NO167294B - PROCEDURE FOR THE PREPARATION OF 16,17-ACETAL SUBSTITUTED STEROIDS. - Google Patents
PROCEDURE FOR THE PREPARATION OF 16,17-ACETAL SUBSTITUTED STEROIDS. Download PDFInfo
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- NO167294B NO167294B NO87873567A NO873567A NO167294B NO 167294 B NO167294 B NO 167294B NO 87873567 A NO87873567 A NO 87873567A NO 873567 A NO873567 A NO 873567A NO 167294 B NO167294 B NO 167294B
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- Prior art keywords
- preparation
- compound
- hydrogen
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- diene
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- 238000000034 method Methods 0.000 title claims description 7
- 238000002360 preparation method Methods 0.000 title claims description 5
- 150000003431 steroids Chemical class 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 13
- 239000000460 chlorine Substances 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 125000002252 acyl group Chemical group 0.000 claims description 3
- 239000003054 catalyst Substances 0.000 claims description 3
- 150000007522 mineralic acids Chemical class 0.000 claims description 3
- 125000002947 alkylene group Chemical group 0.000 claims description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 2
- 229920006395 saturated elastomer Polymers 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 13
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 10
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N Butyraldehyde Chemical compound CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- FJJYHTVHBVXEEQ-UHFFFAOYSA-N 2,2-dimethylpropanal Chemical compound CC(C)(C)C=O FJJYHTVHBVXEEQ-UHFFFAOYSA-N 0.000 description 4
- YGHRJJRRZDOVPD-UHFFFAOYSA-N 3-methylbutanal Chemical compound CC(C)CC=O YGHRJJRRZDOVPD-UHFFFAOYSA-N 0.000 description 4
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- HFJRKMMYBMWEAD-UHFFFAOYSA-N dodecanal Chemical compound CCCCCCCCCCCC=O HFJRKMMYBMWEAD-UHFFFAOYSA-N 0.000 description 4
- FXHGMKSSBGDXIY-UHFFFAOYSA-N heptanal Chemical compound CCCCCCC=O FXHGMKSSBGDXIY-UHFFFAOYSA-N 0.000 description 4
- JARKCYVAAOWBJS-UHFFFAOYSA-N hexanal Chemical compound CCCCCC=O JARKCYVAAOWBJS-UHFFFAOYSA-N 0.000 description 4
- GYHFUZHODSMOHU-UHFFFAOYSA-N nonanal Chemical compound CCCCCCCCC=O GYHFUZHODSMOHU-UHFFFAOYSA-N 0.000 description 4
- NUJGJRNETVAIRJ-UHFFFAOYSA-N octanal Chemical compound CCCCCCCC=O NUJGJRNETVAIRJ-UHFFFAOYSA-N 0.000 description 4
- HGBOYTHUEUWSSQ-UHFFFAOYSA-N pentanal Chemical compound CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 4
- -1 steroid compounds Chemical class 0.000 description 4
- QIEPWCSVQYUPIY-LEKSSAKUSA-N Delta(1)-progesterone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 QIEPWCSVQYUPIY-LEKSSAKUSA-N 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- AMIMRNSIRUDHCM-UHFFFAOYSA-N Isopropylaldehyde Chemical compound CC(C)C=O AMIMRNSIRUDHCM-UHFFFAOYSA-N 0.000 description 2
- IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 235000015320 potassium carbonate Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 1
- QWOJMRHUQHTCJG-UHFFFAOYSA-N CC([CH2-])=O Chemical compound CC([CH2-])=O QWOJMRHUQHTCJG-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
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- WBGKWQHBNHJJPZ-LECWWXJVSA-N desonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O WBGKWQHBNHJJPZ-LECWWXJVSA-N 0.000 description 1
- 229960003662 desonide Drugs 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 229940043075 fluocinolone Drugs 0.000 description 1
- FEBLZLNTKCEFIT-VSXGLTOVSA-N fluocinolone acetonide Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O FEBLZLNTKCEFIT-VSXGLTOVSA-N 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000003420 transacetalization reaction Methods 0.000 description 1
- 229960005294 triamcinolone Drugs 0.000 description 1
- GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Landscapes
- Steroid Compounds (AREA)
Description
Foreliggende oppfinnelse vedrører en ny fremgangsmåte for fremstilling av steroid-mellomprodukter, som kan anvendes for oppnåelse av glukokortikosteroider som er i besittelse av høy anti-inflammatorisk virkning på anbringelsesstedet og lav glukokortikoid systemisk virkning. Slike glukokortikosteroider er beskrevet i norsk patentsøknad 861313. The present invention relates to a new method for the production of steroid intermediates, which can be used to obtain glucocorticosteroids that have a high anti-inflammatory effect at the site of application and a low glucocorticoid systemic effect. Such glucocorticosteroids are described in Norwegian patent application 861313.
