DE1568767C3 - 3-ethylidene-3 alpha, beta-methyl-perhydrobenz square bracket on square bracket to indene and a process for the production of 3-ethylidene-3 alpha, beta-methyl perhydrobenz square bracket on square bracket to indene and 3 beta- ( 1 -hydroxyethyl) - 3 alpha beta methylbenzene square bracket to square bracket to indene - Google Patents

Description

CH-CH,

20th

25th

in which, on an asymmetric carbon atom, a solid line indicates β-stereo configuration, a dotted line indicates α-stereo configuration and a wavy line indicates α or / J stereo configuration, R _{1 is} hydrogen or lower-alkyl and Z is one of the groups

OR ₂

3a / f-methyl-benz [e] indene is obtained by adding the Α ring of the tetracyclic steroid structure. 3a / f-methyl-benz [e] indenes with a hydroxyl or oxo group in the 3-position can therefore be converted into steroids of the androstane series. 3a / i-methyl-benz [e] -indenes with an acetyl or 1-hydroxyethyl group in the 3-position can be converted into steroids of the pregnane series. Steroids of the 17- / i-pregnancy series are particularly valuable compounds and can be prepared from 3a / i-methylbenz [e] -indenes with a 3 / i-acetyl or 3ß- (l'-hydroxyethyl) side chain. The problem with this access route was that 3ß-methylbenz [e] indenes with a 3 / i-acetyl or 3 /? - (l'-hydroxyethyl) side chain were much less readily available than 3a / f-methylbenz [e] indene with a 3-hydroxy or 3-oxo group. The present invention now aims to provide a process for the synthesis of 3ß-acetyl- or 3/3 - (V - hydroxyethyl) - 3a / i - methyl - benz [e] indenes from 3-oxo-3a ^ -methyl-benz [ e] indenen to deliver. 3-Oxo-3a / i-methyl-benz [e] indenes can be obtained from 3-hydroxy -3ass-methyl-benz [e] indenes by oxidation with conventional oxidizing agents, for example chromium trioxide in pyridine or dimethylformamide.

The expression "3a / S-methyl-benz [e] indene" used here and in the following refers, if not otherwise stated, on compounds of the following formula structure:

(IV)

35

O-

O'

or

in which R _{2 is} hydrogen, lower alkyl or tetrahydropyranyl and R _{3 is} lower alkylidene.

The present invention relates to a process for the preparation of 3 (l'-hydroxyethyl) -3a / i-methylbenz [e] indenes. The process according to the invention is characterized in that (a) a 3-oxo-3ä _j Ö-methyl-benz [e] indene in which oxo groups other than those in the 3-position are present in protected form is reacted with ethylidene triphenylphosphorane, if desired present Splitting off oxo protective groups, reducing oxo groups to hydroxyl groups and converting the latter into lower alkoxy or tetrahydropyranyloxy groups and (b) treating a 3-ethylidene-3a / i-methyl-benz [e] indene with a hydrogen boride and then with hydroperoxide.

Recently, steroid syntheses have become known, in which the tetracyclic steroid molecule from a The expression "3a / 3-methyl-benz [e] indene" relates to compounds with the above structure regardless the degree of saturation, if not different (e.g. with a prefix like Perhydro, which means full saturation indicated).

The method according to the invention comprises 2 stages. In the first stage, a 3-oxo-3a / 3-methylbenz [e] indene is treated with ethylidene triphenylphosphorane. A 3-ethylidene-3a / I-methylbenz [e] indene is obtained. 3-ethylidene-3a /? - methyl-benz [e] indene are new compounds. In the second stage of the process according to the invention, the 3-ethylidene-3ass-methyl-benz [e] indene is subjected to treatment with a hydrogen boride and then with hydroperoxide, the desired 3ß- (l'-hydroxyethyl) -3ass-methyl-benz [e] indene is obtained. The 3β - (V - hydroxyethyl) - 3a / f - methyl - benz [e] indene can then be oxidized with a common oxidizing agent, e.g. B. Chromium trioxide in pyridine or dimethylformamide can be converted into a 3ß - acetyl - 3 & ß - methylbenz [e] indene.

