HU186649B - Process for producing 1-isopropyl-amino-3-square bracket-4-bracket-2-2-methoxy-ethyl-bracket closed-phenoxy-square bracket closed-2-propanol /metoprolol/ - Google Patents
Process for producing 1-isopropyl-amino-3-square bracket-4-bracket-2-2-methoxy-ethyl-bracket closed-phenoxy-square bracket closed-2-propanol /metoprolol/ Download PDFInfo
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- HU186649B HU186649B HU824069A HU406982A HU186649B HU 186649 B HU186649 B HU 186649B HU 824069 A HU824069 A HU 824069A HU 406982 A HU406982 A HU 406982A HU 186649 B HU186649 B HU 186649B
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- Hungary
- Prior art keywords
- bracket
- phenoxy
- propanol
- closed
- methoxy
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 15
- IUBSYMUCCVWXPE-UHFFFAOYSA-N metoprolol Chemical compound COCCC1=CC=C(OCC(O)CNC(C)C)C=C1 IUBSYMUCCVWXPE-UHFFFAOYSA-N 0.000 title claims abstract description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N 2-propanol Substances CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 title abstract description 7
- 229960002237 metoprolol Drugs 0.000 title abstract description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims abstract description 12
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims abstract description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims abstract description 9
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 claims abstract description 7
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 5
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 3
- MELFVOGWPJFQBB-UHFFFAOYSA-N 3-[4-(2-methoxyethyl)phenoxy]propane-1,2-diol Chemical compound COCCC1=CC=C(OCC(O)CO)C=C1 MELFVOGWPJFQBB-UHFFFAOYSA-N 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 claims description 2
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 claims 1
- DNIAPMSPPWPWGF-UHFFFAOYSA-N monopropylene glycol Natural products CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims 1
- 235000013772 propylene glycol Nutrition 0.000 claims 1
- 125000005270 trialkylamine group Chemical group 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- CTKINSOISVBQLD-UHFFFAOYSA-N Glycidol Chemical compound OCC1CO1 CTKINSOISVBQLD-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical class CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
- FAYGEALAEQKPDI-UHFFFAOYSA-N 4-(2-methoxyethyl)phenol Chemical compound COCCC1=CC=C(O)C=C1 FAYGEALAEQKPDI-UHFFFAOYSA-N 0.000 description 1
- GEIILWZONNWCMO-UHFFFAOYSA-N 4-[[4-(2-methoxyethyl)phenoxy]methyl]-1,3,2-dioxathiolane 2-oxide Chemical compound C1=CC(CCOC)=CC=C1OCC1OS(=O)OC1 GEIILWZONNWCMO-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 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
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/06—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton from hydroxy amines by reactions involving the etherification or esterification of hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C217/04—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C217/28—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having one amino group and at least two singly-bound oxygen atoms, with at least one being part of an etherified hydroxy group, bound to the carbon skeleton, e.g. ethers of polyhydroxy amines
- C07C217/30—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having one amino group and at least two singly-bound oxygen atoms, with at least one being part of an etherified hydroxy group, bound to the carbon skeleton, e.g. ethers of polyhydroxy amines having the oxygen atom of at least one of the etherified hydroxy groups further bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/30—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 doubly-bound oxygen atoms
- C07C233/33—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 doubly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Saccharide Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
A találmány tárgya eljárás az (1) képletű 1-izopropilarnino-3-[4-(2-metoxi-etiI)-fenoxi]-2-propanol (nretoprolol) előállítására. A metoprolol ismert kemoterapeutikum,The present invention relates to a process for the preparation of 1-isopropylarnino-3- [4- (2-methoxyethyl) phenoxy] -2-propanol (nretoprolol). Metoprolol is a known chemotherapeutic agent,
A 354 851 számú svéd szabadalmi leírás több különböző módszert közöl a metoprolol előállítására. Ezek közül a módszerek közül a legjobb az, amelyben a (11) képletű vegyületet izopropil-aminnal reagáltatják. Az eljárás hozama azonban csak mintegy 50%-os. Ez főként a nemkívánatos meliékreakcióknak tulajdonítható, amelyek pl. az izomér 1-propanol-származék képződéséhez vezetnek. A (II) képletű vegyület előállítását is zavarják mellékreakciók.Swedish Patent No. 354,851 discloses several different methods of preparing metoprolol. The best of these methods is one in which the compound of formula (11) is reacted with isopropylamine. However, the yield of the process is only about 50%. This is mainly attributable to unwanted side reactions, which, e.g. leading to the formation of the isomeric 1-propanol derivative. The preparation of the compound of formula II is also hindered by side reactions.