Ifølge foreliggende forbindelse er det således tilveiebragt en fremgangsmåte for fremstilling av forbindelser med den generelle formel: eller en stereoisomer forbindelse derav, hvor 1,2-stillingen er mettet eller er en dobbeltbinding, er valgt fra hydrogen, fluor, klor og brom, X2 er valgt fra hydrogen, fluor, klor og brom, R2 er valgt fra rette og forgrenede hydrokarbonkjeder med 1-10 karbonatomer, og R7 er hydrogen eller en acylgruppe med 1-10 karbonatomer ordnet i en rett eller forgrenet kjede, og denne fremgangsmåten er kjenne-tegnet ved at man i et oppløsningsmiddel valgt fra halogenerte alkylener omsetter en forbindelse med formelen: According to the present compound, there is thus provided a method for the preparation of compounds of the general formula: or a stereoisomeric compound thereof, where the 1,2-position is saturated or is a double bond, is selected from hydrogen, fluorine, chlorine and bromine, X2 is selected from hydrogen, fluorine, chlorine and bromine, R2 is selected from straight and branched hydrocarbon chains with 1-10 carbon atoms, and R7 is hydrogen or an acyl group with 1-10 carbon atoms arranged in a straight or branched chain, and this method is known drawn by reacting a compound with the formula in a solvent selected from halogenated alkylenes:
med en forbindelse med formelen ItøCHO hvor X^, X2, R2» R7°g ~ =~^ : har de ovenfor angitte betydninger, . i nærvær av en sterk, uorganisk syre som katalysator. with a compound of the formula ItøCHO where X^, X2, R2» R7°g ~ =~^ : have the meanings indicated above, . in the presence of a strong, inorganic acid as a catalyst.
Ved fremstilling steroidforbindelsene som er beskrevet i norsk patentsøknad 861313 blir en> forbindelse med formlene X, XI og XII oksydert til den tilsvarende 17e-karboksylsyren: hvor de sammenhengende og brutte linjer mellom C-l og C-2 representerer en enkelt- eller dobbeltbinding; Xj_, X2, Ri og R£ har de ovenfor angitte betydninger; og R7 er hydrogen eller acyl med 1-10 karbonatomer anordnet i en rett eller forgrenet kjede. When producing the steroid compounds described in Norwegian patent application 861313, a compound with the formulas X, XI and XII is oxidized to the corresponding 17e-carboxylic acid: where the continuous and broken lines between C-1 and C-2 represent a single or double bond; Xj_, X2, Ri and R£ have the meanings indicated above; and R7 is hydrogen or acyl with 1-10 carbon atoms arranged in a straight or branched chain.
Som utgangsmaterialer for forbindelsene beskrevet i norsk patentsøknad 861313 benyttes forbindelser med formlene X, XI og XII. De fremstilles som nevnt ovenfor ved transacetaliser-ing av de tilsvarende 16oc, 17a-acetonidene. hvor de sammenhengende og brutte linjene mellom og C2 representerer en enkelt eller dobbelt binding og X^, X2 og R7 har de ovenfor angitte betydninger, med et aldehyd med formelen: Compounds with the formulas X, XI and XII are used as starting materials for the compounds described in Norwegian patent application 861313. They are prepared as mentioned above by transacetalization of the corresponding 16oc, 17a-acetonides. where the continuous and broken lines between and C2 represent a single or double bond and X^, X2 and R7 have the meanings given above, with an aldehyde of the formula:
hvor R2 har den ovenfor angitte betydning. where R2 has the meaning given above.
