CS207995B1 - Method of making the n-acylated/-/-morfinans - Google Patents
Method of making the n-acylated/-/-morfinans Download PDFInfo
- Publication number
- CS207995B1 CS207995B1 CS277379A CS277379A CS207995B1 CS 207995 B1 CS207995 B1 CS 207995B1 CS 277379 A CS277379 A CS 277379A CS 277379 A CS277379 A CS 277379A CS 207995 B1 CS207995 B1 CS 207995B1
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- formula
- methoxymorphinan
- hydroxy
- acylated
- inorganic base
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- 239000000460 chlorine Substances 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 6
- 150000007529 inorganic bases Chemical class 0.000 claims description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 5
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 4
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 3
- 150000001266 acyl halides Chemical class 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Chemical group 0.000 claims description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- 125000001931 aliphatic group Chemical group 0.000 claims description 2
- 229910000272 alkali metal oxide Inorganic materials 0.000 claims description 2
- 150000001340 alkali metals Chemical class 0.000 claims description 2
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims 1
- 150000004945 aromatic hydrocarbons Chemical group 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 239000000243 solution Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 7
- ZREGHPIWNOPAHK-IXDOHACOSA-N 14-hydroxy-3-methoxymorphinan Chemical compound C1CCC[C@@]2(O)[C@]3([H])NCC[C@@]21C1=CC(OC)=CC=C1C3 ZREGHPIWNOPAHK-IXDOHACOSA-N 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- -1 (-) - 17-acetyl-14β-hydroxy-3-methoxymorphinan Chemical compound 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 150000007530 organic bases Chemical group 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- RWORXZHVOUPMMM-UHFFFAOYSA-N 2,5-dimethylfuran-3-carbonyl chloride Chemical compound CC1=CC(C(Cl)=O)=C(C)O1 RWORXZHVOUPMMM-UHFFFAOYSA-N 0.000 description 1
- OFTKFKYVSBNYEC-UHFFFAOYSA-N 2-furoyl chloride Chemical compound ClC(=O)C1=CC=CO1 OFTKFKYVSBNYEC-UHFFFAOYSA-N 0.000 description 1
- BDUBTLFQHNYXPC-UHFFFAOYSA-N 3-methylbut-2-enoyl chloride Chemical compound CC(C)=CC(Cl)=O BDUBTLFQHNYXPC-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 235000008733 Citrus aurantifolia Nutrition 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- 235000011941 Tilia x europaea Nutrition 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000012455 biphasic mixture Substances 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008241 heterogeneous mixture Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000004571 lime Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- INAXVFBXDYWQFN-XHSDSOJGSA-N morphinan Chemical class C1C2=CC=CC=C2[C@]23CCCC[C@H]3[C@@H]1NCC2 INAXVFBXDYWQFN-XHSDSOJGSA-N 0.000 description 1
- NNJZYCVSLQIWGJ-BAGYTPMASA-N n-cyclobutylcarbonyl-14-hydroxy-3-methoxymorphinan Chemical compound C([C@@]12C3=CC(OC)=CC=C3C[C@@]3([C@@]1(CCCC2)O)[H])CN3C(=O)C1CCC1 NNJZYCVSLQIWGJ-BAGYTPMASA-N 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
(54) Způsob výroby N-acylovaných /-/-morfinanů(54) A method for producing N-acylated / - / - morphinans
Vynález se týká způsobu výroby N-acylovaných (-)-morfinanů obecného vzorce IThe present invention relates to a process for the preparation of the N-acylated (-) morphinans of formula (I)
(I), ve kterém R značí alkyl s 1 až 4 atomy uhlíku nebo zbytky(I) wherein R is C1-C4 alkyl or radicals
Opticky aktivní sloučeniny obecného vzorce I jsou vesměs nové a představují velmi hodnotné meziprodukty při výrobě účinných analgetik.The optically active compounds of the formula I are all novel and are very valuable intermediates in the production of effective analgesics.
Sloučeniny obecného vzorce I, kde R je skupina vinylová, cyklopropylová nebo cyklobutylová, popřípadě substituovaná methylovými skupinami, avšak v racemické formě, se vyrábějí odlišným způsobem podle USA patentu č. 3 819 635 tak, že se (-)-14-hydroxy-3-methoxymorfinan acyluje v přítomnosti terciárních organických bází v bezvodých rozpouštědlech.Compounds of formula (I) wherein R is vinyl, cyclopropyl or cyclobutyl, optionally substituted with methyl groups, but in racemic form, are prepared by a different method according to U.S. Patent No. 3,819,635 by (-) - 14-hydroxy-3. -methoxymorphinan acylates in the presence of tertiary organic bases in anhydrous solvents.