The term hydrogen boride as used here refers to a radical formed from a trivalent Boron and one hydrogen atom. As a result, this remainder has two free valences and can can be represented as follows:

Β —Η

The boron hydrogen can e.g. B. applied as borane

be, with the expression borane BH ₃ in all of its formulas, z. B. is meant as borane per se or diborane or as a complex, or a lower alkyl borane or lower dialkyl borane.

In the 3-oxo-3a / i-methylben / [e] indene used as the starting material, all oxo groups other than those in the 3-position should be protected protected form during the entire process and regenerates the oxo group, if desired, only after the 30th (1'-Ilydroxyäthyl) -3a // - methyl-benz [e] indene has been obtained. On the other hand, the protective group can also be split off after treatment with the alkylidene-triphenylphosphorane, which gives the 3-ethylidene-3a /? - methyl-benz [e] indene. The protective group can be inserted and split off in a manner known per se. Oxo groups other than the 3-position can be protected, for example, by ketalization, ie by reaction with a lower alkanediol in the form of a lower alkylenedioxy substitute and then, if desired, regenerated in a manner known per se, /. B- <J ^{by mild} acid hydrolysis.

Furthermore, oxo groups other than those in the 3-position can be selectively converted into hydroxyl groups will. The oxo groups can then, if desired, by common oxidizing agents, for. B. by oxidation with chromium trioxide in acidic solution (e.g. acetic acid). If desired, this can be done with the oxidation of the hydroxy group of the hydroxyethyl side chain, which is im Course of the method according to the invention is introduced in the 3-position, are connected.

The presence of double bonds in the starting material 3a /? - methyl-benz [e] indene z. B. between the carbon atoms 1 and 2, the 'carbon atoms 8 and 9 or the carbon atoms 5 and 5 a leads to the attack on these double bonds by the hydrogen boric acid hydroperoxide treatment, without affecting the introduction of the hydroxyethyl side group in the 30-position will. However, since the products obtained here contain a hydroxy substituent on the ring, this represents a special case of the invention, and preferably one uses / ends as a starting material Perhydro-3a /> methyl-benz [e] indene.

Since substituents such as those with a carbonyl radical (carboxyl groups, esters, amides, alkanoyl groups) and nitriles would be attacked by the hydrogen boride treatment in the process according to the invention, rruin preferably uses a 3-oxo-3a / i-methyl-benz [e] indene as the starting product does not contain any such substituents. In the presence of other substituents, such as lower-alkyl, halo, hydroxy, ether groups such as lower-alkoxy, lower-alkyleniioxy and tetrahydropyranyloxy, which are not attacked by the process measures, the process according to the invention can of course be used. The 3-oxo-3a / i-methylenzene [e] indene used as the starting material can thus contain a number of substituents in the molecule without affecting the process according to the invention. For example, s lower-alkyl groups, hydroxyl groups, lower-alkoxy, lower-alkylenedioxy, tetrahydropyranylxy groups and halogen in the positions 1, 2, 4, 5, α *. 6, 7, 8.9. 9 a. Ί Ό and also in the 3a / i-methyl group.
A particularly important aspect of the process according to the invention is that it contains 3ß - (1 '- hydroxyethyl) - 3a /? - methyl - benz [e] indene, ie compounds in which the substituents in the 3 and 3 positions are 0, ie in the cis position to one another, provides. It has surprisingly been found that the stereochemical relationship obtained in the process according to the invention is independent of the stereochemistry of the rest of the benz [e] in the molecule. The method according to the invention is thus applicable to cis-anti-trans (5a / ?, 9a / 3: 3a / S, 9ba) and transanti-trans (5aa, 9a0: 3a / S, 9ba) Benz [e] indene, and this represents a preferred embodiment of the present invention. The method according to the invention can also be applied to other possible stereo configurations such as cis-syn-trans (5aa, 9aa: 3a /?, 9ba). The stereoconfiguration of substituents present in the 6- and / or 7-position also does not affect the stereospecificity of the introduction of the hydroxyethyl side chain into the 3-position. The inventive method thus provides 3 / S- (I'-Hydroxy äthy I) -3a / S-methyl-benz [e] indene and is based on Benz [e] indene with z. B. a 60-methyl or 6a-methyl group and / or a 7a-hydroxy or 70-hydroxy group can be used.