Az 57-2246 számú közrebocsátott japán szabadalmi bejelentés (Chem. Abstr., 97, 5962) ismertet egy eljárást az l-izopropil-amino-3-(2-allil-fenoxi)-2-propanol előállítására, amelyben a (III) képletű vegyületet tionil-kloriddal reagáltatják dietil-éterben piridin jelenlétében és a kapott 4- t(2-allil-fenoxi)-metii]-1,3,2-dioxatiolán-2-oxidot autóklávban, dimetil-formamidos közegben 2 napig izopropil-aminnal főzve az l-izopropil-amino-3-(2-allilfenoxi)-2-propanolt kapják végtermékül.Japanese Patent Application Publication No. 57-2246 (Chem. Abstr., 97, 5962) discloses a process for the preparation of 1-isopropylamino-3- (2-allylphenoxy) -2-propanol, wherein is reacted with thionyl chloride in diethyl ether in the presence of pyridine and the resulting 4- t (2-allyl-phenoxy) -methyl] -1,3,2-dioxathiolane-2-oxide is autoclaved in isopropylamine in dimethylformamide medium for 2 days. l-isopropylamino-3- (2-allylphenoxy) -2-propanol is obtained.
Arra a felismerésre jutottunk, hogy a metoprololt elő lehet állítani úgy, hogy a (IV) képletű 3-[4-(2-metoxietil)-fenoxi]-l,2-propándiolt diklór-metános közegben tionil-kloriddal, ekvivalens mennyiségű tríalkil-amin jelenlétében az (V) képletű 4-{4-Í2-metoxi-etil)-fenoxijmetil)-I,3,2-dio.xatiolán-2-oxiddá alakítjuk át; ezt a vegyületet azután acetonitrilben izopropil-aminnal reagáltatva kapjuk a metoprololt.It has now been found that metoprolol can be prepared by reacting 3- [4- (2-methoxyethyl) phenoxy] -1,2-propanediol of formula IV with thionyl chloride in dichloromethane in an equivalent amount. in the presence of an amine, converting 4- (4-1,2-methoxyethyl) phenoxymethyl) -1,3,2-dioxoxathiolane-2-oxide of formula (V); this compound is then reacted with isopropylamine in acetonitrile to give metoprolol.
A reakciót előnyösen úgy végezzük, amint azt a találmány szerinti eljárás bemutatására szolgáló példában leírjuk.The reaction is preferably carried out as described in the example to illustrate the process of the invention.
A (IV) képletű vegyületet 4-(2-metoxi-etil)-fenol és glicidol (=2,3-epoxi-l-propanol) báziskatalizált reakciójával állítjuk elő.The compound of formula (IV) is prepared by the base catalyzed reaction of 4- (2-methoxyethyl) phenol and glycidol (= 2,3-epoxy-1-propanol).
A találmány szerinti eljárással a metoprololt jó hozammal lehet előállítani (az átalakítás mintegy 77 %-kal valósítható meg a (ÍV) képletű vegyületre számítva). A kapott termék igen tiszta. Az izomér 1-propanol származékból csak jelentéktelen mennyiség képződik a reakció során.The process of the present invention provides metoprolol in good yield (about 77% conversion to compound of formula (V)). The product obtained is very pure. Only a negligible amount of the isomeric 1-propanol derivative is formed during the reaction.