Nevýhodou uvedeného postupu je nutnost používat bezvodých, tj. upravovaných rozpouštědel a nepříjemně páchnoucích organických bází.The disadvantage of this process is the need to use anhydrous, i.e. treated solvents and unpleasant odorous organic bases.
Zmíněné nevýhody odstraňuje způsob podle vynálezu, vycházející ze známého (-)-143-hydroxy-3-methoxymorfinanu (čs. autorské osvědčení č. 191 696) vzorce II σι):The above-mentioned disadvantages are overcome by the process according to the invention, starting from the known (-) - 143-hydroxy-3-methoxymorphinan (cf. No. 191 696) of the formula II σι:
kde R1 je atom vodíku nebo methylskupina nebo jejich kombinace.wherein R 1 is a hydrogen atom or a methyl group, or a combination thereof.
který se podrobí reakci s jedním ekvivalentem acylhalogenidu obecného vzorce IIIwhich is reacted with one equivalent of an acyl halide of formula III
R—CO—X (III), ve kterém R má výše uvedený význam a X značí atom chloru nebo bromu, ve dvoufázové heterogenní soustavě organického rozpouštědla a vodného roztoku anorganické baze, v rozmezí teplot od -5 do +30 °C.R = CO-X (III), wherein R is as defined above and X is chlorine or bromine, in a two-phase heterogeneous system of organic solvent and aqueous inorganic base solution, in the temperature range of -5 to +30 ° C.
Vhodnými organickými rozpouštědly pro provedení reakce jsou například benzen a toluen, chlorované uhlovodíky alifatické řady s 1 až 2 atomy uhlíku, například methylenchlorid, chloroform, chlorid uhličitý nebo dichlorethan, popřípadě aromatické řady, například chlorbenzen.Suitable organic solvents for carrying out the reaction are, for example, benzene and toluene, chlorinated hydrocarbons of the aliphatic series having 1 to 2 carbon atoms, for example methylene chloride, chloroform, carbon tetrachloride or dichloroethane, or aromatic series, for example chlorobenzene.
Jako anorganické baze jsou použitelné hydroxidy, hydrogenuhličitany nebo uhličitany alkalických kovů či kovů alkalických zemin, například uhličitan či hydroxid draselný nebo vápenatý nebo hydrogenuhličitan sodný.Suitable inorganic bases are alkali metal or alkaline earth metal hydroxides, bicarbonates or carbonates, for example potassium or calcium carbonate or hydroxide or sodium bicarbonate.
Podle jedné z možností realizace způsobu podle vynálezu lze například postupovat tak, že se k roztoku nebo suspenzi (-)-14p-hydroxy-3-methoxymorfinanu vzorce II ve směsi zvoleného organického rozpouštědla s vodným roztokem anorganické baze přikapává ekvivalentní množství acylhalogenidu obecného vzorce III. Podle jiné modifikace se reakce provádí tak, že se k roztoku či suspenzi směsi ekvivalentního množství látek vzorce II a obecného vzorce III přidává za teplot —5 až +30 °C vodný roztok anorganické baze.For example, one possibility of carrying out the process of the invention is to add dropwise an equivalent amount of the acyl halide of formula III to a solution or suspension of (-) - 14β-hydroxy-3-methoxymorphinan of formula II in a mixture of a selected organic solvent with an aqueous solution of an inorganic base. In another modification, the reaction is carried out by adding an aqueous solution of an inorganic base to a solution or suspension of a mixture of an equivalent amount of compounds of formula II and formula III at temperatures of -5 ° C to + 30 ° C.
Podle zvláště výhodné formy provedení způsobu podle vynálezu sé reakce provádí v dichlormethanu nebo chloroformu v přítomnosti roztoku uhličitanu sodného nebo draselného za teplot 5 až 20 °C.According to a particularly preferred embodiment of the process according to the invention, the reaction is carried out in dichloromethane or chloroform in the presence of a solution of sodium or potassium carbonate at a temperature of 5 to 20 ° C.