The first stage of the process according to the invention consists in the implementation of a 3-oxo-3a /? - methylbenz [e] indene, in which all other than the 3-position oxo groups are protected, with ethylidene triphenylphosphorane, the corresponding 3-ethylidene-3a / S-methyl-benz [e] indene is obtained. The reaction is expediently carried out in a neutral, non-ketonic organic solvent accomplished. Organic solvents that can be used are, for example, ethers, z. B. lower alkyl ethers such as diethyl ether, dioxane, tetrahydrofuran; aromatic hydrocarbons such as Benzene, xylene, cumene; lower dialkyl alkanoyl amides such as dimethylformamide or dimethylacetamide; or Dimethyl sulfoxide. The reaction with ethylidene triphenylphosphorane is preferably carried out in the same way Solvent from in which the Äthylidenetriphenylphosphoran was formed. Since the latter usually is made in dimethyl sulfoxide, this compound is also a preferred solvent for the implementation of 3-oxo-3a / i-methyl-benz [e] -indene with ethylidene triphenylphosphorane.

The reaction desÄthylidentriphenylphosphorans with the 3-oxo-3a0-methyl-benz [e] indene is conveniently carried out at temperatures between room temperature and about 120 ⁰ C or the boiling point of the reaction mixture, this lower wofern is performed. It has been found that the preferred temperature range for conducting the reaction is between about 40 and about 8O ⁰ C. Particularly good results are obtained when the reaction is carried out between about 40 and about 60.degree. The amounts of reagents employed are not critical, and an excess of each can be used. However, it has proven advantageous to use a molar excess of ethylidene triphenylphosphorane. It is particularly advantageous to use about 4 moles of ethylidenetriphenylphosphorane per mole of 3-oxo-3ass-methyl-benz [e] indene.

The reaction described above gives 3-ethylidene-3ass-methyl-benz [e] indene, preferably in the perhydroform, or else with double bonds in the ring as indicated above. Particularly preferred

are 3-ethylidene - 3ass-methyl - perhydro - benz [e] indenes the formula

CH

in which on an asymmetric carbon atom a solid line / i-stereoconfiguration, a dotted line a-stereoconfiguration and a wavy line α- or / ϊ-stereoconfiguration indicates, R _{1 is} hydrogen or lower-alkyl (especially methyl), Z is one of the groups

OR ₂

C = O

in which R _{2 is} hydrogen, lower alkyl or tetrahydropyranyl and R _{3 is} lower alkylidene.

The 3-ethylidene-3a / i-methyl-benz [e] indene of the formula I may also contain substituents other than those specifically indicated, those indicated directly however, represent the preferred.

In the second stage of the process according to the invention, a 3-ethylidene-3a /? -Methyl-benz [e] indene is treated with a boron hydrogen and then with hydroperoxide. This stage gives the desired 3ß- ( 1'-hydroxyethyl) -3ajS-methyl-benz [e] indene with a cis configuration between the substituents in 3 and 3a. The hydrogen boride used for the treatment of 3-ethylidene-3ass-methylbenz [e] indene can be obtained, for example, from borane, alkylborane or dialkylborane. The term alkylborane embraces compounds of the formula

RBH ₂ (II)

in which R is a saturated, straight-chain or branched hydrocarbon radical such as lower-alkyl, for example t-hexyl (where the compound of Formula II is 2,3-dimethyl-2-butylborane).