Az 57-2246 számú közrebocsátott japán bejelentés szerinti eljárás ipari alkalmazásánál hátrány, hogy az első reakciólépésben dietil-étert kell használni, valamint hogy a második lépés megvalósításához szükséges idő igen hosszú. Ezzel szemben a találmány szerinti eljárás ezeket a hátrányokat kiküszöböli és ipari méretekben is könynyen és gazdaságosan megvalósítható.The industrial application of Japanese Patent Application Publication No. 57-2246 has the disadvantage of using diethyl ether in the first reaction step and that the time required for the second step is very long. In contrast, the process of the invention overcomes these drawbacks and is readily and economically feasible on an industrial scale.
PéldaExample
a) 4- {4-\j2-metoxi-etil)-fenoxi\-metil}-1,3,2-dioxatiolán-2-oxid) ( V) képletű köztermék előállítása.'a) Preparation of 4- (4- (2-methoxyethyl) phenoxy-methyl) -1,3,2-dioxathiolane-2-oxide).
22,6 g (0,1 mól) 3-[4-l2-metoxi-fenil)-fenoxi]-l,2propándiolt és 10,1 g (0,1 mól) trietil-amint feloldunk 00 ml diklór-metánban. Ezt az oldatot 10 ml diklór-metánban oldott 7,3 ml tionil-kloriddal elegyítjük 0°C-on. 5 Az elegyet 15 percig kevertetjük 0-5 °C hőmérsékleten, majd 0,1 n sósavval és vízzel mossuk; a szerves fázist nátrium-szulfáttal szárítjuk. Az oldatot vákuumban szárazra bepároljuk. így 25,8 g cím szerinti vegyületet nyerünk 95%-os kitermeléssel. A termék azonosításához 10 a protonrezonancia spektrumból a kémiai eltolódás értékeket közöljük: 2,76 (2Ht), 3,27 (3Hs), 3,50 (2Hs),22.6 g (0.1 mol) of 3- [4-1,2-methoxyphenyl) phenoxy] -1,2-propanediol and 10.1 g (0.1 mol) of triethylamine are dissolved in 00 ml of dichloromethane. This solution was mixed with 7.3 ml of thionyl chloride in 10 ml of dichloromethane at 0 ° C. The mixture was stirred for 15 minutes at 0-5 ° C and then washed with 0.1 N hydrochloric acid and water; the organic phase is dried over sodium sulfate. The solution was evaporated to dryness in vacuo. 25.8 g of the title compound are obtained in 95% yield. The chemical shift values from 10 proton resonance spectra are 2.76 (2Ht), 3.27 (3Hs), 3.50 (2Hs),
3,50 (2Ht), 3,76-4,81 (4Hm), 5,20 (lHqv), 6,66 (2Hd), ',03 (2Hd).3.50 (2Ht), 3.76-4.81 (4Hm), 5.20 (1HHv), 6.66 (2Hd), 1.03 (2Hd).
h) 1 -izopropil-amino-3- (4-( 2-metoxi-etil)-fznoxi ]2-propanol előállításah) Preparation of 1-isopropylamino-3- (4- (2-methoxyethyl) phenoxy] 2-propanol
2,74 g (0,01 mól) az a) példa szerint előállított (V) képletű vegyülethez 7 ml izopropil-amint adva, az elegyet 25 ml acetonitrilben 20 óra hosszat visszafolyatós hűtő alkalmazásával forraljuk. Az oldószereket eltávolítva 25 ml 1 n nátrium-hidroxid oldatot adunk a bepárlási maradékhoz és az így kapott elegyet etil-acetáttal ki25 rázzuk. Az etil-acetátos kivonatot vízzel mossuk, majd szárítjuk. Ezután metanolban oldott ekvivalens mennyiségű borkősavat adunk a maradékhoz. EredményülTo the compound (V) (2.74 g, 0.01 mol) in Example a) was added isopropylamine (7 ml) and the mixture was refluxed in acetonitrile (25 ml) for 20 hours. After removal of the solvents, 25 ml of 1 N sodium hydroxide solution were added to the residue and the resulting mixture was shaken with ethyl acetate. The ethyl acetate extract was washed with water and dried. An equivalent amount of tartaric acid dissolved in methanol was then added to the residue. The result
2,79 g cím szerinti vegyüÍetet kapunk borkősavas só alakjában. Olvadáspont: 134—116 °C, a hozam 81%.2.79 g of the title compound are obtained in the form of the tartaric acid salt. 134-116 ° C, 81% yield.