Dále uvedené příklady provedení ilustrují, ale nijak neomezují jak rozsah tak i obecnost způsobu podle vynálezu.The following examples illustrate but do not limit the scope and generality of the process of the invention.
Příklad 1Example 1
K dvoufázové směsi 109,4 g (0,4 mol) (-)-14β-hydroxy-3-methoxymorfinanu vzorce II, 165,8 g (1,2 mol) uhličitanu draselného, 1500 ml chloroformu a 1500 ml vody se po ochlazení na 10 °C přikape za míchání během 1 h 66,8 g (0,41 mol) cyklobutankarbonylbromidu (sloučenina obecného vzorce III, kde R je -CH-CH2-CH2-CH2 a X je atom bromu). Reakční směs se nechá ohřát na teplotu místnosti, organická fáze se oddělí a po promytí 500 ml 3% kyseliny chlorovodíkové, 500 ml vody a vysušení bezvodým síranem sodným se odpaří ve vakuu vodní vývěvy. K odparku se přidá malé množství etheru (nejvýše 50 ml) a vyloučený krystalický (-)-17-cyklobutankarbonyl- 14P-hydroxy-3-methoxymorfinan (sloučenina obecného vzorce I, kde R je -CHCH2CH2CH2) se odsaje. Získá se 138,72 g (97,5 % teorie) látky, která taje v rozmezí 104 až 106 °C.To a biphasic mixture of 109.4 g (0.4 mol) of (-) - 14β-hydroxy-3-methoxymorphinan of formula II, 165.8 g (1.2 mol) of potassium carbonate, 1500 ml of chloroform and 1500 ml of water are cooled at 10 ° C was added dropwise under stirring within 1 h 66.8 g (0.41 mol) cyklobutankarbonylbromidu (compound of formula III wherein R is -CH-CH 2 -CH 2 -CH 2 and X is bromine). The reaction mixture was allowed to warm to room temperature, the organic phase was separated and after washing with 500 ml of 3% hydrochloric acid, 500 ml of water and drying over anhydrous sodium sulfate, it was evaporated in a water pump vacuum. A small amount of ether (no more than 50 mL) was added to the residue and the precipitated crystalline (-) - 17-cyclobutanecarbonyl-14β-hydroxy-3-methoxymorphinan (compound of formula I wherein R is -CHCH 2 CH 2 CH 2 ) was filtered off with suction. 138.72 g (97.5% of theory) of a melting point of 104 DEG-106 DEG C. are obtained.
Příklad 2Example 2
K roztoku 20 g (73,4 mmol) (-)-14P-hydroxy-3-methoxymorfinanu vzorce II ve 200 ml dichlor-, methanu se přidá 250 ml 5% vápenného mléka a po ochlazení na 15 °C se přikape za třepání 3,45 g (44 mmol) acetylchloridu (sloučenina obecného vzorce III, kde R je methyl a X je atom chloru) během 15 minut. Reakční směs se dále třepe 15 minut a oddělí se vrstvy. Organická fáze se promyje 100 ml 6% kyseliny chlorovodíkové, 2 X po 75 ml vody a vysuší se. Odpařením rozpouštědla na rotační vakuové odparce se získá 13,8 g (99,7 % teorie) (-)-17-acetyl- 14P-hydroxy-3-methoxymorfinanu (sloučenina obecného vzorce I, kde R je methyl) v podobě amorfního skla.To a solution of 20 g (73.4 mmol) of (-) - 14β-hydroxy-3-methoxymorphinan of formula II in 200 ml of dichloromethane is added 250 ml of 5% lime milk and after cooling to 15 ° C is added dropwise with shaking. 45 g (44 mmol) of acetyl chloride (compound of formula III, wherein R is methyl and X is chlorine) over 15 minutes. The reaction mixture was shaken for 15 minutes and the layers were separated. The organic phase is washed with 100 ml of 6% hydrochloric acid, 2 x 75 ml of water and dried. Evaporation of the solvent on a rotary evaporator gave 13.8 g (99.7% of theory) of (-) - 17-acetyl-14β-hydroxy-3-methoxymorphinan (compound of formula I wherein R is methyl) as an amorphous glass.