The term dialkylborane embraces compounds of the formula

R ₉ bra

(III)

in which R can in each case be identical or different and is a saturated, straight-chain or branched one Hydrogen radical such as lower alkyl, for example isoamyl (if both radicals R are isoamyl, the compound of the formula III is bis- (3-methyl-l-butyl) borane), represents.

The treatment with the boron hydrogen is preferably carried out in an organic solvent, for example in an ether such as a lower alkyl ether, e.g. B. diethyl ether or in dioxane or tetrahydrofuran. If borane is used, this can either be added to the reaction mixture or generated in situ. The reaction with the borane is usually around -20

carried out to about 40 ⁰ C, preferably between 0 ⁰ C and room temperature. Room temperature is preferred for simplicity.

The borane is expediently in the form of a borane complex, e.g. B. (with an ether. A borane: tetrahydrofuran combination has proven to be particularly useful, it can be added dissolved in tetrahydrofuran. On the other hand, the borane can also be generated in situ from a hydride and an acid, of which one partner or both For example, an alkali metal borohydride (such as sodium borohydride, potassium borohydride or lithium borohydride) and a Lewis acid (such as boron trifluoride or sulfuric acid) can be added to the reaction mixture to generate the borane in situ. On the other hand, a non-boron hydride and a boron acid can be added to the reaction mixture Examples of non-boron-containing hydrides are alkali metal hydrides, such as sodium hydride and alkali metal aluminum hydrides, such as lithium aluminum hydride. Examples of boron-containing Lewis acids are boron trihalides, for example boron trifluoride or boron trichloride fe the process according to the invention was used, at least 1 mole of hydrogen boride (calculated as BH) should be used for every mole of 3-ethylidene-3a / 3-methyl-benz [e] indene. If the 3-oxo-3ass-methyl-benz [e] indene used as the starting material contains one or more double bonds, a proportionally larger amount of hydrogen boride should be used to allow the hydroboration of these double bonds to proceed. In the case of non-olefinic 3-oxo-3a / S-methyl-benz [e] indene starting materials, it is expedient to use between 1 and about 2 moles of hydrogen boride for every mole of 3-ethylidene-3ass-methylbenz [e] indene. Has it turned out to be special? Proven to be advantageous, for example, between 1 and I ¹ Z ₂ moles of borane to use for every mole of 3-ethylidene-3a / i-methylbenz [e] indene.

Following the hydrogen boride treatment, the reaction mixture was brought to a pH greater than 7 d. H. made alkaline, this can usually be done through Addition of an alkali hydroxide such as caustic soda; or by adding a salt of a strong base with a weak acid or by adding a suitable buffer solution or any other conventional solution Means happen. Hydroperoxide is then added to the reaction mixture. The hydroperoxide should be indene in at least an equimolar amount, based on a non-olefinic 3-oxo-3a ^ -methylbenz [e] as starting material; where the 3-oxo-3a / 9-methyl-benz [e] indene has one or more double bonds, more should be used (see above Explanations about the amount of the boron hydrogen to be used), but it can also be desired if used in excess. The Hydroper oxide is usually in the form of an aqueous Solution added. ' The reaction can be carried out at room temperature, more expedient it becomes wise at lower temperatures, ζ. Β carried out at around 0 ° C.

