DE1668602C - Process for the production of optically active 13 alkyl gona pen taenen - Google Patents

Description

HOOC

• λurin R and \ ■ iic '.or- -heiuleii Hedeumnyen

4. Modification of the method, 's j'eiiiai ¹ claim 1. characterized. dal3 Oas through condensation of the l.acton-sile. . <- (i -K-2 -X- 3s ί - Hydroxy - 4 '- cyclnpentenvl I - propinrr äuie with a 3-in-niedermnlekulai Alko \\ - plienylpropylniagnesiumhalogemd'.'ehildeii- reaction pr. '. duki in a single ; ien Stiiie is transferred by the discovery of a Cychsieningsagens m 3-nieilei molecular \ lko \ y - il - R - 17 - oxo - gona - 1..WiOtK. il-pentaen.

ni.inu irkLmyen aui Uiese \ erbindungen divide Ösirolic-in. *, 11ic in cheap! Way iiif the Biuilipoidüjiialt. '. irks

1 ■, i ^! hekann !. dall that from the menu chemist: eis üL'siiL'hie / ie! intestine face. a Syninesevert. '. h.en zu linden, the trot / eincseiis linear and' .etvuei.iiter Λ ι heM> j: iui! L · a C hai ak [ei bc-Vi. whereby, on the other hand, de ke:; ctions in the ue ^ ui ^ ehien direction run siereo- -.pe/iiisch, and d.il 'eniL ¹ \ i) r / e! tij.'e splitting. \ or / ug-way with a CiewinnungMTiciglic-hkeü des iiilIii ι; «unseen Uonieren allowed. Although ledoeh bcsUiiimie. Until recently, many syntheses have met one or the other of these requirements. are ueiiiue ^ 'experienced known who. at least partially, this I rfortlernisse L'leich / eitis! fulfill.

The procedure may be carefully determined several advantages and nnlerselieide! see about it up! due to a, very, uis-shaped commercial disease C'harak'.ei "I ai.s.JLlih-. Ii ·. One enters into this '»Experienced /« ei MoIeMiIe \ o ,, each of which does the rest de ·· kolilensUiifgeiuMes des (Ki.rons, whose Synthesis one in a het'ren / len an / aid from StLifeii durehlühri. X. weiterhh, offers the \ .oriie; jeude firlindune the possibility of na '.' h DuiLhftihi i.ng the first ilre. Levels which Aiifsp.iliirig 111 optically active isomers from / üfühier. and .A, ir a bcnachiik her Vi: ieil des Mirliesieiuiei'i \ erialire: "is imte; ·. lev-guild

of the undesired isomer by a change, which it transforms into a structure. 111 the the Siibs!; In / naturally inactive i-, 1. I in other W.rtjil read the present procedure is based on the laisache. then only a few serious reactions are required, which are also with Satisfying Aisleuten -'bygeliihri can graze

I ^! .is process / lit production of optically active! -V- \ | ky l-gona-peiitaene dei general lurmel

(legenstaiut.! ei Iriindung is a Veriahren to eisteilung of optically active 1 3- Alky I -.- -gona utaeuen the general I oinn'l

R-O

AA >

R ' -

where R is a C ₁ - to d-alkyl group and R "is a low molecular weight alkyl group and in positions I. 2 and or 4 there is a low molecular weight alkoxy group or a low molecular weight alkyl group and in the positions <i and / or 7 there is a low molecular weight alkyl group can is characterized in that 13 is a 2-R-cyclopentane-U-dione of the formula

orin R denotes a C ₁ - to C ₁₁ alkyl group and R denotes a leather molecular alkyl group and in which in the positions I. 2 and / or 4 a low molecular weight alkoxy group or a low molecular weight alkoxy group and in the positions 6 and / or 7 a low molecular weight alkyl group are present be able.