Aldehydet er fortrinnsvis acetaldehyd, propanal, butanal, isobutanal, pentanal, 3-metylbutanal, 2,2-dimetylpropanal, heksanal, heptanal, oktanal, nonanal og dodekanal. Reaksjonen utføres ved tilsetning av steroidet til en oppløsning av aldehydet sammen med en sterk uorganisk syre som katalysator, fortrinnsvis perklorsyre eller saltsyre, i et halogenert hydrokarbon, fortrinnsvis metylenklorid eller kloroform. The aldehyde is preferably acetaldehyde, propanal, butanal, isobutanal, pentanal, 3-methylbutanal, 2,2-dimethylpropanal, hexanal, heptanal, octanal, nonanal and dodecanal. The reaction is carried out by adding the steroid to a solution of the aldehyde together with a strong inorganic acid as a catalyst, preferably perchloric acid or hydrochloric acid, in a halogenated hydrocarbon, preferably methylene chloride or chloroform.
Utførelseseksempler Execution examples
Oppfinnelsen skal ytterligere illustreres ved følgende eksempler. I eksemplene anvendes en strømningshastighet på 2,5 ml/cm2 *t—* ved de preparative kromatografiske utfør-^" eisene. Molekylvekter er i alle eksempler bestemt med elektronstøt-massespektrometri og smeltepunktene på et Leitz Wetzlar-varmtrinn-mikroskop. Alle HPLC-analyser (HPLC - High Performance Liquid Ghromatography) ble foretatt på en Waters jjBondapak C^g-kolonne (300 x 3,9 mm indre diameter) med en strømningshastighet på 1,0 ml/min. og med etanol-vann i forhold mellom 50:50 og 60:40 som mobil fase, dersom ikke annet er angitt. The invention shall be further illustrated by the following examples. In the examples, a flow rate of 2.5 ml/cm2 *t—* is used in the preparative chromatographic run-^" ices. Molecular weights are determined in all examples with electron impact mass spectrometry and the melting points on a Leitz Wetzlar hot-stage microscope. All HPLC- analyzes (HPLC - High Performance Liquid Chromatography) were carried out on a Waters jjBondapak C^g column (300 x 3.9 mm inner diameter) with a flow rate of 1.0 ml/min and with ethanol-water ratio of 50 :50 and 60:40 as mobile phase, unless otherwise stated.
Eksempel 1 Example 1
Dette eksempel angir en fremgangsmåte for fremstilling av (22RS)-, (22R)- og (22S)-lle,21-dihydroksypregna-l,4-dien-3,20-dion-16cx, 17a-acetaler. This example sets forth a method for the preparation of (22RS)-, (22R)- and (22S)-II,21-dihydroxypregna-1,4-diene-3,20-dione-16cx,17a-acetals.
Fremstilling av (22RS)-, (22R)- og (22S)-16a,17a-butyliden-dioksy-6a , 9a-dif luor-lle ,21-dihydroksypregna-l ,4-dien-3,20-dion. Preparation of (22RS)-, (22R)- and (22S)-16a,17a-butylidene-dioxy-6a,9a-difluoro-lle,21-dihydroxypregna-l,4-diene-3,20-dione.
A. Til en oppløsning av 1,0 g 6a,9a-difluor-lle,21-dihyd-roksy-16a , 17a- [ (1-me ty le ty I i den )bis( oksy )]pregna-l ,4-dien-3,20-dion i 500 ml metylenklorid ble det tilsatt 0,30 ml nydestillert n-butanal og 2 ml 725É perklorsyre. Reaksjons-blandingen ble hensatt i 24 timer ved 33<*>C under omrøring, ekstrahert med vandig kaliumkarbonat og vann, tørket over natriumsulfat og lnndampet. Resten ble oppløst i metylenklorid og utfelt med petroleumeter, hvilket ga 848 mg (22RS)-16a,17a-butylidendioksy-6a,9a-di fluor-lle,21-dihydroksy-pregna-1,4-dien-3,20-dion. HPLC-analyse viste 93% renhet og forholdet 12/88 mellom 22S- og 22R-epimerene. A. To a solution of 1.0 g of 6a,9a-difluoro-lle,21-dihydroxy-16a ,17a- [ (1-methyl le ty I in the )bis( oxy )]pregna-l,4 -diene-3,20-dione in 500 ml of methylene chloride, 0.30 ml of freshly distilled n-butanal and 2 ml of 725É perchloric acid were added. The reaction mixture was left for 24 hours at 33<*>C with stirring, extracted with aqueous potassium carbonate and water, dried over sodium sulfate and evaporated. The residue was dissolved in methylene chloride and precipitated with petroleum ether, yielding 848 mg of (22RS)-16α,17α-butylidenedioxy-6α,9α-difluoro-lle,21-dihydroxy-pregna-1,4-diene-3,20-dione . HPLC analysis showed 93% purity and a ratio of 12/88 between the 22S and 22R epimers.
