FI62528C - ETT NYTT FOERFARANDE FOER FRAMSTAELLNING AV 1- (3,5-DIHYDROXIPHENYL) -1-HYDROXY-2- (1-METHYL-2- (4-HYDROXYPHENYL) -ETHYL) -AMINOETHANE - Google Patents
ETT NYTT FOERFARANDE FOER FRAMSTAELLNING AV 1- (3,5-DIHYDROXIPHENYL) -1-HYDROXY-2- (1-METHYL-2- (4-HYDROXYPHENYL) -ETHYL) -AMINOETHANE Download PDFInfo
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- FI62528C FI62528C FI750725A FI750725A FI62528C FI 62528 C FI62528 C FI 62528C FI 750725 A FI750725 A FI 750725A FI 750725 A FI750725 A FI 750725A FI 62528 C FI62528 C FI 62528C
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- ethyl
- hydroxy
- hydroxyphenyl
- methyl
- aminoethane
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/34—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
- C07C229/36—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings with at least one amino group and one carboxyl group bound to the same carbon atom of the carbon skeleton
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
- C07C215/46—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C215/56—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains further substituted by hydroxy groups
- C07C215/58—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains further substituted by hydroxy groups with hydroxy groups and the six-membered aromatic ring, or the condensed ring system containing that ring, bound to the same carbon atom of the carbon chain
- C07C215/60—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains further substituted by hydroxy groups with hydroxy groups and the six-membered aromatic ring, or the condensed ring system containing that ring, bound to the same carbon atom of the carbon chain the chain having two carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
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- 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
ral ηη KUULUTUSjULKAISU /αγλλ vgr» m ου utläggningsskrift 6^528 C Patentti myönnetty 10 Cl 1933 <jr>Jv§l ^ Patent .7.e«clelat ^ ^ (51) Kv.lk3/lnt.CI.3 C 07 C 91/34· 750725 SUOMI-FINLAND (*) PtMfittlKakamut — PttanmmBkflJni (22) H*k#ml*p»lvt — AittOknlnpdaf 13·03*75 (23) Alkuplivt—Glfclghttsdai 13·03·75 (41) Tullut lulklMkil — Bllvlt offuKlIg 20.09*75ral ηη ANNOUNCEMENT / αγλλ vgr »m ου utläggningsskrift 6 ^ 528 C Patent granted 10 Cl 1933 <jr> Jv§l ^ Patent .7.e« clelat ^ ^ (51) Kv.lk3 / lnt.CI.3 C 07 C 91/34 · 750725 SUOMI-FINLAND (*) PtMfittlKakamut - PttanmmBkflJni (22) H * k # ml * p »lvt - AittOknlnpdaf 13 · 03 * 75 (23) Alkuplivt — Glfclghttsdai 13 · 03 · 75 (41) Tullut lulklkil Bllvlt offuKlIg 20.09 * 75
Htanttl. ]a r.klrt«4h«mtui NihttvilOp™ f. kuuL|ulk.lWn pvm. - 30.09.82Htanttl. ] a r.klrt «4h« mtui NihttvilOp ™ f. moonL | - 30.09.82
Patent· och ragistarstyrelMn ' ' Ansekan uttagd och uti.*krift*n pubikund (32)(33)(31) Pyydttty «uolkuui —Bugtri prterttat 19-03-71*Patent · och ragistarstyrelMn '' Ansekan uttagd och uti. * Krift * n pubikund (32) (33) (31) Pyydttty «uolkuui —Bugtri prterttat 19-03-71 *
