DE1178430B - Process for the preparation of esters of 17ª ‡ -Aethinyloestr-5 (10) -en-3ª ‰, 17ª ‰ -diol - Google Patents

Description

Process for the preparation of esters of 17ot-ethynylestr-5 (10) -en-3p, 17β-diol The invention relates to a process for the preparation of esters of 17α-ethynylestr-5 (10) -en-3β, 17β-diol, which can be represented on the basis of the general structural formula where R and R 'denote alkanoyl radicals whose alkyl part contains fewer than 7 carbon atoms.

The alkanoyl radicals R and R 'can be methyl, ethyl, Contain propyl, butyl, pentyl and hexyl groups and their branched-chain isomers.

The diesters of the general formula (1) can be prepared by adding a compound of the general formula in which one of the symbols R ″ and R ... represents hydrogen and the other represents hydrogen or an alkanoyl radical as defined above, is reacted in a manner known per se with a corresponding acylating agent.

Particularly useful acylating agents are the fatty acid anhydrides, z. B. acetic anhydride, the acylation with a fatty acid anhydride is preferably carried out in the presence of a base, such as an organic base such as pyridine, or even one inorganic base, such as potassium carbonate, which is used in the course of the reaction to neutralize the acid formed. Other suitable acylating agents are the fatty acid halides, z. B. acetyl chloride; the acylation with a fatty acid halide is preferably carried out in the presence of a base.

The diesters of the general formula (1) are preferably prepared using the corresponding 17a-ethynylestr-5 (10) -en-3fl, 17fl-diol, i.e. H. a compound of the general formula (II), where R "and R ... are hydrogen, using at least two equivalents of the acylating agent. In this way, the alkanoyl groups of the diester are the same.

In addition, the diesters of the general formula (1) can also be prepared from the corresponding 17β-alkanoyloxy-17α-äthinylöstr-5 (10) -en-3β-ol, i.e. H. a compound of the general formula (II), where R " denotes hydrogen and R ... denotes an alkanoyl radical as defined above, or from the corresponding 3ß-alkanoyloxy-17a-ethinylestr-5 (10) -en-17fl-ol, i.e. a compound of the general formula (11), where R "is an alkanoyl radical as defined above and R ... is hydrogen, the acylating agent being used in at least an equivalent amount. Accordingly, the alkanoyl groups of the diester can be the same or different.

The compounds prepared according to the invention show advantageous ones pharmacological properties. For example, they act as estrogenic agents, which do not have the side effect of causing a progestational overgrowth of the Evoke endometrial gland.

The following examples explain the process according to the invention. In these examples, the Temperatures in degrees Celsius and the amounts of substance are given as parts by weight, unless otherwise specified.

Example I A mixture of 17a-IOTeilen Athinylöstr-5 (I0) -ene-3.beta., 1 7.beta.-diol, 54 parts of acetic anhydride and 98 parts of pyridine under nitrogen is refluxed for about 21/2 hours at reflux, then cooled with ice and water diluted and extracted with ethyl acetate. The organic extract is washed with water, dried over anhydrous sodium sulfate and concentrated to dryness in vacuo. The partially crystalline residue is recrystallized from methanol, giving a 17α-Athinylöstr-5 (10) -en-3β, 17β-diol-3,17-diacetate with a melting point of about 127 to 129 ' ; [aj "# +87 ' (chloroform). This compound shows characteristic infrared peaks at approximately 3.03, 5.72 and 8.00 to 8.12 # t.

Is used instead in the process described in the preceding paragraph method in an equivalent amount 17.beta.-acetoxy-1 7a-äthinylöstr-5 (I0) -ene-3.beta.-ol or 3.beta.-acetoxy-17a-äthinylöstr-5 (I0) -en-17.beta. -ol, the same 17α-ethynylestr-5 (10) -en-3fl, 17β-diol-3,17-diacetate is obtained. EXAMPLE 11 A mixture of I part 17α-ethynylestr-5 (10) -en-3β, 17β-diol, 5 parts propionic anhydride and 9.8 parts pyridine is refluxed under nitrogen for about 2112 hours. The reaction mixture is then cooled, diluted with ice and water and extracted with ethyl acetate. The organic extract is washed with water, dried over anhydrous sodium sulfate and concentrated to dryness under reduced pressure to give pure 17α-ethynylestr-5 (10) -en-3fl, 17β-diol-3,17-dipropionate in the form of 01 . It is characterized by maxima in the infrared spectrum at around 3.00, 5.75 and 8.12 to 8.30 # t.

If instead, in the process described in the previous section, an equivalent amount of 17fl-propionoxy-17a-äthinylöstr-5 (I0) -en-3ß-ol or 3ß-propionoxy-17a: -äthinylöstr-5 (I0) -en-17fl- ol is used, the same 17α-ethynylestr-5 (10) -en-3p, 17β-diol-3,17-dipropionate is formed. Example 111 A solution of 2 parts 17a-Athinyl- 1 7fl-propionoxyöstr-5 (I0) -en-3fl-ol in 25Teilen oxygen reiern propionyl chloride and 100 parts of pyridine is allowed to about 18 hours at room temperature under a nitrogen atmosphere and then poured into 2000Teile cold water . The precipitate is collected by filtration and recrystallized from methanol; it arises 17a-Athinylöstr-5 (I0) -ene-3.beta., 1 7fl-diol-3,17-dipropionate.

Claims (1)

Claim: Process for the preparation of esters of 17α-Athinylöstr-5 (I0) -en-3β, 17β-diol of the general formula in which R and R 'denote alkanoyl radicals whose alkyl group contains fewer than 7 carbon atoms, characterized in that a compound of the general formula in which one of the symbols R "and R"' is hydrogen and the other is hydrogen or an alkanoyl radical as defined above represents, is reacted in a manner known per se with a corresponding acylating agent.