B. Likeledes, ved å følge metoden angitt i eksempelet ovenfor, gir erstatning av utgangsmaterialet 6a,9a-difluor-lle ,21-dihydroksy-16a7l7a-[(1-metyletyliden)bis(oksy)]pregna-1,4-dien-3,20-dion i eksempelet ovenfor med llB,21-di-hydroksy-16a,17a-[(1-metyletyliden)bis(oksy)pregna-l,4-dien-3,20-dion, eller med 9a-fluor- eller 6a-fluor-lle,21-di hy dr ok sy-16a , 17a-[ (1-metyl etyl iden )bis(oksy)] pregna-1,4-dien-3,20-dion og omsetning av en slik forbindelse med acetaldehyd, propanal, butanal, isobutanal, pentanal, 3-metylbutanal, 2,2-dimetylpropanal, heksanal, heptanal, oktanal, nonanal og dodecanal, ikke-fluorerte og fluorerte ikke-symmetrlske (22RS)-, (22R)- og (22S )-lle,16a, 17a,21-tetrahydroksypregna-1,4-dien-3,20-dion 16,17a-acetaler. B. Likewise, following the method indicated in the example above, substitution of the starting material 6a,9a-difluoro-lle,21-dihydroxy-16a7l7a-[(1-methylethylidene)bis(oxy)]pregna-1,4-diene- 3,20-dione in the above example with 11B,21-dihydroxy-16a,17a-[(1-methylethylidene)bis(oxy)pregna-1,4-diene-3,20-dione, or with 9a-fluoro - or 6a-fluoro-lle,21-dihydr oksy-16a, 17a-[(1-methyl ethylidene)bis(oxy)] pregna-1,4-diene-3,20-dione and reaction of a such compound with acetaldehyde, propanal, butanal, isobutanal, pentanal, 3-methylbutanal, 2,2-dimethylpropanal, hexanal, heptanal, octanal, nonanal and dodecanal, non-fluorinated and fluorinated unsymmetrical (22RS)-, (22R)- and (22 S )-lle,16a,17a,21-tetrahydroxypregna-1,4-diene-3,20-dione 16,17a-acetals.
Eksempel 2 Example 2
A. Prednacinolon (250 mg; 0,6 mmol) ble oppløst i 75 ml CH2CI2. n-butanal (130 mg; 1,8 mmol) og 7056 perklorsyre (0,025 ml) ble tilsatt. Oppløsningen ble omrørt ved 33°C i 15 timer. Den gule oppløsningen ble vasket med 2 x 10 ml 10* K2CO3 og 4 x 10 ml H2O, tørket og inndampet. Dette ga (22RS)-16a,17a-butylidendioksy-lle,21-dihydroksypregna-l,4-dien-3,20-dIon. A. Prednacinolone (250 mg; 0.6 mmol) was dissolved in 75 mL CH 2 Cl 2 . n-Butanal (130 mg; 1.8 mmol) and 7056 perchloric acid (0.025 mL) were added. The solution was stirred at 33°C for 15 hours. The yellow solution was washed with 2 x 10 ml 10* K2CO3 and 4 x 10 ml H2O, dried and evaporated. This gave (22RS)-16α,17α-butylidenedioxy-lle,21-dihydroxypregna-1,4-diene-3,20-dIon.
Utbytte: 257 mg (97,7*). HPLC ga 91,1* renhet. Uomsatt acetonid utgjør 7,49b av urenhetene. Epimerforhold 14,6/85,4. Yield: 257 mg (97.7*). HPLC gave 91.1* purity. Unreacted acetonide makes up 7.49b of the impurities. Epimer ratio 14.6/85.4.
