CH295993A - Process for the preparation of 3a, 21-diacetoxy-11,20-diketo-12a, 15, 21-tribromo-16-pregnene. - Google Patents
Process for the preparation of 3a, 21-diacetoxy-11,20-diketo-12a, 15, 21-tribromo-16-pregnene.Info
- Publication number
- CH295993A CH295993A CH295993DA CH295993A CH 295993 A CH295993 A CH 295993A CH 295993D A CH295993D A CH 295993DA CH 295993 A CH295993 A CH 295993A
- Authority
- CH
- Switzerland
- Prior art keywords
- diacetoxy
- diketo
- pregnene
- tribromo
- preparation
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 6
- 238000002360 preparation method Methods 0.000 title description 3
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-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
- 239000002253 acid Substances 0.000 claims description 3
- 238000002844 melting Methods 0.000 claims description 2
- 230000008018 melting Effects 0.000 claims description 2
- 239000002798 polar solvent Substances 0.000 claims description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 2
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 2
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 2
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 229960004544 cortisone Drugs 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- MIPHNLAZISJZFO-LASXQCECSA-N C(C)(=O)O[C@H]1CC2CC[C@H]3[C@@H]4CC[C@H](C(COC(C)=O)=O)[C@]4([C@H](C([C@@H]3[C@]2(CC1)C)=O)Br)C Chemical compound C(C)(=O)O[C@H]1CC2CC[C@H]3[C@@H]4CC[C@H](C(COC(C)=O)=O)[C@]4([C@H](C([C@@H]3[C@]2(CC1)C)=O)Br)C MIPHNLAZISJZFO-LASXQCECSA-N 0.000 description 1
- 239000004593 Epoxy Substances 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Procédé de préparation du 3a, 21-diacétoxy-11,20-dicéto-12a, 15, 21-tribromo-416-prégnène. La prëscnte invention se rapporte à un procédé de préparation du 3a,21-diacétoxy- 11,20 - dicéto -12a,1.5, 21- tribromo - d i6 - pré- gnène (II), avec de bons rendements, à par tir du 3a,21.
- diacétoxy -1.1,20 - dicéto -12a- brorno-prégnane (I). Ce procédé est caracté- risé en ce qu'on traite du 3a,21-diacétoxy- 11, 20 - dicéto -12a - bromo - prégnane (I) au moyen de brome au sein d'un solvant polaire, dans des conditions pratiquement anhydres et en présence d'acide bromhydrique.
1.;1 réaction est illii>;trée par les formules
EMI0001.0028
Comme solv.Lnt polaire, on peut employer un acide aliphatique inférieur, de préférence de l'aeide acétique ou du dioxane.
Le composé obtenu est nouveau; il peut être utilisé pour préparer la cortisone, ainsi que l'illustre ce qui suit: Les atomes de brome des positions <B>15</B> et 21 du composé II peuvent. être facilement enlevés, par exemple par traitement au moyen d'acide iodhydri- que, avec formation de 3a,21-dia.cétoxy-11,20- dicéto-12a-broriro-4l6-prégnène, qui peut.
être transformé en cortisone par diverses voies, comportant l'époxylation de la double liai son en position 16-17, la transformation du composé 16,17-époxy en composé 16-bromo- 17-hydroxy, , le bromage en position 4, suivi du déshydrobromage pour introduire une double liaison en position 4-5 et l'élimina tion des atomes de brome des positions 12 et 16. Ces opérations peuvent être effectuées dans tout ordre approprié et de diverses ma nières.
<I>Exemple:</I> 1200 cm-' d'acide acétique, on ajoute 20 cm- de bromure d\aeétyle et on élimine sois pression réduite la majeure partie de l'acide bromhydrique. Cette élimination n'est toutefois pas totale, du fait de la réaction qui se poursuit lentement entre les deux réactifs, de sorte que le mélange réactionnel contient, après avoir été traité sous pression réduite, une quantité faible, mais suffisante,
d'acide bromliydrique pour catalyser le bro- ma.ge. On constate toutefois que la réaction a lieu plus facilement lorsque la plus grande partie de l'acide bromhi drique a été éliminée. On ajoute ensuite 102 g de 3a,21-diacétoxi- 11, 20 - dicéto -12a - bronro - prégnane (I) et 1.0,2 cm- de brome.