Claims (4)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FI814053 | 1981-12-17 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HU186649B true HU186649B (en) | 1985-08-28 |
Family
ID=8514961
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU824069A HU186649B (en) | 1981-12-17 | 1982-12-16 | Process for producing 1-isopropyl-amino-3-square bracket-4-bracket-2-2-methoxy-ethyl-bracket closed-phenoxy-square bracket closed-2-propanol /metoprolol/ |
Country Status (9)
| Country | Link |
|---|---|
| JP (2) | JPS58159449A (en) |
| KR (1) | KR840002768A (en) |
| CA (1) | CA1198125A (en) |
| DK (2) | DK156567C (en) |
| HU (1) | HU186649B (en) |
| NO (2) | NO824232L (en) |
| SE (2) | SE452612B (en) |
| SU (1) | SU1170968A3 (en) |
| YU (2) | YU275882A (en) |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS56152461A (en) * | 1980-04-30 | 1981-11-26 | Ota Seiyaku Kk | Preparation of indole derivative |
-
1982
- 1982-12-06 KR KR1019820005450A patent/KR840002768A/en unknown
- 1982-12-07 DK DK542082A patent/DK156567C/en not_active IP Right Cessation
- 1982-12-07 DK DK541982A patent/DK541982A/en not_active Application Discontinuation
- 1982-12-14 YU YU02758/82A patent/YU275882A/en unknown
- 1982-12-14 YU YU02759/82A patent/YU275982A/en unknown
- 1982-12-15 SU SU823523098A patent/SU1170968A3/en active
- 1982-12-16 NO NO824232A patent/NO824232L/en unknown
- 1982-12-16 CA CA000417934A patent/CA1198125A/en not_active Expired
- 1982-12-16 HU HU824069A patent/HU186649B/en not_active IP Right Cessation
- 1982-12-16 SE SE8207199A patent/SE452612B/en not_active IP Right Cessation
- 1982-12-16 JP JP57221058A patent/JPS58159449A/en active Pending
- 1982-12-16 JP JP57221057A patent/JPS58159446A/en active Pending
- 1982-12-16 SE SE8207198A patent/SE8207198L/en not_active Application Discontinuation
- 1982-12-16 NO NO824233A patent/NO155619C/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DK156567C (en) | 1990-03-05 |
| JPS58159446A (en) | 1983-09-21 |
| KR840002768A (en) | 1984-07-16 |
| YU275882A (en) | 1985-03-20 |
| SE8207199D0 (en) | 1982-12-16 |
| SE8207198L (en) | 1983-06-18 |
| CA1198125A (en) | 1985-12-17 |
| NO824233L (en) | 1983-06-20 |
| NO155619C (en) | 1987-04-29 |
| YU275982A (en) | 1985-03-20 |
| NO824232L (en) | 1983-06-20 |
| DK156567B (en) | 1989-09-11 |
| JPS58159449A (en) | 1983-09-21 |
| SE8207198D0 (en) | 1982-12-16 |
| NO155619B (en) | 1987-01-19 |
| SE8207199L (en) | 1983-06-18 |
| SE452612B (en) | 1987-12-07 |
| DK541982A (en) | 1983-06-18 |
| SU1170968A3 (en) | 1985-07-30 |
| DK542082A (en) | 1983-06-18 |
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