Saksan Liittotasavalta-Förbundsrepubliken Tyskland(DE) P 21+13102.0 (71) C. H. Boehringer Sohn, Ingelheim am Rhein, Saksan Liittotasavalta-Förbundsrepubliken Tyskland(DE) (72) Anton Mentrup, Ingelheim am Rhein, Kurt Schromm, Ingelheim am Rhein, Ernst-Otto Renth, Ingelheim am Rhein, Saksan Liittotasavalta-Förbundsrepubliken Tyskland(DE) (7t) Leitzinger Oy (5M Uusi menetelmä l-(3,5“äihydroksifenyyli)-l-hydroksi-2-£L-metyyli-2--(^-hydroksifenyyli)-etyyli_7-aminoetaanin valmistamiseksi - Ett nytt förfarande för framställning av l-(3,5-dihydroxifenyl)-l-hydroxi-2--ä -metyl-2-(U-hydroxifenyl)-etyl7-aminoetanFederal Republic of Germany Förbundsrepubliken Tyskland (DE) P 21 + 13102.0 (71) CH Boehringer Sohn, Ingelheim am Rhein, Federal Republic of Germany Förbundsrepubliken Tyskland (DE) (72) Anton Mentrup, Ingelheim am Rhein, Kurt Schromm, Ergelst am Rhein Otto Renth, Ingelheim am Rhein, Federal Republic of Germany-Förbundsrepubliken Tyskland (DE) (7t) Leitzinger Oy (5M New method 1- (3,5 “dihydroxyphenyl) -1-hydroxy-2H-methyl-2- -hydroxyphenyl) -ethyl-7-aminoethane - For the preparation of 1- (3,5-dihydroxyphenyl) -1-hydroxy-2-α-methyl-2- (U-hydroxyphenyl) -ethyl-7-aminoethane
Keksinnön kohteena on uusi menetelmä 1-(3,5-dihydroksifenyyli)-1-hydroksi-2-2l-metyyli-2-(4-hydroksifenyyli)-etyyliT-aminoetaanin, jolla on kaavaThe present invention relates to a new process for the preparation of 1- (3,5-dihydroxyphenyl) -1-hydroxy-2-2-methyl-2- (4-hydroxyphenyl) ethyl] -aminoethane of the formula
OHOH
1_ ^H31_ ^ H3
\ 'S— CH(OH)-CH9-NH-CH-CH, —V 'K— OH\ 'S - CH (OH) -CH9-NH-CH-CH, -V'K-OH
(i)(I)
OHOH
mahdollisesti diastereomeereinä, ja vastaavien happoadditiosuolojen valmistamiseksi.optionally as diastereomers, and to prepare the corresponding acid addition salts.
Uusi menetelmä voidaan esittää seuraavalla reaktiokaaviolla: 2 : 2 8The new method can be represented by the following reaction scheme: 2: 2 8
Keksinnön mukaiselle menetelmälle kaavan I mukaisen bronkolvyttisen ja tokolyyttisen yhdisteen valmistamiseksi on tunnusomaista se, että pelkistetään liuottimessa natriumboorihydridillä kaavan II mukainen yhdiste OR, l_L “3 O y—co-ch-n-ch-ch2—& y—or2 di) OR^ jossa tarkoittaa bentsyyliryhmää, joka voi olla substituoitu alemmalla alkyylillä tai alkoksilla ja R2 tarkoittaa vetyä tai bentsyyliryhmää, joka voi olla substituoitu alemmalla alkvylillä tai alkoksilla, ja saadusta kaavan III mukaisesta yhdisteestä lohkaistaan suojaryhmät tavanomaisilla hydrogenolyyttisillä menetelmillä, haluttaessa suoritetaan erottaminen diastereomeerisiin anti-podipareihin joko ennen suojaryhmien lohkaisua tai sen jälkeen ja haluttaessa valmistetaan halutut happoadditiosuolat tai vapaat emäkset tavanomaisin menetelmin.The process according to the invention for the preparation of a broncholytic and tocolytic compound of the formula I is characterized in that the compound of the formula II is reduced in a solvent with sodium borohydride OR, l-L denotes a benzyl group which may be substituted by lower alkyl or alkoxy and R 2 represents hydrogen or a benzyl group which may be substituted by lower alkyl or alkoxy, and the resulting compound of formula III is deprotected by conventional hydrogenolytic methods to give or thereafter and, if desired, preparing the desired acid addition salts or free bases by conventional methods.