The l3 / <- R-Gon; i-i, 3.5 (IO) .K, 14-pentaene of all Formulas described in U.S. Patent 202 6! S6 have interesting Ilor-

in which R has the preceding meaning with a C 1 -C alkyl acrylate of the formula

ROOC-CH = CH ₂

wherein R 'is an alkyl radical having 1 to 6 carbon atoms means, condensed in an alkaline medium,

1 66δ 602

the obtained alkyl-3- (F-R-2 ', 5-dioxo-c> elopentyl | - propionate of the formula

R O

ROOC

Wherein R and R 'have the above meanings, reacts with a ketalizing agent that lent resulting alkyl-dl-3- (r-R-2'-X-5'-oxo-cyclopenlyl) -propionai the formula

ROOC

wherein R and R 'have the above meanings and X the Gru _h : e

O-13-R-17-X- ¹ ), 1U-secogona-1.3,5 i 10) .K (14> -tetraen of the formula

R X

■ -O

R "'O

wherein R, R "and X have the above meanings own, receives, the latter from the action of a cyclizing agent subject and the desired optically active 3-low molecular weight alkoxy-13-R-17-oxo-gonal, 3.5 (10), K.14-pentaene the general formula

(J

R-O

R "

where R "is a substituted or unsubstituted C ₂ - to Q-alkylene resi, saponified by means of an alkaline agent, the resulting dl-3- (1 -R-2-X-5'-oxo-cyclopentyI! -propionic acid of the formula

HOOC

wherein R and X are as defined above, in their optical antipodes with an optically active one Base splits up, the isolated optically active 3- (1'-R-2'-X-5'-oxo-cyclopentyl ! -propionic acid lactonized. the lactone of the corresponding optically active 3-11 '-R-2'-X-5'-H > v! roxy-4'-cvclopen th ν 1! -propionic acid der formula

R X

O-

wherein R and X have the above meanings with a 3- (m-low molecular weight AlkowphenyD-Propylmauncsiumhalogenid the formula

M siHal

R-O

wherein shark is a bromine. Means chlorine or iodine atom, kpndensie;., the condensation product of the action an alkaline agent unierwirl'i. the corresponding optically active. ^ - low molecular weight alkoxyin the R and R '"mean the above meaning ix ^ .l / en. isoheii

The dl - 3 - (F · R - 2 '- X - 5 - < ! \ e -. vclopeim i ι Pri'.pionic acid can hardly be used in neonibin. Cluniii. l-l.phedrm or the other lines mentioned opt in II Split active rabbits

Dk 'condensation de «. Facions Jet 3- (I'-R-2-Xi -Hvdroxy-4 -cyclopentene h-propioiv-acid k.mn aulkr the below mentioned 3-m-low-linear alkoxyphene> lprop \ lniagnesiuin-broni! ·.! ; \ v \ i with the corresponding -ehiond b / w. -ι -.! u! erfclgeii.

D: is 3- {m-low molecular; .i "Aiko>. \ T-phen \ lprop> I-magnesium halide can be converted into \ - and m \ c ·. /» - Siclhmg of the propylities by a liiedermoic alkaline residue and in the phenol nucleus by one or more low molecular weight alkoxy or low molecular weight alkyl radicals in 2, 4 and .or

[Jas procedure geiii.'iÜ sorüegendci Fii'mdurig. referring to the production of "id: ii": gen of the general formula IX be / iehi. i «.t summarized in ilen", attached scheme, worn, i1: e ■ · .schicdenen substituents which \ orgenanni ·. ·; ¹ ^ edeiitiingi ·! ' Ίχ ··

^ ν01 lying \ 'erdie dewiniuing de -

Fin considerable advantage

Leadership is based on the fact that e

during the splitting edialienei .. allows undesired isomers. Here / u uniei ^ irli man dioes isomers of the iinv.iil ung your v. üBrisjeii acid, which the cleavage in: ¹ > ler Keialt 111. '■ noi-, her \ or · calls and which by nature : \ u- ii; ahi \ L? {·. -K-? .5'-F) .- ο ..i-eyclopentvli-pr'ipionNiiure (VC 1 '..fr ·. Iiix-rliihn iliese then into the dl-3-ii -R-2 -X-' ι ι. n.> dopenn 11-propioiisäure (\) by I inw irL 11 η s. ¹ .i'.e- ke '.: iiv !. ^: - rimgsagL'iT- and ansciihchoiule l'eh.i: uiki'i. in watery alkali, around the intermedia! "iicoikk -! -! ^1. iviei of the carboxyl function / u \ erseifeii.