As stated above, the process according to the invention provides 3 // - (l'-hydroxyethyl) -3a / i-methyl-benz [e]

indene. The desired 3 / i configuration is independent of the configurations, e.g. B. in position 5, 5 a, 6, 7, 8, 9, 9 a and 9 b. For example, using the process according to the invention, 3a / ?, 6 / f-dimethyl-3,7-dioxo-5ass, 9ba-perhydro-benz [e] indene with suitable protection of the 7-oxo group in 3ß- (l'- Hydroxyethyl) - 3a / ?, 6 / i - dimethyl - 7 - oxo - 5a / f, 9ass, 9ba - perhydro - benz [e] indene and 3aß, 6a - dimethyl-3,7 - dioxo - 5aa, 9a.ß , 9ba - perhydro - benz [e] indene can be converted into 3aß, 6a - dimethyl - 3 β - (Γ - hydroxyethyl) - 7 - oxo- ίο 5aa, 9aß, 9ba - perhydro - benz [e] indene. In the course of these conversions, new 3-ethylidene compounds, which are outlined by formula I, are obtained as intermediates. For example, after protecting the 7-oxo group by ketalization with formation of a 7,7-ethylenedioxy group, the new intermediates 3a / y, 6 / i-dimethyl-7,7-ethylenedioxy-3-ethylidene-5a / ?, 9ass, 9ba are obtained - perhydro - benz [e] indene and 3ass, 6a - dimethyl - 7,7 - ethylenedioxy - 3 - ethylidene - 5aa, 9a / J, 9ba-perhydro-benz [e] indene.

As stated above, the 3 / j- (r-hydroxyethyl) -3ass-methyl-benz [e] -indenes obtainable according to the invention and the 3/3-acetyl derivatives obtainable therefrom are of value as intermediates for the production of the tetracyclic steroid structure. If the benz [e] indene obtained by the process according to the invention contains a group which can be converted into an oxo group in the 7-position, it can be converted from this by methods known per se. Condensation of the 7 - oxo - benz [e] indene with methyl vinyl ketone forms the Α ring of the steroid structure. 3β - (V - hydroxyethyl) - 3a /? - 6ß - dimethyl - 7 - oxo-5a /? - 9a / i-9ba-perhydro-benz [e] indene produces 20-hydroxy-3-oxo- Δ ⁴ -9ß, 10a-pregnane and 3 / on condensation with methyl vinyl ketone 3-Acetyl-3a / 3,6a-dimethyl-7 - 0x0 - 5aa - 9ass - 9ba - perhydro - benz [ejinden supplies progesterone in a similar manner by condensation with methyl vinyl ketone.

In the following examples the temperatures are given in degrees Celsius.

example 1

3 g of a 53.4% sodium hydride dispersion in mineral oil (67 mmol sodium hydride) was mixed 3 times with Washed hexane and blown dry under nitrogen. After adding 75 ml of dimethyl sulfoxide the mixture was heated to 70 to 75 ° under nitrogen and with stirring until the evolution of hydrogen ceased warmed up. After about 30 minutes a light green solution resulted which cooled to room temperature would. The cooled solution was then rapidly mixed with a solution of 27.9 g (67 mmol) of ethyl triphenylphosphonium iodide added in 100 ml of dimethyl sulfoxide, with a deep red solution of Äthylidentriphenylphosphoran which was used in the reactions described below.

A solution of 3 g'7,7 - ethylenedioxy - 3 - oxo-

y // pylXl
in 100 ml of dimethyl sulfoxide, a solution of • 59 mmol of ethylidene triphenylphosphorane in 150 ml of dimethyl sulfoxide was added rapidly with stirring and nitrogen. After 15 minutes of stirring at room temperature the reaction mixture 3 _^3/4 hour at 55 was heated to 60 °. Thin-layer chromatography then shows only traces of the starting material present. The reaction mixture was then cooled, poured into ice water and extracted 3 times with petroleum ether. The organic extracts
the washed 3 times with water, dried over sodium sulfate, concentrated and applied to a short column of aluminum oxide (activity level I). Elution with petroleum ether gave 7,7-ethylenedioxy-3-ethylidene - 3a / ?, 6/3 - dimethyl - 5a & 9a / ?, 9ba - perhydrobenz [e] indene, which slowly crystallized. Melting point 60 to 71 °.