Ryhmien R^ ja Rj laadulla on reaktion kulkuun vähäinen merkitys. Niiden ei tule kuitenkaan sisältää sellaisia substituentteja, jotka reaktion olosuhteissa muuttuvat voimakkaasti. Lähtöaineissa on tarkoituksenmukaista käyttää mahdollisimman yksinkertaisia ryhmiä ja R2. Siten käytetään parhaiten sellaisia lähtöaineita, joissa R^ tarkoittaa bentsyyliä ja R2 vetyä tai bentsyyliä.The quality of the groups R 1 and R 2 is of minor importance to the course of the reaction. However, they should not contain substituents which change strongly under the reaction conditions. It is appropriate to use as simple groups and R2 as possible in the starting materials. Thus, starting materials in which R 1 represents benzyl and R 2 represents hydrogen or benzyl are best used.
Pelkistäminen suoritetaan liuottimessa, joka sopii natriumboori-hydridille tapahtuvaan pelkistykseen, esimerkiksi alemmassa alko- 3 62528 holissa (metanoli, etanoli, propanoli), dioksaanissa, tetrahydro-furaanissa, mahdollisesti toistensa seoksessa tai seoksessa veden kanssa, lämpötiloissa noin 0°C ja huoneen lämpötilan välillä, haluttaessa myös alhaisemmissa tai korkeammissa lämpötiloissa.The reduction is carried out in a solvent suitable for reduction with sodium borohydride, for example in lower alcohol (methanol, ethanol, propanol), dioxane, tetrahydrofuran, optionally in a mixture or mixture with water, at temperatures between about 0 ° C and room temperature. , also at lower or higher temperatures if desired.
Hydrogenolyyttinen suojaryhmien lohkaiseminen tapahtuu sinänsä tunnetuilla menetelmillä. Katalyyteiksi sopivat siten esimerkiksi platina, palladium, Raney-nikkeli, rodium. Liuottimina voidaan käyttää ennen kaikkea metanolia. Lämpötila ja paine voidaan valita laajoissa rajoissa; parhaiten kuitenkin toimitaan huoneen lämpötilassa tai hieman korotetussa lämpötilassa ja paineessa, jotka ovat normaalipaineen ja 10 atm.:n välillä.Hydrogenolytic cleavage of the protecting groups takes place by methods known per se. Suitable catalysts are, for example, platinum, palladium, Raney nickel and rhodium. In particular, methanol can be used as the solvent. Temperature and pressure can be selected over a wide range; however, it is best operated at room temperature or at a slightly elevated temperature and pressure between normal pressure and 10 atm.
Diastereomeeriset antipodiparit saadaan siten, että joko erotetaan pelkistämistuote (yhdiste lii) diastereomeeristen antipodiparien erilaisen liukenevuuden perusteella ja sen jälkeen lohkaistaan suojaryhmät, tai siten, että hajotetaan diastereomeerien I seos, joka on saatu kaavan III mukaiselle yhdisteelle suoritetun suoja-ryhmien lohkaisemisen jälkeen.Diastereomeric antipode pairs are obtained either by separating the reduction product (compound lii) on the basis of the different solubilities of the diastereomeric antipode pairs and then cleaving the protecting groups, or by decomposing the mixture of diastereomers I obtained after deprotection of the compound of formula III.
Happoadditiosuolat valmistetaan saaduista yhdisteistä tavalliseen tapaan. Jos halutaan saada vapaat emäkset, ne voidaan haluttaessa vapauttaa ensin saaduista happoadditiosuoloista tavalliseen tapaan.Acid addition salts are prepared from the obtained compounds in the usual manner. If it is desired to obtain the free bases, they can, if desired, be liberated from the acid addition salts first obtained in the usual manner.
Kaavan II mukaiset lähtöaineet voidaan valmistaa reaktiokaavion / R3 f”3 e y— CO-CH ^ + H2N-CH-CH2—^ ^~*0R2—^ 11 0R1 mukaisesti. R3 tarkoittaa hydroksiryhmää tai mahdollisesti substi-tuoitua alkoksi- tai sykloalkoksiryhmää.The starting materials of the formula II can be prepared according to the reaction scheme / R3 f ”3 e y— CO-CH2 + H2N-CH-CH2- ^ ^ ~ * 0R2— ^ 11 0R1. R3 represents a hydroxy group or an optionally substituted alkoxy or cycloalkoxy group.