Quand tout le brome a été utilisé, on en rajoute 10,2 cuis, et après <U>eue</U> cette nouvelle quantité a été utilisée, on en rajoute encore 10,2 cm-' et on abandonne au repos pendant 7 jours. On sépare par fil tration les cristaux de composé II, on les lave au moven d'acide acétique et d'éther sec. On concentre la liqueur mère à un faible volume, on ajoute du benzène et on l'élimine sous pression réduite.
L'addition d'éther donne une nouvelle quantité du composé (II), le 3a,21 - diacétoxy -11, 20 - dicéto -.12a,15, 21- tri- bromo-.Jl6-prégnène, qui présente les carac téristiques suivantes: point de fusion 231 à :.'32 C,; aD - --62 (CHC''ls) ; e 235 nia = 8700 (éther). Rendement. global.: 7501o.
1,a nouvelle substance obtenue par le pro cédé selon l'invention se décompose graduelle- rr;ent, même en absence d'air. La nature des produits de décomposition n'est pas connue.
A process for the preparation of 3a, 21-diacetoxy-11,20-diketo-12a, 15, 21-tribromo-416-pregnene. The present invention relates to a process for the preparation of 3a, 21-diacetoxy- 11,20 - diketo -12a, 1.5, 21- tribromo - d i6 - pregnene (II), with good yields, from 3a, 21.
- diacetoxy -1.1,20 - diketo -12a-brorno-pregnan (I). This process is characterized in that 3a, 21-diacetoxy-11, 20-diketo -12a-bromo-pregnan (I) is treated with bromine in a polar solvent under substantially anhydrous conditions. and in the presence of hydrobromic acid.
1.; 1 reaction is illustrated by the formulas
EMI0001.0028
As the polar Lnt solvent, a lower aliphatic acid, preferably acetic acid or dioxane, can be employed.
The compound obtained is new; it can be used to prepare cortisone, as shown in the following: Bromine atoms at positions <B> 15 </B> and 21 of compound II can. be easily removed, for example by treatment with hydriodic acid, with the formation of 3a, 21-dia.cetoxy-11,20-diketo-12a-broriro-4l6-pregnene, which can.
be converted to cortisone by various routes including epoxylation of the double bond at position 16-17, conversion of 16,17-epoxy to 16-bromo-17-hydroxy compound, bromination at position 4, followed dehydrobromage to introduce a double bond at the 4-5 position and the removal of the bromine atoms from the 12 and 16 positions. These operations can be carried out in any suitable order and in various ways.
<I> Example: </I> 1200 cm 3 of acetic acid, 20 cm 3 of ethyl bromide are added and most of the hydrobromic acid is removed under reduced pressure. This elimination is not complete, however, due to the reaction which continues slowly between the two reagents, so that the reaction mixture contains, after having been treated under reduced pressure, a small but sufficient quantity,
hydrobromic acid to catalyze bromace. It is found, however, that the reaction proceeds more easily when most of the bromhideic acid has been removed. Then 102 g of 3a, 21-diacetoxi- 11, 20 - diketo -12a - bronro-pregnan (I) and 1.0.2 cm - of bromine are added.
When all the bromine has been used, we add 10.2 bc, and after <U> had </U> this new quantity has been used, we add another 10.2 cm- 'and we leave to stand for 7 days. The crystals of compound II are separated by filtration, washed with acetic acid and dry ether. The mother liquor is concentrated to a small volume, benzene is added and removed under reduced pressure.
The addition of ether gives a new amount of compound (II), 3a, 21 - diacetoxy -11, 20 - diketo -.12a, 15, 21-tri-bromo-.Jl6-pregnene, which exhibits the characteristics following: melting point 231 to: 32 C; aD - --62 (CHC''ls); e 235 nia = 8700 (ether). Yield. global .: 7501o.
1, a new substance obtained by the process according to the invention gradually decomposes, even in the absence of air. The nature of the decomposition products is not known.
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US295993XA | 1950-05-09 | 1950-05-09 | |
| US250151XA | 1951-01-25 | 1951-01-25 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH295993A true CH295993A (en) | 1954-01-31 |
Family
ID=26699168
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH295993D CH295993A (en) | 1950-05-09 | 1951-04-02 | Process for the preparation of 3a, 21-diacetoxy-11,20-diketo-12a, 15, 21-tribromo-16-pregnene. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH295993A (en) |
-
1951
- 1951-04-02 CH CH295993D patent/CH295993A/en unknown
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