyoiitoron av<3t>.g;is.i.varm tilstand, og xxari^ Lt^ B^^ ^^ o^ Xl- y^^& a don ønskes forbindelse ved avkjøl- "" ing,.."' ilåter' *avsugtt5.nc,,.J;^' vrakes kry£iteI?.-'.%io ' ;oad' acotoriitril,: .■ ,. ■'' VK&yttø:- 22 -g" * -SO^ST.' riv det-"teoretisk?/. V-- -:' '. ftcii^sgnuftt-t 195°^ (ov<*,->2y8tåiXioesjca- -Crn etanol).
■£) IM CT^ téarvlokoyforåy 7.) - -1 • -^T/jlrr glt sv-; * ::?- - atylamino - etanhvdrofclo. rid.
....- ■<.>.<.>Vett .katalytiskhy&rogsivsring av 19 g t0,0395 mbl) av deia i,fcr.inn ... A ■ .^ifchplcjte^if.p^rbihdslscs i 400ral asafcahol i. ifcaryar - ov .0-/5-g pia^ista'*-olsréyd ved.nbrmaitsyklo oi?^0°C, feir «nr^' .g 96,5# av'det t,ep- . r^hÅakp^.Bv slu£t&ro£t-røfi tr^Ifeeov^t' 113°C (oakryétåll.invo-jon Ssr. ptaabl)
"mslbg- ;fréfnbtilloo' l --.viyrylokoyffrjiH-./■.:.) • •i*;hydroks'y-2-S'~3t^l-. r^isrø^t^n-hydroklu:.*;!^. wja£$'teptuik^i' 139 v .(6v--?:**'/c.cfr.llic3ao'io3i ><:>rr.- icoprepanol).. ■' - V :"■ ■."*■» ■ » .... ■ ■ *..■'..
1 - ( nt- rstéarvioksyf.- a^ ivli - fry^ roksv"?, v& • '^'^^ ivvgini^ etan- Sivdroklprici!..'
30, 55 ' g; JtfO, 1 mol) in-hyÅroksy-tjr(K-eii^.- &-bangy1 -amino) -aeetpranon-åydrokibrid, oppløst i 250 ml 1 n nafcroalufc, omsattes ved rora--, temperatur'råsd 33";5 r; (-r>,ll mol) nte«:ty^kl.prid til m-stearyloksy-, c^(K^tyl-lff-bahByl-0'vli.-:o) -acetofenon-W^rofclorid. Bfter!20 minutter" f bre tas. utetr ing, og døn .esganisko. fase" rystes- med X »■ natroniu£ pg dorerte:-:'jrød vann. iJtiirfaaen tørres med hatriiAråsul-fat, og oppløsningBiaid^Glet avdeotilla^;ic.. Residuet' oppløses i G00, ml metanol,YiøytrF»*-'loaros msd. notøsioliok saltsyre og under-kastes .hydsrogénering oammøn mod Slanoy-Cii?il;el.. Hydrogeneringdn sK;.\ ox under, -trykfe. og .vad<:>-€0°C. Hydroconopptagelson svarer,il ; 2 ubl /ekvivalenter hyc!rsgen. 2fter frarjkiilelee av katalysatoren
avdeetiileras metanolen i vakuum, og frr. residuet isoleres, den _ øswikede forbindelse...... ':• "; Ptbytté -35. g. 72.5?S r\v c?et teoretiske.... t»p.3ltapunkts 113°C (c.^ystailioaojon f.ira etanol).'
Eksempel. 7 ■■■_.*.;'.<1>ti" . l^ rm- f n- nekBvlkarbonvlcc^ av) - fenvl ' 1 ~ l~ Iwc tr:okBv-- 2- l! ?-^ tvl-^ mlno-- etan--Iwdrbkiprid.^
<f>til.en oppløsning cv 2,*>.V g (0,Ol mol) iMn-hekoylkarbohyloksy)
.<o»^/^tylamino;yacetoisasi.;:.i.. ECl.i SO ml -jstanol tilføres under, jom-raring ved o :til .- écC 0.5 g natriunborliydrid. Sfter 5<:>:'minutter
'iias&Btilles pH.på 5*_-5 ir.addik, og .nbfcasiolen."avdastiller3o i
vÆuum; Residuet epplcH/iu i vann: og crjøros cvakt alkalisk vad til-- .. uatning av; arambhiuifi^yili/cilxyd. Den frigj:,rto base '.av • endof orhind-plncåft opptas, i etylac. tørros riir.d n^tariuiasulfat og inndavæas.Ss:ca residuet i etylfia.si.r^-. tttkryatalli:jor.:j.*u hydrokloridet av for-Mwdalson-iaed;'eterisk ^:'.\Uavre... Unyttes 2,7Å';'g rv det teoråtisk-i.-E^lfcepunkt"i 120°9 (o-■', .■..-..vTJtalliiao^on étylacetati).
• *. ■ ■ - . ■'..-*.■■'
Claims (2)
1. Arialogifremgangsmåte for fremstilling av terapeutisk aktive l-(m-acyloksyfenyl) ' l-hydroksy-2-5!?-alkylaniino-etaner med den generelle formels
hvor betyr en alkylrest mad 3 til 19 karbonatomer, og R2 betyr metyl eller etyl, i form av racemater eller de rene optisk aktive former,- og syreaddisjonssalter derav, karakterisert ved at et acetofenon med formelen:
hvor R, °9 R2 er som oven^or angitt, dg R betyr hydrogen eller en eventuelt substituert bensylrest, reduseres,
en N-benzylrest som eventuelt er tilstede i reduksjonsproduktet, av-spaltes,
racemater med formel I spaltes eventuelt i.de optiske antipoder, og/eller, primaert erholdte syreaddisjonssalter overføres til frie baser eller salter med andre syrer, eller primært erholdte, baser overføres til ønskede syreaddisjonssalter.