Keksinnön mukainen menetelmä on tunnettuihin menetelmiin, joilla vai- 4 62528 mistetaan kaavan I mukaisia yhdisteitä, verrattuna yksinkertaisempi ja antaa paremman saannon. DE-patenttijulkaisusta 1 286 047 tunnetaan menetelmä, jolla kaavan I mukaista yhdistettä valmistetaan 7 reaktiovaiheen kautta kokonaissaannolla 6,72 %. Samaa lähtöainetta käyttäen saadaan keksinnön 5:llä reaktiovaiheella saannoksi 22 %.The process according to the invention is simpler and gives a better yield compared to the known processes for attenuating the compounds of the formula I. DE-A-1 286 047 discloses a process for the preparation of a compound of the formula I via 7 reaction steps in a total yield of 6.72%. Using the same starting material, the reaction step 5 of the invention gives a yield of 22%.
Seuraava esimerkki kuvaa keksinnön mukaista menetelmää lähemmin: Esimerkki a) 3,5-dibentsyylloksifenyyliglyoksaali-etyyliasetaali 332 g (1 mooli) 3,5-dibentsyylioksiasetofenonia ja 105,2 g (0,95 moolia) seleenidioksidia keitetään refluksoiden seoksessa, jossa on 1200 ml dioksaania ja 50 ml vettä, kunnes seleeniä on saostunut noin 72 g. Aktiivihiilellä puhdistettu dioksaaniliuos haihdutetaan ja jäännös liuotetaan 1 litraan kuumaa 90-prosenttista etanolia. Liuokseen lisätään ymppäyskiteitä. Alkanut kiteytyminen saatetaan loppun 4 tunnin kuluttua jäähdyttämällä. Erotettu tuote kiteytetään uudelleen 10-kertaisesta määrästä etanolia, jolloin saadaan 317 g (80,9 % teoreettisesta) 3,5-dibentsyylioksifenyyliglyoksaali-etyyliasetaalia.The following example further illustrates the process according to the invention: Example a) 3,5-Dibenzyloxyphenylglyoxal-ethyl acetal 332 g (1 mol) of 3,5-dibenzyloxyacetophenone and 105.2 g (0.95 mol) of selenium dioxide are refluxed in a mixture of 1200 ml of dioxane. and 50 ml of water until about 72 g of selenium has precipitated. The dioxane solution purified on activated carbon is evaporated and the residue is dissolved in 1 liter of hot 90% ethanol. Seed crystals are added to the solution. The onset of crystallization is completed after 4 hours by cooling. The separated product is recrystallized from 10 times the amount of ethanol to give 317 g (80.9% of theory) of 3,5-dibenzyloxyphenylglyoxal-ethyl acetal.
b) 1-(3,5-dibentsyylioksifenyyli)-l-hydroksi-2-/l-metyyli-2-(4- hydroksi-fenyyli) -etyyljL7-aminoetaani_ 107,8 g (0,275 moolia) 3,5-dibentsyylioksifenyyliglyoksaali-etyyli-asetaalia ja 37,75 g (0,25 moolia) 1-(4-hydroksifenyyli)-propyyli-2-amiinia liuotetaan 1 litraan etanolia 50°C:ssa, annetaan seistä 3 tuntia huoneen lämpötilassa ja suodatetaan aktiivihiilen läpi. 0°C:een jäähdytettyyn liuokseen lisätään pieninä erinä 18 g natriumboorihydridiä. Annetaan seistä yön yli, tehdään happameksi 250 ml:11a 4n suolahappoa jäähdyttäen hyvin ja tislataan alkoholi pois tyhjiössä.b) 1- (3,5-dibenzyloxyphenyl) -1-hydroxy-2- [1-methyl-2- (4-hydroxy-phenyl) -ethyl] -7-aminoethane-107.8 g (0.275 moles) of 3,5-dibenzyloxyphenylglyoxal ethyl acetal and 37.75 g (0.25 mol) of 1- (4-hydroxyphenyl) -propyl-2-amine are dissolved in 1 liter of ethanol at 50 ° C, allowed to stand for 3 hours at room temperature and filtered through activated carbon. 18 g of sodium borohydride are added in small portions to the solution cooled to 0 ° C. Allow to stand overnight, acidify with 250 ml of 4N hydrochloric acid, cooling well and distill off the alcohol in vacuo.