B. Triamcinolon (0,5 g; 1,1 mmol) ble oppløst i 150 ml CH2CI2. n-butanal (260 mg; 3,6 mmol) og 70* perklorsyre (0,22 ml) ble tilsatt. Blandingen ble omrørt ved 33'C i 16 timer. CH2Cl2~fasen ble anbrakt i en skylletrakt og reaksjonskolben vasket flere ganger med 10 ml K2CO3 og CH2CI2, respektivt. Oppløsningen ble deretter vasket med 2 x 10 ml 10* K2CO3 og 4 x 10 ml H2O, tørket og inndampet. Dette ga (22RS)-16a,17a-butyl idendioksy-9a- f luor-lle , 21-dihydroksypregna-l ,4-dien-3,20-dion. B. Triamcinolone (0.5 g; 1.1 mmol) was dissolved in 150 mL CH 2 Cl 2 . n-Butanal (260 mg; 3.6 mmol) and 70% perchloric acid (0.22 mL) were added. The mixture was stirred at 33°C for 16 hours. The CH2Cl2 phase was placed in a rinsing funnel and the reaction flask was washed several times with 10 ml of K2CO3 and CH2CI2, respectively. The solution was then washed with 2 x 10 ml 10* K 2 CO 3 and 4 x 10 ml H 2 O, dried and evaporated. This gave (22RS)-16α,17α-butyl idenedioxy-9α-fluoro-lle, 21-dihydroxypregna-1,4-diene-3,20-dione.
Utbytte: 438 mg (84,9*). HPLC ga 80,2* renhet. Epimerforhold 19/81. C. Fluocinolon (0,5 g; 1,1 mmol) ble oppløst i 150 ml CH2C12-n-butanal (260 mg; 3,6 mmol) og 70* perklorsyre (0,22 ml) ble tilsatt. Blandingen ble omrørt ved 33'C i 24 timer. CH2CI2-fasen ble anbrakt i skilletrakt. Reaksjonskolben ble vasket flere ganger med 15 ml 10* K2CO3 og CB^C^f respektivt. Oppløsningen ble vasket med 2 x 15 ml 10* K2CO3 og 4 x 15 ml H2O, tørket og inndampet. Dette ga (22RS)-16a,17a-butyliden-dioksy-6a , 9a-di f luor-lle , 21-dihydroksypregna-1,4-dien-3,20-dion. Yield: 438 mg (84.9*). HPLC gave 80.2* purity. Epimer ratio 19/81. C. Fluocinolone (0.5 g; 1.1 mmol) was dissolved in 150 mL of CH 2 Cl 2 -n-butanal (260 mg; 3.6 mmol) and 70% perchloric acid (0.22 mL) was added. The mixture was stirred at 33°C for 24 hours. The CH2Cl2 phase was placed in a separatory funnel. The reaction flask was washed several times with 15 ml of 10* K 2 CO 3 and CB^C^f respectively. The solution was washed with 2 x 15 ml 10* K 2 CO 3 and 4 x 15 ml H 2 O, dried and evaporated. This gave (22RS)-16α,17α-butylidene-dioxy-6α,9α-difluorine,21-dihydroxypregna-1,4-diene-3,20-dione.
Utbytte: 513 mg (100*). HPLC ga 97,4* renhet. Epimerforhold 8,6/91,4. Yield: 513 mg (100*). HPLC gave 97.4* purity. Epimer ratio 8.6/91.4.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NO873567A NO167294C (en) | 1985-04-04 | 1987-08-24 | PROCEDURE FOR THE PREPARATION OF 16,17-ACETAL SUBSTITUTED STEROIDS. |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE8501693A SE8501693D0 (en) | 1985-04-04 | 1985-04-04 | NOVEL 16,17-ACETALSUBSTITUTED ANDROSTANE-17BETA-CARBOXYLIC ACID ESTERS |
| NO864917A NO165680C (en) | 1985-04-04 | 1986-12-08 | ANDROSTAN-17 BETA CARBOXYLIC ACID COMPOUNDS. |
| NO873567A NO167294C (en) | 1985-04-04 | 1987-08-24 | PROCEDURE FOR THE PREPARATION OF 16,17-ACETAL SUBSTITUTED STEROIDS. |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| NO873567L NO873567L (en) | 1986-10-06 |
| NO873567D0 NO873567D0 (en) | 1987-08-24 |
| NO167294B true NO167294B (en) | 1991-07-15 |
| NO167294C NO167294C (en) | 1991-10-23 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO873567A NO167294C (en) | 1985-04-04 | 1987-08-24 | PROCEDURE FOR THE PREPARATION OF 16,17-ACETAL SUBSTITUTED STEROIDS. |
Country Status (1)
| Country | Link |
|---|---|
| NO (1) | NO167294C (en) |
-
1987
- 1987-08-24 NO NO873567A patent/NO167294C/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NO873567D0 (en) | 1987-08-24 |
| NO167294C (en) | 1991-10-23 |
| NO873567L (en) | 1986-10-06 |
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