Příklad 3Example 3
K roztoku 20 g (73,4 mmol) (-)-14p-hýdroxy-3-methoxymorfinanu vzorce II ve 350 ml diéhlorethanu se přilije 180 ml 4% roztoku hydroxidu draselného. Reakční směs se ochladí a za míchání se přikape 9,6 g (73,5 mmol) chloridu kyseliny furan-2-karboxyové (sloučenina obecného vzorce III, kde R je -C=CH-CH=CH-O, X je atom chloru) během 15 minut. Organická fáze se oddělí a promyje 50 ml 5% roztoku kyseliny chlorovodíkové a 3 x po 50 ml vody. Po vysušení a odpaření rozpouštědla se získá 24,84 g (92,1 % teorie) amorfního (-)-17-(furan-2-karbonyl)-14p-hydroxy-3-methoxymorfinanu (sloučenina obecného vzorce I, kde R je -C=CH-CH=CH—O.To a solution of 20 g (73.4 mmol) of (-) - 14β-hydroxy-3-methoxymorphinan of formula II in 350 ml of dichloroethane is added 180 ml of a 4% potassium hydroxide solution. The reaction mixture is cooled and 9.6 g (73.5 mmol) of furan-2-carboxylic acid chloride (compound of formula III wherein R is -C -CCH-CH = CH-O, X is chlorine) is added dropwise with stirring. ) within 15 minutes. The organic phase is separated and washed with 50 ml of 5% hydrochloric acid solution and 3 x 50 ml of water. After drying and evaporation of the solvent, 24.84 g (92.1% of theory) of amorphous (-) - 17- (furan-2-carbonyl) -14 [beta] -hydroxy-3-methoxymorphinan (compound of formula I wherein R is - C = CH-CH = CH-O.
Příklad 4Example 4
K roztoku 10,0 g (0,036 mol) (-)-14P-hydroxy-3-methoxymorfinanu vzorce II ve 240 ml chlorbenzenu se přidá 18,0 g (0,21 mol) hydrogenuhličitanu sodného. Směs se ochladí na 5 °C a za míchání se přikape během 15 minut 5,53 g (0,038 lmol)To a solution of 10.0 g (0.036 mol) of (-) - 14β-hydroxy-3-methoxymorphinan of formula II in 240 ml of chlorobenzene is added 18.0 g (0.21 mol) of sodium bicarbonate. The mixture was cooled to 5 ° C and 5.53 g (0.038 lmol) was added dropwise over 15 minutes with stirring.
2,5-dimethyl-3-furoylchloridu (sloučenina obecného vzorce III, kde R je H3C—C=C—CH=C(CH3)—O a X je atom chloru). Směs se míchá ještě 45 minut a organická fáze se oddělí a promyje 30 ml 5% kyseliny chlorovodíkové a 3 X po 40 ml vodý. Odpařením rozpouštědla ve vakuu vodní vývěvy se získá 13,5 g (93,4 % teorie) olejovitého (-)-17-(2,5-dimethylfuran-3karbonyl)-14P-hydroxy-3-methoxymorfinanu (sloučenina obecného vzorce I, kde R je H3C— C=C-CH=C(CH3)-O).2,5-dimethyl-3-furoyl chloride (a compound of formula III wherein R is H 3 C-C = C-CH = C (CH 3 ) -O and X is chlorine). The mixture is stirred for 45 minutes and the organic phase is separated and washed with 30 ml of 5% hydrochloric acid and 3 x 40 ml of aqueous. Evaporation of the solvent in a water pump vacuum gave 13.5 g (93.4% of theory) of oily (-) - 17- (2,5-dimethylfuran-3-carbonyl) -14P-hydroxy-3-methoxymorphinan (a compound of formula I wherein R is H 3 C-C = C-CH = C (CH 3 ) -O).