Lisäämällä vettä ja ammoniakkia vapautetaan emäs, joka otetaan etyyliasetaattiin. Etikkahappoesterin tislaamisen jälkeen jää jäljelle 148 g otsikkoyhdistettä III.Addition of water and ammonia liberates the base which is taken up in ethyl acetate. After distilling off the acetic acid ester, 148 g of the title compound III remain.
5 62528 c) Yhdisteen III erottaminen dlastereomeerelhin III a ja III b 36 g maleiinihappoa, joka on liuotettu 300 ml:aan etyyliasetaattia, lisätään 148 g:aan yhdistettä III 1,5 litrassa etyyliasetaattia. Diastereomeerin III a maleinaatti kiteytyy 55 g saannolla. Yhdisteen III a maleinaatin sulamispiste on 136°C (asetonitriilistä). Emäliuos käsitellään 2n ammoniakkiliuoksella ja sen jälkeen vedellä. Erotettu etyyliasetaattifaasi kuivataan ja tislataan hyvin. 500 ml:aan etyyliasetaattia otettu jäännös tehdään happameksi eetteripitoisella suolahapolla pH-arvoon 4,2, jolloin saadaan diastereomeerin III b hydro-kloridi. Kiteytetään uudelleen 15-kertäisestä asetonitriilimäärästä, jolloin saadaan 47,5 g isomeeriä III b hydrokloridina, sulamispiste 176°C. Jatkokäsittelemällä emäliuosta voidaan diastereomeerien III a ja III b saantoa vielä parantaa.5 62528 c) Separation of compound III Dlastereomers IIIa and IIIb 36 g of maleic acid dissolved in 300 ml of ethyl acetate are added to 148 g of compound III in 1.5 liters of ethyl acetate. The maleate of diastereomer III a crystallizes in a yield of 55 g. The maleinate of Compound IIIa has a melting point of 136 ° C (from acetonitrile). The mother liquor is treated with 2N ammonia solution and then with water. The separated ethyl acetate phase is dried and distilled well. The residue taken up in 500 ml of ethyl acetate is acidified to pH 4.2 with ethereal hydrochloric acid to give the hydrochloride of diastereomer IIIb. Recrystallize from 15 times the amount of acetonitrile to give 47.5 g of isomer III b as the hydrochloride, m.p. 176 ° C. By further treatment of the mother liquor, the yield of diastereomers IIIa and IIIb can be further improved.
d) 1-(3,5-dihydroksifenyyli)-l-hydroksi-2-/l-metyyli-2-(4-hydroksi- fenyyli)-etyyli^-aminoetaani-hydrobromidi puhtaina diastereomee-reinä_ 9 g III-a-maleinaattia liuotetaan veteen ja lisätään 15 ml väkevää ammoniakkia. Kaksi kertaa etyyliasetaatin kanssa ravisteltu liuos kuivataan ja tislataan. Jäännös muunnetaan hydrobromidiksi III asetoni triilissä 48-prosenttisella bromivetyhapolla. Saanto on 8,35 g (98,5 %), sulamispiste on 155°C.d) 1- (3,5-Dihydroxyphenyl) -1-hydroxy-2- [1-methyl-2- (4-hydroxyphenyl) ethyl] aminoethane hydrobromide as pure diastereomers 9 g of III-α-maleinate dissolve in water and add 15 ml of concentrated ammonia. The solution, shaken twice with ethyl acetate, is dried and distilled. The residue is converted to the hydrobromide III in acetone tril with 48% hydrobromic acid. Yield 8.35 g (98.5%), melting point 155 ° C.
