DE1195306B - Process for the preparation of a 3-methyl-7-keto-8- (3'-ketobutyl) -3, 4- [3'-acyloxy-cyclo-pentano- (2 ', 1')] decahydronaphthalene compound - Google Patents

Description

FEDERAL REPUBLIC OF GERMANY

GERMAN

PATENT OFFICE

EDITORIAL

Int. Cl .:

C07c

German KL: 12 ο -25/04

Number: 1195 306

File number: L 40409IV b / 12 ο

Filing date: November 7, 1961

Opening day: June 24, 1965

The main patent 1 142 603 relates to a process which consists in the fact that a Zl ⁸ -3-methyl-7-keto-8- (3 "-ketobutyl) -3,4, - ß'-acyloxy-cyclopentano- (2nd ', l')] - octahydronaphthalene compound of the general formula I.

OAc

where Ac is the residue of a lower aliphatic or an aromatic carboxylic acid, catalytic hydrogenated, the corresponding 3-methyl-7-keto-8- (3 "-ketobutyl) -3,4- [3'-acyloxy-cyclopentanoso (2 ', r)] - decahydronaphthalene compound of the formula

OAc

receives, which is also called sweet
4,5-seco-androstane can be designated. According to the main patent, the latter compound is then cyclized to 19-nor-testosterone with the aid of dehydrating agents.

According to the process of the cited main patent, the catalytic hydrogenation of the double bond in the 8 (9) position of the compound I is carried out in a conventional manner, that is to say in a neutral medium, a colorless resin being obtained which, as has subsequently been determined, for mostly from a mixture of approximately equal amounts of the two [9a, 10a H] and [9ß, 100 H] isomers of 3,5-dioxo-17/9-acyloxy-19-nor-4,5-seco- androstans, of which only the [9 <x, 10 «H] isomer provides the 19-nor-testosterone of natural configuration by cyclization.

The present invention relates to an improvement in the hydrogenation stage of the process of the main patent which consists in the fact that the catalytic hydrogenation process for the preparation of a 3-methyl-

7-keto-8- (3 "-ketobutyl) -3,4- [3'-acyloxy-cyclo-

pentano (2 ', l')] decahydronaphthalm compound

Addendum to the patent: 1142 603

Applicant:
Roussel-Uclaf, Paris

Representative:

Dr. F. Zumstein,

Dipl.-Chem. Dr. rer. nat. E. Assmann

and Dipl.-Chem. Dr. R. Koenigsberger,

Patent Attorneys, Munich 2, Bräuhausstr. 4th

Named as inventor:

Dr.-Ing. Gerard Nomine, Noisy-le-Sec, Seine;
Dr. Robert Bucourt, Villiers-le-Bel, Seine-et-Oise; Andre Pierdet, Noisy-le-Sec, Seine (France)

Claimed priority:

France of November 16, 1960 (844101)

the double bond in the 8 (9) position of the compound I in a basic medium, in particular in a pH around 11, in the presence of a catalyst based on palladium hydroxide.

According to a particular embodiment of the invention In the process, the basicity of the reaction medium is made by adding triethylamine causes.

As a result of the inventive modification of the process of the main patent, the hydrogenation takes place stereospecific, and the yield of the desired [9a, 10a H] isomer is increased considerably.

The new process results in using the starting compound I in which Ac represents = C ₆ H ₅ CO, a yield of 95 ° / o ^of pure 3,5-dioxo-17 / J-benzoyloxy [9a, 10a H] -19- nor-4,5-seco-androstane, which is easy to crystallize.

509 597/427

The following example serves to explain the process according to the invention in more detail.

example

Production of 3-methyl-7-keto-8- (3 "-ketobutyl) -

3,4- [3'-benzoyloxy-cyclopentano- (2 ', r)] - decahydro-

naphthalene (compound II, Ac = C ₈ H ₅ CO)

550 mg of ^{I 8} -3-methyl-7-keto-8- (3 "-ketobutyl) -3,4- [3'-benzoyloxy-cyclopentano- (2 ', l')] - octahydronaphthalene (compound I, Ac = C ₆ H ₅ CO), mp = 117 ° C, [ «] £ = + 43 ° (c = 1% methanol) which was obtained as described in the main Patent 1,142,603, in 40 cc of 95 ⁰ ZoIg ⁶ D ¹ Ethanol The solution is added to a suspension of 40 mg palladium-carbon, which contains 15% palladium hydroxide, in 5 cm alcohol.Then a 10% alcoholic triethylamine solution is added until the pH value 11 is reached The mixture is then stirred under a hydrogen atmosphere for IVs hours. It is filtered, the filtrate is evaporated to dryness in vacuo and the residue is crystallized from isopropyl ether. Yield: 431 mg (about 78%) of 3-methyl-7-keto-8- (3 " -ketobutyl) -3,4- [3'-benzoyloxy - cyclopentano - (2 ', I ¹ )] - decahydronaphthalene of the current F. = 114 ⁰ C. [«] !? = + 48 ° (c = 1% methanol). 17% of the identical product can still be obtained from the mother liquor. The product results in the form of colorless needles which are soluble in methanol and ethanol and insoluble in water and dilute aqueous acids and alkalis.

Analysis: Cg ₆ H ₈₈ O ₄ = 396.5
Calculated ... C 75.72%, H 8.13%;
found ... C75.7%, H8.2%.

UV spectrum in ethanol:

ληαχ. = 230 πιμ, s == 14 300,
Xg _111x- = 273 ΐημ, β = 940,
haax. = 280 ηαμ, e = 765.

Rotary dispersion:

[Ml ₄₀₀ = +190

[M] ₃₁₇ = - 3480 (minimum)

[M] ₃₀₀ = + 290

[M] ₃₅₀ = - 245

[M] ₃₀₉ = - 2650 (inflexion)

[M] ₂₈₇ = 4880 (peak)

Claims (2)

Patent claims: 1. A process for the preparation of a 3-methyl-7-keto-8- (3 "-ketobutyl) -3,4- [3'-acyloxy-cyclopentano- (2 ', 1')] -decahydronaphthalene compound by catalytic hydrogenation of a corresponding one ii ⁸ -3-Methyl-7-keto-8- (3 "-ketobutyl) -3,4- [3'-acyloxy-cyclopentano- (2 ', l')] - octahydronaphthalene compound according to Patent 1,142603, characterized in that that here the 8 (9) double bond of the zl ⁸ -3-methyl-7-keto-8- (3 "-ketobutyl) - 3,4 - [3'-acyloxy-cyclopentano - (2 ', 1' )] - octahydronaphthalene compound of the general formula OAc wherein Ac is the residue of a lower aliphatic or an aromatic carboxylic acid, in basic medium, in particular at a pH value around 11, in the presence of a catalyst on the Hydrogenated based on palladium hydroxide. 2. The method according to claim 1, characterized in that the basic pH value of the Reaction medium is effected with the help of triethylamine. Considered publications:
Angewandte Chemie, Vol. 72 (1960), p. 728. 509 597/427 6.65 © Bundesdruckerei Berlin