Hei this DuicIifuhriinL "!> I Hi. ·: W: - η ti da * present Procedure r, isbes> -nlere Juich followii ·. !!. Points are characterized:

(15 The Alkaliiii! De> Milieu-- / ur s. Ir ..! ', - iiNa: ion \ or ZR-Csclopenian-l .3-dmii mii .niiT ,. Alk ^ iacr \ kr wiiii diirch AiiHesenhcil i' ire- '-'i'iHi · \\ An.ui * ·. w ί.! ι i.illi \ Uiiinn. si' - 'schaflen

The KctalisicrungMiiJcH' ·. the ni; in mn an alkyl - 3 - (Γ - R - 2'S - dime - eyclopentyli-propiei-Kii converts, isl cm Alk \ lciu'l · - kcl or an Dimel.m

(O - CH, ~ CH, - O - CH,)

like methylethyldioxoliin in the presence of AlIn lciiglycol, and one works in the presence of an acidic catalyst, such as p-toluenesulphonic acid or methylsulphonic acid.

The saponification of the alkyl-dkV (l "-R-2'-X-.V-oxocyclopentyU-propionate is carried out using an alkali base such as caustic soda or potassium hydroxide.

The splitting of dl-3- (l'-R-2'-X-5'-oxo-cyclopentyl) propionic acid is made using an optically active base such as cinchonine. D () -Threo- (l-p-niirophenyl) - 2 - N, N - dimethyl - aminopropane-1,3-diol or 1-nor-adrenaline.

The Lactonisierungsagens is the anhydride of a low molecular weight aliphatic acid, such as acetic anhydride, we in the presence of a Alkalimetallsalzcs a low molecular weight aliphatic acid \ Natriumacelat.

The condensation of the actone of 3- (l'-R-2'-X-5 '- hydroxy - 4' - cyclopcntcrsy!) Propionic acid with a 3 - m - low molecular weight - alkoxyphenylpropylmagnesium halide, like -bromide, becomes in an ether. ' such as tetrahydrofuran, carried out and the subsequent alkaline treatment is carried out using a strong alkaline base such as methanolic Potassium hydroxide solution.

The cyclizing agent is a strong acid, such as a mineral acid such as sulfuric acid. Hydrochloric acid and phosphoric acid or a sulfonic acid.

The cyclizing agent is a mixture of phosphoric acid and phosphoric anhydride and the temperature is around 70 ^° C.

The invention also relates to a variant of the above process, in which the alkyl acrylate (II) is replaced by acrylonitrile. The condensation of this compound with the 2-R-cyclopentane-1,3-dione (I) in an alkaline medium leads to 3- (l'-R-2'.5-dioxocyclopentenyD-propionitrile, which is subjected to the action of a ketalizing agent, then saponified the dl-3- (1'-R-2'-X-5-oxo-cyclopentyl} propionitrile formed with a strong alkaline agent. receives the dl - 3 - (1 - R -2 - X - 5 '- Oxo - cycl. pentyl) propionic acid (V) and carries out the synthesis ■ as above ld

The gonapeniaen obtained by the process according to the invention can easily be converted into other steroid derivatives with interesting pharmacological properties, such as 19-nortestosterone or Ltyf-.Ä> h \ l-18.19-diiiortestosteron. be convicted.

In addition, and m modification of the process according to the invention, it should be noted that while this process is being carried out, the 3 (1 -R ~> -X-5-hydroxy-4'-cyclopentenyl! -Propionic acid with a 3-m-low molecular weight The reaction product formed by alkoxy-phenyl-propylnagnesium halide can be converted into 3-methoxy!