Hydrobromidi liuotetaan 120 ml:aan metanolia ja hydrataan Pd/C:llä huoneen lämpötilassa ja normaalipaineessa, kunnes vetyä on kulunut teoreettinen määrä. Saadaan 5,3 g yhdistettä I a hydrobromidina, sulamispiste 230°C.The hydrobromide is dissolved in 120 ml of methanol and hydrogenated with Pd / C at room temperature and normal pressure until the theoretical amount of hydrogen has been consumed. 5.3 g of compound Ia are obtained in the form of hydrobromide, m.p. 230 ° C.
Isomeerisen III b-hydrokloridin hydrauksen kanssa analogisesti saadaan isomeeriä I b hydrokloridina saannolla 96 %, sulamispiste 155-188°C.In analogy to the hydrogenation of isomeric III b-hydrochloride, isomer I b as hydrochloride is obtained in a yield of 96%, melting point 155-188 ° C.
e) 1- (3,5-dihydroksifenyyli)-l-hydroksi-2-/i-metyyli-2-(4-hydroksi-fenyyli)-etyyli/-aminoetaanl-hydrobromldl diastereomeerlseoksena 14,8 g yhdistettä III liuotetaan 150 ml:aan metanolia ja muunnetaan hydrobromidiksi lisäämällä bromivetyhappoa. Lisätään palladium/hiiltä ja hydrataan, kunnes vetyä on kulunut teoreettinen määrä. Metanolin tislaamisen jälkeen diastereomeeriseos I a ja I b eristetään lisäämällä 25 ml vettä ja 25 ml väkevää bromivetyhappoa, saanto 95 %$ sulamispis te 191-199°C.e) As a diastereomeric mixture of 1- (3,5-dihydroxyphenyl) -1-hydroxy-2- (i-methyl-2- (4-hydroxyphenyl) ethyl) aminoamino] hydrobromide, 14.8 g of compound III are dissolved in 150 ml of: methanol and converted to hydrobromide by the addition of hydrobromic acid. Add palladium / carbon and hydrogenate until the theoretical amount of hydrogen is consumed. After distilling off the methanol, the diastereomeric mixture Ia and Ib is isolated by adding 25 ml of water and 25 ml of concentrated hydrobromic acid, yield 95% melting point 191-199 ° C.
6 62528 f) Diastereomeerin I a erottaminen dlastereomeeriseoksesta6 62528 f) Separation of diastereomer Ia from the mixture of diastereomers
Diastereomeerien I a ja I b eristämiseksi keitetään 18 g kohdan e) mukaisesti saatua seosta ja 55 ml isopropanolia, ja jäännös saostetaan metanoli/kloroformista. Saadaan 6,5 g diastereomeeriä I a, sulamispiste 227-230°C.To isolate diastereomers Ia and Ib, 18 g of the mixture obtained in e) and 55 ml of isopropanol are boiled and the residue is precipitated from methanol / chloroform. 6.5 g of diastereomer Ia are obtained, melting point 227-230 ° C.