Gas chromatography showed this material to be a mixture of 92% cis and 8% trans isomers depicted. The melting point of one from ether — methanol recrystallized sample was 73 to 75 °.

2.467 g of 7-ethylenedioxy-3-ethylidene- 3ass, 6ß- dimethyl-5ass, 9a / S, 9ba-perhydro-benz [e] indene (the crude product obtained above) was dissolved in 100 ml of dry tetrahydrofuran and treated with 12 ml of a 1 molar BH ₃ solution in tetrahydrofuran treated under nitrogen and stirring. After I ¹ I ₂ hours aqueous sodium hydroxide solution was added with 30 ml of 10%, the mixture cooled to 0 ° with 12 ml of 30% hydroperoxide in the course of 10 minutes, was added. After stirring at 0 ° for 1 hour, water and ether were added, and the ethereal phase was washed with 10% strength sodium hydrogen sulfite solution and water and dried over sodium sulfate. Evaporation of the solvent gave crude 7,7-ethylenedioxy - 3 β - (IR -1 - hydroxyethyl) - 3a £, 6 / S - dimethyl-5a / 3,9a / S, 9ba-perhydrobenz [e] indene as an oil .

2.486 g of crude 7,7-ethylenedioxy-3 / S- (lR-l-hydroxyethyl) - 3 & ßfiss - dimethyl - 5a / S, 9a / S, 9ba - perhydrobenz [e] indene were dissolved in 75 ml of 70% acetic acid and Heated to 60 ° for 45 minutes. The reaction mixture was cooled, poured into water and extracted twice with methylene chloride. The organic layers were washed neutral with 5% sodium bicarbonate solution and dried over sodium sulfate. Evaporation of the solvent gave 3a / S, 6/3 - dimethyl - 3/3 - (IR -1 - hydroxyethyl) - 7 - oxo-5a £, 9a / 9,9ba - perhydro - benz [e] indene. Melting point 110 to 110.5 ° (from ether-petroleum ether).

The 7,7-ethylenedioxy-3-oxo-3a (9,6 / 3-dimethyl-5a / S, 9a / S, 9ba-perhydrobenz [e] indene) used as starting material was obtained as follows:

A solution of 236 mg of 3ß - hydroxy - 3a / 3,6 - dimethyl - 7 - oxo - 2,3,3a, 4,5,7,8,9,9a / 3,9ba - decahydro-1H-benz [ e] indene in 40 ml of 95% strength ethanol and 5.25 ml of 2N sodium hydroxide solution was hydrogenated with one molar equivalent of hydrogen over 236 mg of prehydrogenated 5% rhodium-aluminum oxide catalyst. After the catalyst had been separated off, the solution was evaporated to dryness in vacuo and the residue was taken up in one liter of ether. The ethereal solution was washed with water, dried over sodium sulfate and evaporated to dryness in vacuo. The 3 & ß, 6ß- dimethyl- 3ß- hydroxy-7-0x0-5ass, 9a / 9,9ba-perhydro-benz [e] indene was obtained from the residue by crystallization. Melting point 144.5 to 145 °; [a] I ⁵ = -14 ° (c = 0.103 in chloroform).

A mixture of 10.45 g of the above compound, 50 ml of ethylene glycol, 1.5 g of p-toluenesulfonic acid monohydrate and 500 ml of benzene was refluxed overnight using a Dean-Stark adapter. The cooled reaction mixture was then treated with solid sodium bicarbonate until evolution of CO ₂ ceased, washed with 5% sodium bicarbonate and water and dried over sodium sulfate. After evaporation

609 608/31

of the solvent, crude 7,7-ethylenedioxy- 3 β -hydroxy-3a / 9,6 / 3-dimethyl- 5ass, 9a . A sample recrystallized from hexane had a melting point of 113.5 to 115 °. The crude ketal, which showed no carbonyl absorption in the IR spectrum, was used for the following reaction.

