DE1211193B - Process for the production of delta 17 (20) -Pregnenes - Google Patents

Description

FEDERAL REPUBLIC OF GERMANY

GERMAN

PATENT OFFICE

EDITORIAL

Int. σ .:

C 07 c

German class: 12 ο -25/05

Number: 1211193

File number: Sch 32383 IV b / 12 ο

Filing date: November 24, 1962

Opening day: February 24, 1966

Applicant:

Schering Aktiengesellschaft,

Berlin 65, Mullerstr. 170/172

Process for the production of

The work of Barton in Journ. Chem. Soc, London, 1962, p. 470 ff., Which describes a new reaction of aldehyde and ketone hydrazones with iodine in a basic reaction medium, it can be seen that the elimination of hydrogen iodide from 3-hydroxy-20,20-diiodine-z ) ⁵ -pregnen leads to 3-hydroxy-20-iodine ~ zl ³ · ²⁰ -pregnadiene.

It has now been found that in 20-mono-halogen steroids, contrary to the Barton method, the 20-halogen atom is surprisingly split off as hydrogen halide ^{with the formation of a hemicyclic zl 17} ( ^{20 'double bond.}

The invention thus relates to a process for the preparation of / I ¹⁷ < ² °) -Pregnenes of the general formula

St = CH • CH ₃ ²

where St is any cyclopentano-perhydro- where with a mixture of petroleum ether-benzene phenanthren-17-yl radical, which is characterized by initially a small amount zi ^{4 '20} ( ²¹ > -pregnadien-3-one that a corresponding steroid ao and then 820 mg (79% of theory) zl ⁴ · ¹⁷ -of the general formula Pregnadien-3-one are eluted.

Named as inventor:

Dr. Bernhard Krieger, Senne II (district of Bielefeld);

Dr. Egbert Blanke,

Dr. Emanuel Kaspar, Kamen

St-CH • X • CH ₃

where St has the meaning given above and X is a halogen atom, preferably bromine or iodine, dar- as represents, in an organic solvent with a base, preferably with alcoholic alkali or Alkaline earth solution, treated and, after the hydrogen halide has been split off, the reaction mixture for the purpose of isolation and purification of the resulting ^ i7 (20) _steroid worked up in the usual way.

The steroids of the formula St = CH · CH ₃ prepared according to the invention are valuable intermediate products for the preparation of medicaments. The corresponding, highly effective steroid hormones, such as, for example, the corresponding zl ⁴ -androstendiones, 17 "-hydroxyprogesterones, testosterones, ethynyltestosterones and the corticoid hormones, can easily be produced from them by appropriate combination of known synthesis steps.

example 1

1.5 g of 20-iodo / l * -pregnen-3-one are dissolved in 100 ml of ethanol with 120 ml of a lO ° / o solution of potassium hydroxide in ethanol and heated I ³ Ai hours under reflux. The cooled reaction solution is then poured into ice water, extracted with methylene chloride, the organic phase washed neutral, dried over sodium sulfate and, after filtration, evaporated to dryness in vacuo. The residue is chromatographed over an acid of neutral aluminum oxide,

Example 2

250 mg of 20-chloro-zl ⁴ -pregnen-3-one (prepared from the corresponding 20-carboxylic acid with carbon tetrachloride in the presence of lead tetraacetate, mp 186 to 187 ° C) are dissolved in 10 ecm of ethanol, with 5 ecm of a 5% > igen solution of potassium hydroxide in ethanol and heated under reflux for 19 hours. The cooled reaction solution is then poured into ice water with hydrochloric acid and worked up analogously to Example 1. The crude product is chromatographed over neutral silica gel (10% water). ^{I 4} · ¹⁷ -pregnadien-3-one, which corresponds to the substance obtained from Example 1 in terms of melting point and mixed melting point, is eluted with a mixture of petroleum ether-benzene. After recrystallization from isopropanol, the melting point rises to 136 to 137 ° C.

Example 3

100 mg of 20-bromo-zd ⁴ -pregnen-3-one are reacted and worked up analogously to Example 2 to give zi ^{4 '17} -pregnadien-3-one. The isolated crude product is chromatographed on neutral silica gel. With a mixture of petroleum ether-benzene Λ ⁴ · ¹⁷ < ²⁰ > pregnadien-3-one is eluted, which melts at 134 to 136 ° C after recrystallization from isopropanol. The mixed melting point with the product obtained in Example 1 shows no depression.

609 509/416

Claims (2)

Example 4 2.1 g of 20-iodine-zl ^4- pregnen-3-one, 2.2 g of sodium methylate and 50 ml of propanol are heated to 100 ° C. for 5 hours with stirring and worked up as in Example 1. The yield of zi ^{4 '17} -pregnadien-3-one is 80% of theory. Example 5 1.5 g of 20-iodine-5 /? - pregnan-3-one are dissolved in 120 ml of ethanol, with 120 ml. to a 10% solution of potassium hydroxide in ethanol. The reaction mixture is refluxed for 2 hours and then worked up as in Example 1. The isolated crude product is recrystallized from acetone, giving 875 mg of ¹⁷ -5 / 3-pregnen-3-one with a melting point of 130 to 131 ° C, Example 6 ' 1 g of 20-iodine / i ⁴ ' ⁶ -pregnadien-3-one are dissolved in 75 ml of ao ethanol, treated with 100 ml of a 10% solution of potassium hydroxide in ethanol and; Heated under reflux for 2 hours and then worked up as in Example 1. After the isolated crude product has been filtered through silica gel and recrystallized from isopropyl ether, 415 mg of zl * ' ⁶ ' ¹⁷ -pregnatrien-3-one are obtained. ybmv melting point 103 to 104 ° C; UV max. = 284ίημν; ε = 24,000. Paterite claims: . 1. . Process for the production of AWo) - pregnenes of the general formula St = CH-CH ₃ ' where St "is a cyclopentano-perhydrophenanthren-17-yl radical means, characterized in that a corresponding steroid of the general formula St-CH • X • CH ₃ where St has the meaning given above and X is a halogen atom, preferably bromine or iodine, treated in an organic solvent with a base, preferably with an alcoholic alkali or alkaline earth solution and, after the hydrogen halide has been split off, the reaction mixture for the purpose of isolating and purifying the obtained / d ⁱ⁷ ' ^ao ' steroids worked up in the usual way. 2. The method according to claim 1, characterized in that 20-iodine ^ ⁴ -pregnen-3-one is used as the starting product. 609 509/416 2.66 © Bundesdruckerei Berlin