2. Fremgangsmåte som angitt i krav 1, karakterisert ved at det anvendes et utgangsmateriale med formel II hvor R^ betyr heptadekyl,•og R2 betyr etyl.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19732341876 DE2341876A1 (de) | 1973-08-18 | 1973-08-18 | Neue 1-(m-acyloxyphenyl)-1-hydroxy- 2-n-alkylamino-aethane, deren saeureadditionssalze, diese enthaltende arzneimittel, sowie verfahren zu ihrer herstellung |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO742946L true NO742946L (no) | 1975-03-17 |
Family
ID=5890134
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO742946A NO742946L (no) | 1973-08-18 | 1974-08-16 |
Country Status (21)
| Country | Link |
|---|---|
| JP (1) | JPS5049241A (no) |
| AT (1) | AT340398B (no) |
| BE (1) | BE818949A (no) |
| BG (1) | BG24406A3 (no) |
| CH (1) | CH603549A5 (no) |
| CS (1) | CS167211B2 (no) |
| DD (1) | DD115489A5 (no) |
| DE (1) | DE2341876A1 (no) |
| DK (1) | DK135942C (no) |
| ES (1) | ES429178A1 (no) |
| FI (1) | FI231674A (no) |
| FR (1) | FR2240727B1 (no) |
| GB (1) | GB1468079A (no) |
| HU (1) | HU168905B (no) |
| IL (1) | IL45482A0 (no) |
| NL (1) | NL7410988A (no) |
| NO (1) | NO742946L (no) |
| PL (1) | PL95296B1 (no) |
| SE (1) | SE7410492L (no) |
| SU (1) | SU505351A3 (no) |
| ZA (1) | ZA745267B (no) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1492361A (en) * | 1975-02-10 | 1977-11-16 | Interx Research Corp | Optically active m-acyloxy-alpha(methylamino)methyl)-benzyl alcohols the pharmaceutically acceptable acid addition salts thereof and synthesis of same |
| DE2933005C2 (de) * | 1979-08-14 | 1983-01-13 | Klinge Pharma GmbH, 8000 München | 1-(3-Acyloxyphenyl)-2-aminoethanole, deren Säureadditionssalze, diese enthaltende Arzneimittel, sowie Verfahren zu ihrer Herstellung |
| CA3001981A1 (en) * | 2014-10-14 | 2016-04-21 | Sculpt B.V. | Body sculpting |
-
1973
- 1973-08-18 DE DE19732341876 patent/DE2341876A1/de active Pending
-
1974
- 1974-07-31 CS CS5457A patent/CS167211B2/cs unknown
- 1974-08-02 FI FI2316/74A patent/FI231674A/fi unknown
- 1974-08-08 AT AT651174A patent/AT340398B/de not_active IP Right Cessation
- 1974-08-12 ES ES429178A patent/ES429178A1/es not_active Expired
- 1974-08-14 FR FR7428296A patent/FR2240727B1/fr not_active Expired
- 1974-08-15 JP JP49093795A patent/JPS5049241A/ja active Pending
- 1974-08-15 SU SU2054091A patent/SU505351A3/ru active
- 1974-08-16 CH CH1118974A patent/CH603549A5/xx not_active IP Right Cessation
- 1974-08-16 SE SE7410492A patent/SE7410492L/xx unknown
- 1974-08-16 GB GB3622974A patent/GB1468079A/en not_active Expired
- 1974-08-16 HU HUBO1515A patent/HU168905B/hu unknown
- 1974-08-16 DD DD180548A patent/DD115489A5/xx unknown
- 1974-08-16 IL IL45482A patent/IL45482A0/xx unknown
- 1974-08-16 DK DK439774A patent/DK135942C/da active
- 1974-08-16 BG BG7400027509A patent/BG24406A3/xx unknown
- 1974-08-16 BE BE147698A patent/BE818949A/xx unknown
- 1974-08-16 ZA ZA00745267A patent/ZA745267B/xx unknown
- 1974-08-16 NL NL7410988A patent/NL7410988A/xx not_active Application Discontinuation
- 1974-08-16 NO NO742946A patent/NO742946L/no unknown
- 1974-08-17 PL PL1974173537A patent/PL95296B1/pl unknown
Also Published As
| Publication number | Publication date |
|---|---|
| FR2240727A1 (no) | 1975-03-14 |
| JPS5049241A (no) | 1975-05-01 |
| ATA651174A (de) | 1977-04-15 |
| CS167211B2 (no) | 1976-04-29 |
| AT340398B (de) | 1977-12-12 |
| FR2240727B1 (no) | 1977-11-04 |
| DK439774A (no) | 1975-04-28 |
| HU168905B (no) | 1976-08-28 |
| PL95296B1 (pl) | 1977-10-31 |
| FI231674A (no) | 1975-02-19 |
| SU505351A3 (ru) | 1976-02-28 |
| BE818949A (fr) | 1975-02-17 |
| ZA745267B (en) | 1976-04-28 |
| AU7242874A (en) | 1976-02-19 |
| SE7410492L (no) | 1975-02-19 |
| IL45482A0 (en) | 1974-11-29 |
| ES429178A1 (es) | 1976-09-01 |
| DK135942C (da) | 1977-12-19 |
| DD115489A5 (no) | 1975-10-05 |
| GB1468079A (en) | 1977-03-23 |
| DK135942B (da) | 1977-07-18 |
| NL7410988A (nl) | 1975-02-20 |
| CH603549A5 (no) | 1978-08-31 |
| BG24406A3 (en) | 1978-02-10 |
| DE2341876A1 (de) | 1975-03-13 |
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