_20th

_30th

35

45

50

55

60

example 1

Production of left-handed 3- \ 1etho \ s -1 7-o \ oosira-l .3.5 (101.8.14-pentaen

Level Λ:

■ \ lh \ l - 3 - (I '- mellnl - 2 .5 - dioxo - eyclopentyl) pmpionate

In 125 ecm of anhydrous ethyl acetate leads one under a nitrogen atmosphere 50 g of 2-methyl-cyclopent.m-l.3-dione, 125 ecm of ethyl acetate, 240 cc of Atlnlacrylal and 118 ecm of a 20% triethylamine solution in ethyl acetate. The mixture is brought to reflux and held for 19 hours under reflux. It is concentrated to dryness under reduced pressure, then the residue is rectified and get 86.54g of ethyl 3- (r-methyl-2 ', 5'-dioxo-cyclopentyO-propionate, Bp 117 to 11Φ C at 0.55 mm Mercury.

The product obtained is a liquid with a refractive index #> f - 1.4685.

Analysis: C ,, H _le O, 212.24:

Calculated C 62.24. H 7.6 ° / ₀ .

deepening C 62.2, H 7.7%.

Level B:

Äthvl - dl - 3 - (Γ - methyl - 2.2 '- ethylenedioxy-5'-oxocyclopentyl ) -nropionate

In a mixture of 200 ecm benzene. 200 ecm Methylethyldioxolane and 3 ecm of ethylene glycol are added under a nitrogen atmosphere to 0.750 g of p-toluenesulfonic acid monohydrate, then 21.2 g of ethyl 3- (l'-methyl - 2'.5 '- dioxo - cyclopentyl) propionate, stirred 7 days at room temperature, add 1.2 ecm triethylamine to, removes the benzene by distillation, adds ethyl acetate, washes the obtained organic solution with a saturated aqueous sodium bicarbonate solution, then with an aqueous saturated sodium chloride solution and finally with water, dry and concentrate to dryness.

The residue is rectified under reduced pressure and 16.78 g of ethyl-dl-3- (l'-methyl - 2,2 '- ethylene - dioxy - 5' - oxo - cyclopentyl) propionate, Bp. 130 to 132 C at 0.15 mm mercury.

This product is a liquid with a refractive index ηζ -. 1.473.

Analysis: C ₁₃ H ₈₀ O ₅ = 256.29;

Calculated C oO.91, H 7.86%.

found C 61.0. H 7.6%.

As far as is known, this product is not described in the literature.

Level C:

dl - 3 - (Γ - methyl. - 2'.2 - ethylenedioxy - 5'-oxocyclopentyl) propicic acid

In a mixture of 48.5 ecm water and 30 ecm 12 g of ethyl-dl-3- (T methyl-2 .2 '- ethylenedioxy - 5' - oxo - cyclopentyU-propionate one. stirs 1 hour 45 minutes at room temperature, cools to 0 C and brings the pH of the reaction medium by adding an aqueous 10% potassium bisulfate solution to about 8, the aqueous extracted Phase with ethyl ether and remove the extracts.

309625/257

1 668

ίο

M.iii rrniit then ^ n pl'-Ucr! <Lr watery! I) SUHiI through / iiga '\ mi Kaiiunihisiilfat on 4.Π. salty! the milieu with sodium chloride, e \ tr;>. liieri with V. lnlaiher. unites the iM'akie people. washes the crhiilicnc solution with a saturated will. ':. .e: n Nali Hiiiichloridlösung. ιrtick: ict them and concentrate them / ur Trocl-.nc.

The residue and from a mixture of iso Propyl ether and petroleum ether crystallized and 8.85 g of dl-3- (r-methyl-2 ', 2'-ethylenedioxy-5'-oxocyclopentyl) propionic acid were obtained, F. - 66 "C.

I: .inc sample of this product is made by recrystallization from a mixture of isopropyl ether and petroleum ether purified, F. 66 C.

