Chemistry of carbon compounds – Miscellaneous organic carbon compounds – C-metal
Patent
1982-03-11
1984-09-18
Roberts, Elbert L.
Chemistry of carbon compounds
Miscellaneous organic carbon compounds
C-metal
2603974, 2603975, 26023955C, 260397, C07J 2100
Patent
active
044723105
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
The invention relates to the subject matter of the claims.
It is known that 3.beta.-acetoxy-5-hydroxy-5.beta.,17.alpha.-pregn-6-ene-21,17-carbolactone can be prepared from 3.beta.-acetoxy-5,6.beta.-epoxy-5.beta.-pregnane-21,17-carbolactone via the intermediate stage of 3.beta.-acetoxy-5-hydroxy-6.alpha.-phenylseleno-5.beta.-pregnane-17,21-car bolactone [Helv. Chim. Acta 62: 2276(1976)].
This process has the disadvantage, however, that highly toxic organoselenium compounds, such as, for example, diphenyldiselenide, are required for the synthesis, the handling of these compounds presenting difficulties on an industrial scale; disposal of the wastes of these compounds can only be made in special dumps, and furthermore these compounds are not likely to be available as a raw material in abundant amounts.
SUMMARY OF THE INVENTION
It is, therefore, an object of the present invention to provide a way for producing 5.beta.-hydroxy-.DELTA..sup.6 -steriods without the use of selenium.
This object has been attained by the process as characterized in the claims.
DETAILED DISCUSSION
Acyl is understood to mean acid residues of up to 12 carbon atoms and derived from acids customarily used in steroid chemistry for esterifications. Preferred acids are carboxylic acids of 1-8 carbon atoms. The carboxylic acids can also be branched, polybasic, or substituted in the usual way, for example by a hydroxy or amino group. Also suitable are cycloaliphatic, aromatic, mixed aromatic-aliphatic, or heterocyclic acids. Preferred acids for the formation of the acylresidue are, for example, acetic acid, propionic acid, caproic acide, trimethylacetic acid, cyclopentylpropionic acid, cyclohexylacetic acid, phenylpropionic acid, phenylacetic acid, dialkylaminoacetic acid, piperidinoacetic acid, succinic acid, and benzoic acid.
Alkyl is understood to mean residues derived from aliphatic hydrocarbons and exhibiting 1-6 carbon atoms, such as, for example, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, and tert.-butyl.
The compounds producible according to the invention are intermediates for the preparation of 3-keto-.DELTA..sup.4 -6.beta.,7.beta.-methylene steroids representing pharmacologically valuable compounds.
The process of this invention is conducted by dissolving the 7.alpha.-chloro-5.beta.,6.beta.-epoxy steroid in an inert protonic solvent and stirring the solution with metallic zinc, for example in pulverized or granular form or in the form of filings, in the presence of an aliphatic carboxylic acid or a dilute mineral acid at between room temperature and about 100.degree. C.
Suitable inert protonic solvents are all those which do not react with the reactants. Examples are aliphatic alcohols, such as methanol, ethanol, n-propanol, and isopropyl alcohol; aliphatic and cycloaliphatic ethers, such as diisopropyl ether, tetrahydrofuran, and dioxane, as well as water.
Besides acetic acid, which is preferably employed, formic acid and propionic acid are likewise suitable as aliphatic carboxylic acids for conducting the reaction of the invention. However, the use of a dilute mineral acid is also possible, such as hydrochloric acid or sulfuric acid.
The acid utilized is employed in excess. The excess amount is 30-100 times the quantity (mol equivalents). The acid is suitably used in a concentration of 0.2-1.0 mole/liter.
The reaction mixture is heated, a temperature range of 40.degree.-70.degree. C. being preferred.
The duration of the reaction is about 0.5-7 hours, this time being dependent on the starting material employed and especially on the temperature.
The course of the reaction according to the invention was surprising since, under the reaction conditions applied (acidic, temperature above room temperature), it would have to be expected that the thus-formed 5.beta.-hydroxy-.DELTA..sup.6 - steroids would be converted by allyl rearrangement into corresponding secondary products. For it is known from the work performed by Morand [P. Morand and A. van Tongerloo, Steroids 21: 47-61 (1973)] that 5-hyd
REFERENCES:
patent: 3798213 (1974-03-01), Arth
patent: 3883512 (1975-05-01), Stache et al.
patent: 3890304 (1975-06-01), Weier
patent: 3966714 (1976-06-01), Philippson
patent: 4119627 (1978-10-01), Wieland
Helv. Chim. Acta., vol. 62, (1979), No. 7, p. 2277 relied on, Article by Wieland.
Steroids 21:47-61, (1973).
Bittler Dieter
Laurent Henry
Nickisch Klaus
Nickolson Robert
Wiechert Rudolf
Roberts Elbert L.
Schering Aktiengesellschaft
LandOfFree
5.beta.-Hydroxy-.DELTA..sup.6 -steroids and process for the prep does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with 5.beta.-Hydroxy-.DELTA..sup.6 -steroids and process for the prep, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and 5.beta.-Hydroxy-.DELTA..sup.6 -steroids and process for the prep will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-793088