12 g of crude 7,7-ethylenedioxy-3/3-hydroxy- 3ass, 6β- dimethyl-5a / 3,9ass, 9ba-perhydro-benz [e] indene were dissolved in 500 ml of dry dimethylformamide. The solution was admixed in small portions with stirring with 12 g of chromium trioxide and then with a solution of 4 ml of concentrated sulfuric acid in 100 ml of dimethylformamide. The reaction mixture was stirred overnight at room temperature, then solid sodium bicarbonate was added and, after the evolution of CO _{2 had ended, it was} diluted with ether and washed with 5% strength sodium bicarbonate solution. The aqueous phase was then extracted one more time with ether, and the combined organic extracts were washed with 5% strength sodium bicarbonate solution and then three times with water. After drying and evaporation of the solvent, crude crystalline 7,7-ethylenedioxy- 3 & ßfiss -dimethyl-3-oxo-5ass, 9aj5,9ba-perhydrobenz [e] indene was obtained. Melting point after recrystallization from n-hexane 138 to 139 ° (flat panels).

Example 2

A solution of 6 g of 3a / I, 6a-dimethyl-7,7-ethylenedioxy - 3 - oxo - 5aa, 9a / ?, 9ba- perhydro -benz [e] indene in 200 ml of tetrahydrofuran was added to a solution of 118 mmol of ethylidene triphenylphosphorane in 200 ml Given dimethyl sulfoxide. The reaction mixture was stirred for 5 hours at 50 ° and then in ice water deterred. The reaction product was worked up by repeated extraction with petroleum ether of the extract and chromatography on an aluminum oxide column (activity level I) isolated.

4 g of the 3ass, 6a- dimethyl-7,7-ethylenedioxy-3-ethylidene-5aa, 9aj3,9ba-perhydro-benz [e] -indens obtained in this way were dissolved in 150 ml of dry tetrahydrofuran. The solution was treated with 16 ml of 1 molar BH ₃ solution in tetrahydrofuran under nitrogen with stirring. After 2 hours, 45 ml of 10% strength sodium hydroxide solution were carefully added, the reaction mixture was cooled to 0 ° and 20 ml of 30% strength hydroperoxide were added over the course of 25 minutes. After stirring for 1 hour at 0 °, water and ether were added, the ether phase was washed with sodium hydrogen sulfite solution and water and dried over sodium sulfate. Evaporation of the solvent gave 3a / 3,6a-dimethyl-7,7-ethylenedioxy-3 ^ - (IR-1-hydroxyethyl) -5aa, 9ass, 9ba-perhydro-benz [e] indene.

3.5 g of the obtained crude 3a.ß, 6a - dimethyl-7,7 - ethylenedioxy - 3/5 (1R - 1 - hydroxyethyl) - 5aa, 9aft 9bu - perhydro - benz [e] indene were in 200 ml of 80% iger acetic acid dissolved and heated to 60 ° for 75 minutes. The reaction mixture was cooled, poured into water and extracted twice with methylene chloride. The combined organic layers were washed neutral with 5% sodium bicarbonate solution and dried over sodium sulfate. After evaporation of the solvent, crude 3ass, 6a-dimethyl- 3ß - (IR - 1 - hydroxyethyl) - 7 - oxo - 5zLa, 9ass, 9ba - perhydrobenz [e] indene was obtained.

The 3ass, 6 "-dimethyl used as starting material - 7.7 - ethylenedioxy - 3 - oxo - 5aa, 9a / ^, 9b «- perhydro-benz [e] indene was obtained as follows:

A mixture of 10.45 g of 3ass, 6a-dimethyl-3ß-hydroxy - 7 - oxo - 5aa, 9a / 3,9ba - perhydro - benz [e] indene, 50 ml ethylene glycol, 1.5 g p-toluenesulfonic acid monohydrate and 500 ml of benzene were refluxed overnight using a Dean-Stark adapter heated. The cooled reaction mixture was

• treated with solid sodium bicarbonate until the evolution of CO ₂ ceases, washed with 50% sodium bicarbonate solution and water and dried over sodium sulfate. After evaporation of the solvent, crude 3aj3,6a-dimethyl-7,7-ethylenedioxy-3ß-hydroxy-5aa, 9a / ?, 9ba-perhydro-benz [e] - was obtained in the.

