DE1214222B - Process for the production of 3, 5-cyclo-6-oxo-steroids of the Pregnan, Pregnen, Androstan- and Androstan series - Google Patents

Description

FEDERAL REPUBLIC OF GERMANY

GERMAN

PATENT OFFICE

EDITORIAL

Int. Cl .:

Number:
File number:
Registration date:
Display day:

C 07 c

German class: 12 ο -25/02

1 214 222
F40303IVb / 12 ο
July 23, 1963
April 14, 1966

From German patent specification 1092 013 and U.S. Patent 3,002,969 is known. 3,5-cyclo-6-hydroxysteroids by treating with Chromic acid in glacial acetic acid or with chromic acid in pyridine to give the corresponding 3,5-cyclo-6-oxosteroids to oxidize.

There has now been a process for the preparation of 3,5-cyclo-6-oxo-steroids of the Pregnan-, Pregnen-, Androstane and androstene series found, which is characterized in that a 3,5-cyclo-6 / i-hydroxy-pregnan-, -pregnen, -androstane or -androsten, which has no further primary or secondary hydroxyl groups, with lead tetraacetate oxidized in dimethyl sulfoxide.

The reaction sequence of this process is shown, for example, in the following scheme:

Process for the production of 3,5-CyCIo-O-OXO-steroids of the Pregnan-, Pregnen-, Androstan-
and androsten series

Applicant:

Farbwerke Hoechst Aktiengesellschaft

formerly Master Lucius & Brüning, Frankfurt / M.

Named as inventor:
Dr. Werner Fritsch, Neuenhain (Taunus);
Dr. Werner Haede, Hofheim (Taunus);
Dr. Ulrich Stächen, Frankfurt / M.-Höchst

Pb (OAc) ₄

Dimethyl sulfoxide

To carry out the process, an SS-cyclo-o / i-hydroxy-steroid of the pregnane, pregnen, androstane or androstane series is dissolved or suspended in dimethyl sulfoxide, preferably in eight to twelve times the amount by weight of this solvent. Solid lead tetraacetate is then added, preferably in excess and expediently with stirring. The reaction is carried out at temperatures between 10 and 8O ⁰ C, preferably between 20 and 40 ° C, and advantageously in a nitrogen atmosphere. Under these conditions, the reaction is generally complete after 60 to 90 minutes. To remove the excess lead tetraacetate, a hydroxyl-containing compound, advantageously a glycol, such as ethylene glycol, is added. The oxidized steroid is then precipitated by adding water. The salts of the divalent lead remain in solution. For cleaning, washing with water is generally sufficient, since the process products are obtained in very good yield and high purity. if

desired, z. B. recrystallized from petroleum ether will.

As starting materials for the process come z. B. the following 3,5-cyclo-6 /) '- hydroxy steroids into consideration:

3,5-CycIo-6 /) '- hydroxypregnan-20-one,
3,5-Cyclo-6 /: MiydiOxy- I ¹⁶ -pregnen-20-one,
3,5-Cyclo-6p'-hydiOxy-andiOstan-17-one,

androstane

as well as other pregnan, pregnen, androstan and androstenedivatives, none except in the 6 / j position have primary or secondary hydroxyl groups.

The advantages of the present method over the known ones consist in one essential shorter reaction time, in a more convenient work-up, in a lower solvent consumption and in significantly better, partly quantitative yields.

609 558/418

The products of the process are for the most part valuable as intermediate products for manufacture known from physiologically highly effective 6-methyl steroids. On the other hand, new connections are also as indicated in Example 3, prepared by this process.

example 1

15.9 g of lead tetraacetate are added to a solution of 8.34 g of 3,5-cyclo-6 / miydroxypregnan-20-one in 66 ecm of dimethyl sulfoxide with exclusion of moisture, stirring and in a nitrogen atmosphere. The temperature is kept at 30 to 35 ° C. by cooling. After the heat of reaction has subsided, the mixture is cooled to room temperature. After a total of 90 minutes, 6 ecm of ethylene glycol and 15Qccm of water are stirred in one after the other with moderate cooling. Here crystallized 3,5-cyclo-6-oxo-pregnan-20-one of which is filtered, washed with water and dried in vacuo at 50 ⁰ C. 8.2 g (98.8% of theory) with a melting point of 164 ° C. (Kofjer melt bank) are obtained.

B is ρ ie 1 2
3,5-CyCIo-O-OXO-. 1 ¹⁶ -pregnen-20-on

2.84g of 3,5-cyclo-6fj-hydroxy-. I ¹⁶ -pregnen-20-one are, as described in Example 1, reacted in 22 ecm of dimethyl sulfoxide with 5.4 g of lead tetraacetate. After 75 minutes, 2 ecm of ethylene glycol and 50 ecm of water are stirred in and the steroid is isolated as described. 2.73 g (96.5% of theory) of 3,5-cyclo-6-oxo- ^1G- pregnen-20-one with a melting point of 182 to 184 ° C. (Kofler melt bench) are obtained.

B ei s ρ i e1 3
3,5-Cycio-6-oxo-17-ethylene-dioxo-androstane

8.1 g of 3,5-cyclo- 6ß- hydroxy-17-ethylene-dioxyandrostane, manufactured according to Bull. Soc. Chim., 1960, p. 298, are, as described in Example 1, reacted in 70 ecm of dimethyl sulfoxide with 17 g of lead tetraacetate. After 90 minutes, 7 ecm of ethylene glycol and 150 ecm of water are stirred in. After the usual workup, the reaction product is recrystallized from a little petroleum ether of boiling point 60 to 95 ⁰ C. This gives 6.29 g (78% of theory) of 3,5 - cyclo - 6 - oxo -17 - ethylene - dioxy group androstan of melting point 118-120 ⁰ C.

Claims (2)

Patent claims: 1. Process for the preparation of 3,5-cyclo-6-oxo-steroids the Pregnan, Pregnen, Androstan and Androstan series, characterized in that that one has a 3,5-cyclo-6 / i-hydroxy-pregnane, -pregnen, -androstan or -androsten, which no further primary or secondary hydroxyl groups, oxidized with lead tetraacetate in dimethyl sulfoxide. 2. The method according to claim 1, characterized in that temperatures between 20 and 40 ⁰ C are used.