Příklad 5Example 5
K heterogenní směsi 1,30 g (0,0048 mol) (-)-143-hydroxy-3-methoxymorfinanu vzorce II v 50 ml benzenu nebo toluenu a 1,99 g (0,0144 mol) uhličitanu draselného v 30 ml vody se přidá pri teplotě 5 °C pomalu 1,1 g (0,0093 mol)To a heterogeneous mixture of 1.30 g (0.0048 mol) of (-) - 143-hydroxy-3-methoxymorphinan of formula II in 50 ml of benzene or toluene and 1.99 g (0.0144 mol) of potassium carbonate in 30 ml of water are added. 1.1 g (0.0093 mol) are added slowly at 5 ° C
3,3-dimethylakryloylchloridu (sloučenina obecného vzorce III, kdé R je (CH3)2C=CH— aX je atom 'chloru. Reakční směs se třepe 1,5 h, organická fáze se oddělí, promyje 25 ml 3% kyseliny chlorovodíkové a 2 x po 15 ml vody. Po vysušení síranem sodným se roztok odpaří dokonale ve vakuu vodní vývěvy. Získá se 1,70 g (99,8 % teorie) téměř bezbarvéhoolejovitého(-)-17-(3,3-dimethylakryloyl)-14p-hydroxy-3-methoxymorfinanu (sloučenina obecného vzorce I, kde R je (CH3)2C=CH—).3,3-dimethylacryloyl chloride (formula III, wherein R is (CH 3) 2 C = CH- and X represents a 'chlorine. The reaction mixture was shaken for 1.5 h, the organic phase is separated, washed with 25 ml of 3% hydrochloric acid and twice with 15 ml of water each time, after drying over sodium sulphate, the solution is evaporated off completely in a water-jet vacuum to give 1.70 g (99.8% of theory) of almost colorless (-) - 17- (3,3-dimethylacryloyl) - 14β-hydroxy-3-methoxymorphinan (a compound of formula I wherein R is (CH 3 ) 2 C = CH-).
Claims (3)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS277379A CS207995B1 (en) | 1979-04-21 | 1979-04-21 | Method of making the n-acylated/-/-morfinans |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS277379A CS207995B1 (en) | 1979-04-21 | 1979-04-21 | Method of making the n-acylated/-/-morfinans |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS207995B1 true CS207995B1 (en) | 1981-08-31 |
Family
ID=5365771
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS277379A CS207995B1 (en) | 1979-04-21 | 1979-04-21 | Method of making the n-acylated/-/-morfinans |
Country Status (1)
| Country | Link |
|---|---|
| CS (1) | CS207995B1 (en) |
-
1979
- 1979-04-21 CS CS277379A patent/CS207995B1/en unknown
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR102384529B1 (en) | Process for the preparation of 4-alkoxy-3-(acyl or alkyl)oxypicolinamide | |
| SU1436882A3 (en) | Method of producing diphenylmethyl ether of 7-benzylidene-amino-3-(3-chloro-1-propen-1-yl) - cephem-4-carboxylic acid | |
| JPH0217170A (en) | Production of acid | |
| SU1149873A3 (en) | Method of obtaining threo-2-oxy-(4-methoxyphenyl)-3-(2-nitrophenylthio) propione ester and its version | |
| JPS61215399A (en) | Phosphonate group-containing herbicide and manufacture of intermediate from benzoxazine | |
| US4937367A (en) | Process for the preparation of intermediates for the synthesis of fosfomycin | |
| CS207995B1 (en) | Method of making the n-acylated/-/-morfinans | |
| CS228920B2 (en) | Method of preparing chloromethylester of penicillanic acid derivative | |
| KR100330609B1 (en) | Process for producing 3-isoxazolecarboxylic acid | |
| HU213315B (en) | Process for producing arylacetic acids and their alkali metal salts | |
| RU2095339C1 (en) | Hydroquinone derivatives as free or salt, methods of their synthesis, piperidine derivatives and methods of their synthesis | |
| EP0217376B1 (en) | Process for preparing optically active alpha-haloalkyl-arylketones | |
| KR910000239B1 (en) | Method for preparing methyl 2-tetradecyl glycidate | |
| WO1992015562A2 (en) | Preparation of omega-substituted alkanamide | |
| US4144261A (en) | Process for preparing organothio-aldoxime compounds | |
| SU1201279A1 (en) | Method of producing adamantane 2-derivatives | |
| JP2001502298A (en) | Methods and new intermediates | |
| US5239121A (en) | Process for the preparation of 2-aryl-1,3-propanediols | |
| KR970005309B1 (en) | Process for the preparation of furobenzoisoxazole derivatives | |
| JPS642588B2 (en) | ||
| JPH0657698B2 (en) | Pyrazol oxime derivative and method for producing the same | |
| CA3030555C (en) | Intermediates in processes for the preparation of 4-alkoxy-3-(acyl or alkyl)oxypicolinamides | |
| GB2039474A (en) | Process for preparing organothio-aldoximes | |
| JP3669726B2 (en) | Process for producing optically active 3- (p-alkoxyphenyl) glycidic acid ester derivative | |
| WO2025248390A1 (en) | Process for the preparation of thiophene compounds |