12 g of this compound were dissolved in 500 ml of dry dimethylformamide and then treated in small portions with stirring with 12 g of chromium trioxide and then with a solution of 4 ml of concentrated sulfuric acid in 100 ml of dimethylformamide. The reaction mixture was stirred at room temperature overnight. After adding solid sodium bicarbonate until the evolution of CO ₂ ceased, the reaction mixture was diluted with ether and washed with 5% sodium bicarbonate solution. The aqueous phase was extracted one more time with ether and the combined organic extracts were washed with 5% sodium bicarbonate solution and then three times with water. Working up the solution yielded 3a.ß, 6a - dimethyl - 7,7 - ethylenedioxy - 3 - oxo-5aa, 9a / 3,9ba-perhydrobenz [e] indene.

Example 3

3 g of cis -3-ethylidene-3a / i, 6 ^ -dimethyl-7,7-ethylenedioxy-5a / 3,9a /}, 9baperhydro Benzene indene were heated to 60 ° for 1 hour in 100 ml of 70% acetic acid. The reaction mixture was extracted with ether. Working up the extract yielded cis-3-ethylidene-3a / 3,6 / S - dimethyl - 7 - oxo - 5a / S, 9a / ?, 9ba - perhydrobenz [e] indene.

Example 4

2 g ice - 3 - ethylidene - 3a / S, 6/3 - dimethyl - 7 - oxo-5a / ?, 9a / 3,9bct - perhydro - benz [e] indene were used in. 150 ml of ether with the addition of 300 mg of lithium aluminum hydride Heated under reflux for 2 hours. The reaction mixture was then carefully saturated with Ammonium chloride solution was added and the ethereal layer was decanted. Evaporation of the Ether gave cis-3-ethylidene-3a ^, 6 / S-dimethyl-7f-ol-5a / S, 9a / S, 9ba-perhydro-benz [e] indene.

Example 5

To a solution of 4 g of cis-3-ethylidene-3a / ?, 6 / S-dimethyl- Ίξ- oil - 5a / S, 9a / 3,9ba-perhydro-benz [e] indene in 200 ml of tetrahydrofuran were added with stirring and nitrogen was added to 25 ml of an approximately 1 molar solution of borane in tetrahydrofuran. After stirring for 1 hour at room temperature, 50 ml of 10% sodium hydroxide solution were added dropwise. The reaction mixture was then cooled to 0 ° and 30 ml of 30% strength hydroperoxide were added over the course of 15 minutes with stirring. After one hour at 0 °, ether was added to the reaction mixture. The organic layer was separated off and on work-up gave 3ass, 6β- dimethyl-3 / 9- (IR-1-hydroxyethyl) -7 | -ol-5ass, 9a / ?, 9ba-perhydro-benz [e] indene.

Claims (2)

Patent claims: 1. Process for the preparation of 3- (l'-hydroxyethyl) -3a / 3-methyl-benz [e] indenes, characterized in that (a) a 3-oxo-3a £ -: methyl-benz [e] indene, in which other than the 3-position oxo groups in protected Form present, reacts with ethylidene triphenylphosphorane, if desired oxo-ίο present Splitting off protective groups, reducing oxo groups to hydroxyl groups and converting the latter to lower alkoxy or tetrahydropyranyloxy groups and (b) a 3-ethylidene-3a ^ -methyl-benz [e] indene thus obtained treated with a boron hydrogen and then with hydroperoxide. 2. 3-ethylidene - 3a / 3-methyl - perhydrobenz [e] indene the formula