Analysis: C _n H ₁₁₁ O --- ₅ 228.24;

Calculated C 57.88. H 7.06 ° / ₀ .

found C 57.7. H 6.9 ° / ".

As far as is known, this product is not described in the literature.

Level D-

Splitting 1. with cinchonine

a) Formation of the right-handed salt of ctnchonine the 3- (l'-methyl ^ '. 2'-ethylenedioxy-5'-oxo-cyclo-

pen ty I! -propionic acid

11.6 g of cinehonine base are introduced into 1X0 ecm of ethanol one. stirs for 15 minutes at room temperature. then brings with stirring / to reflux and leads 10 c dl - 3 - (Γ - methyl - 2'.2 '- ethylenedioxy-5'-oxocyclopentylj-propionic acid cm. The mixture is stirred for H) minutes while maintaining the reflux, then removed 80 ecm of ethanol by distillation. The reaction mixture is brought to 20 ° C. and stirred for 1 hour this temperature, then lowers the temperature of the reaction calcium to a temperature / wipe 0 and 5 C and stir for 2 hours at this temperature. It is then left for 15 hours while maintaining stand at this temperature. The precipitate formed is separated off by filtration and washed him with cold ethanol and receives 15.4g of the raw d-cinchonine salts, [\] v · 119 (r 1 ° / ", ethanol), which is purified by recrystallization from ethanol. Is that how you get the right-rotating cinchoninsal? the 3- (I - methvl - 2.2 '- ethylenedioxy-5'-oxocyclopcntvl ! -propionic acid. F. 186 "C. f \] f. '

- t 127.5 ((l °; _0. methanol).

Circular dichroism: (ethanol) at 295 ηιμ. If ■ 1.25.

As far as is known, dices product is in the literature not described

h) Isolation of the d-3- (r-Mc;): yl-2 ', 2'-ethylenedioxy-5 -oxo-cyclopentyl! -propionic acid

5 g of dextrorotatory Cmchomnsal / der 3- (r-methyl-2 ', 2'-ethylcndiox \ -5 -oxo-cyclopentyl (propionic acid) are suspended in 25 ecm of water, then added dropwise ...- ¹ ut stirring 1.13 ecm of aqueous 10.7 n-ammonia solution / u. The mixture is stirred for 30 minutes at room temperature, the insolubles are removed by filtration, the filtrate obtained is saturated with sodium chloride and acidified to pH 4.0 with an aqueous potassium bisulphate solution. The aqueous phase is extracted with ether, the ethereal solutions become combined, the organic solution obtained is washed with a saturated aqueous sodium chloride-I · ·: iin :. imckiU't · ΐι:, uüi ti'ui i '' r / cnlncrl sie / ur I; -. K'k ne. i Vr K Ικ-'k .ι.μιΊ · λ "ίΙ dun. Ii crystallize • i'is ciiic Mi.iluii'L '-.'ι" I -lip: <i ■ v. I; i 'ner mnl lle \ ail;. \ iTiiiuM \\\\ (\ m.ii: -; \ Λ, λ- \ · I-3-1 I -Me \\\ I -V.?. -.t £ Ί> ijn -

■■ '..''I ■ i. I ",,. I" ϊ 111 \; 111Ί / irki.iardichr.iiMiiii · .: I Vhmoli Ivi 302 nvi. ι. 11.5s.

As far as is known, this product is <n de; Literature ίο not described

c! isolation and extraction of the unwanted

Isomers

The remaining cinchoninsal / e. those of the Splitting originate and by distillation of the crystallization liquor of the reverse acid corresponding diastreoisomers / ur dryness obtained are / are replaced and the crude free acid is separated as described in paragraph b) above is specified.