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2413102 | 1974-03-19 | ||
| DE2413102A DE2413102C3 (en) | 1974-03-19 | 1974-03-19 | Process for the production of l- (3,5-dihydroxyphenyl) -t-hydroxy-2-square brackets on 1-methyl-2- (4-hydroxyphenyl) -ethyl] -aminoethane |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI750725A FI750725A (en) | 1975-09-20 |
| FI62528B FI62528B (en) | 1982-09-30 |
| FI62528C true FI62528C (en) | 1983-01-10 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI750725A FI62528C (en) | 1974-03-19 | 1975-03-13 | ETT NYTT FOERFARANDE FOER FRAMSTAELLNING AV 1- (3,5-DIHYDROXIPHENYL) -1-HYDROXY-2- (1-METHYL-2- (4-HYDROXYPHENYL) -ETHYL) -AMINOETHANE |
Country Status (13)
| Country | Link |
|---|---|
| JP (1) | JPS50131936A (en) |
| AT (1) | AT339884B (en) |
| BG (1) | BG27075A3 (en) |
| CH (1) | CH607993A5 (en) |
| CS (1) | CS181290B2 (en) |
| DE (1) | DE2413102C3 (en) |
| DK (1) | DK136184C (en) |
| ES (1) | ES435498A1 (en) |
| FI (1) | FI62528C (en) |
| HU (1) | HU169834B (en) |
| NO (1) | NO140378C (en) |
| SE (1) | SE423091B (en) |
| YU (1) | YU37111B (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JPS5256217A (en) * | 1975-11-01 | 1977-05-09 | Nissan Motor Co Ltd | Exhaust purifying system for internal combustion engine |
| CA1145766A (en) * | 1978-07-03 | 1983-05-03 | Jack Mills | Optically active phenethanolamines and method for increasing cardiac contractility |
| CH653322A5 (en) * | 1982-12-01 | 1985-12-31 | Siegfried Ag | METHOD FOR PRODUCING PHENYLETHANOLAMINES. |
| WO2014108449A1 (en) | 2013-01-08 | 2014-07-17 | Atrogi Ab | A screening method, a kit, a method of treatment and a compound for use in a method of treatment |
| GB201714745D0 (en) | 2017-09-13 | 2017-10-25 | Atrogi Ab | New compounds and uses |
| GB201714734D0 (en) | 2017-09-13 | 2017-10-25 | Atrogi Ab | New compounds and uses |
| GB201714740D0 (en) | 2017-09-13 | 2017-10-25 | Atrogi Ab | New compounds and uses |
| GB201714736D0 (en) | 2017-09-13 | 2017-10-25 | Atrogi Ab | New compounds and uses |
| GB202205895D0 (en) | 2022-04-22 | 2022-06-08 | Atrogi Ab | New medical uses |
-
1974
- 1974-03-19 DE DE2413102A patent/DE2413102C3/en not_active Expired
-
1975
- 1975-02-28 AT AT153975A patent/AT339884B/en not_active IP Right Cessation
- 1975-03-11 ES ES435498A patent/ES435498A1/en not_active Expired
- 1975-03-13 FI FI750725A patent/FI62528C/en not_active IP Right Cessation
- 1975-03-14 CS CS7500001749A patent/CS181290B2/en unknown
- 1975-03-14 CH CH326975A patent/CH607993A5/en not_active IP Right Cessation
- 1975-03-17 BG BG7529327A patent/BG27075A3/xx unknown
- 1975-03-17 HU HUBO1540A patent/HU169834B/hu unknown
- 1975-03-18 DK DK110175A patent/DK136184C/en active
- 1975-03-18 YU YU0673/75A patent/YU37111B/en unknown
- 1975-03-18 JP JP50032839A patent/JPS50131936A/ja active Pending
- 1975-03-18 SE SE7503083A patent/SE423091B/en unknown
- 1975-03-18 NO NO750922A patent/NO140378C/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ES435498A1 (en) | 1976-12-01 |
| DK136184C (en) | 1978-03-20 |
| FI750725A (en) | 1975-09-20 |
| ATA153975A (en) | 1977-03-15 |
| SE7503083L (en) | 1975-09-22 |
| BG27075A3 (en) | 1979-08-15 |
| AT339884B (en) | 1977-11-10 |
| DE2413102C3 (en) | 1980-09-11 |
| NO750922L (en) | 1975-09-22 |
| YU67375A (en) | 1983-04-27 |
| JPS50131936A (en) | 1975-10-18 |
| SE423091B (en) | 1982-04-13 |
| NO140378C (en) | 1979-08-22 |
| DK110175A (en) | 1975-09-20 |
| DE2413102A1 (en) | 1975-10-09 |
| CH607993A5 (en) | 1978-12-15 |
| DK136184B (en) | 1977-08-29 |
| YU37111B (en) | 1984-08-31 |
| NO140378B (en) | 1979-05-14 |
| HU169834B (en) | 1977-02-28 |
| DE2413102B2 (en) | 1980-01-17 |
| CS181290B2 (en) | 1978-03-31 |
| FI62528B (en) | 1982-09-30 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed |
Owner name: C.H. BOEHRINGER SOHN |