16 g of Cmchoninsal / e 7.5 g of raw acid, which is stirred for 15 minutes at 95 to 100 ° C. with 75 ecm of water and 19 ecm of 1N sulfuric acid included. You cool, vacuum and wash. Man thus receives the naturally inactive 3- (l'-methyl-2'.5 - dioxocyelopentyh - propionic acid. F- ". 1 Vi C. 9.2 g of the above building materials are treated, having a melting point of 126 ° C. for 135 hours at 20 ° C. with stirring mn HK) ecm methylethyldioxclane, 100 ecm anhydrous ncii / Aii. !, Γ'cv-iTi Athyicng'ykv ?! and 0.375 g p-Toiuo-sulfonic acid.

0.62 ecm of triethylamine is added, washed with water and distilled to dryness. The residue obtained is treated with vigorous stirring for 5 hours at 25 ("with 48 ecm water and 35 ecm 2N sodium hydroxide solution. The pH is brought _{to 8" by adding 10 "strength aqueous KHSO 1} (approx. 26ccr"), then extracted with of methylene chloride. The abgeirci.nte aqueous solution is mixed with 20 g of NaCl, cooled to 5 C and 3.5 by the addition of 10 ° / _n aqueous KHSO ₁ (about 38 cc) to pH to 4. The mixture is extracted with ether and distilled The residue crystallized from isopropyl ether and petroleum ether gives dl- (l'-methyl-2 ', 2'-ethylenedioxy - 5' - oxo - cyclopentyl) propionic acid, melting point 66 ° C., which is identical to the product obtained above is.

2. With D () - Three. - (I - ρ - nitrophenyl) -2-N, N-di-

methylaminopropane-1,3-diol

a) Production of the sal / es of D () -Threo- (l-p-nitrophenyl) - 2 - N.N - diinethylaminopropane - 1,3 - diols the right-turning 3 - (1 '- methyl - 2'.2 - ethylene

. dioxy-5-oxo-cyclopcntyl! -propionic acid 5 g of dl-3- (l -methyl-2 .2 - ethylenedioxy - 5 - oxo - cyclopenlyl) propionic acid one. adds 5.35 e Dt) -rhreo- (l-p-nitrophenyU-2-N.N-dirneth \ iamini> propane-1,3-diol (described in the French / Ovsthen patent specification 1 4SI 978) / u.

Stirred for 1 hour 45 minutes at room temperature, then left to stand at 5'T for 15 hours. One is drinking the precipitate formed, washes it with methanol and dries it. The crude product obtained becomes from Methanoi through criminalization purified, and 3.6 g of the sal / es des D () Threo - (1 - ρ - mtrophenyl) - 2 - N.N - dimethylaminopropane-1,3-diol are obtained the clockwise 3 (1- Mcthy! - 2, 2 '- äthylcndiosy - 5' - oxo - cycio-

11 12

pc: ι: M) -pr '<| T.'Hs; iiiu-. i. '-I ^'! \ |: Ι ¹ '. "Ι; ¹ Mlnkr.hcr.'. ''! ¹ UiI the annui'dic solution with

i '' · ■ '''', ι. Μν-ΐΙ'.ιΐιοΠ. ciiici 'A. ^: ÜM iucii Vi: 'i.; Mbicarhnnailösung. then mil

/!rkiilarudKoiMTv.'· .. on Aili.uvL, I. ■ ^ .47 W, issa! riniv ;; ti sic and concentrated sic to dryness.

Ki? 'I7 ιΐιμ. I) er Rik 'λ and is chromatographed on silica gel

Sowcil '"' Lkaniu.: ·! O: c-js Prodckl in the l.ilcralm f. Pliu-n and now cih.ill '.31 g linlvsdrehendcs I acton

flour described, the 3 - (! '■ Meilul - ?.'.?. ' - Aili \ lendio. \ y-5'-hydroxy-

, ..,. ..,, J cNclopcnijir., Ι. '. Ipuinviiiic. I '. 56 C, [\ Υή

hl / ci ^ cl / iinu dos Nai / c · - and <. lewiniuinü der iccnis' ,,, ■ ■ _t ! - ,,, ...

rotating V- (Γ - methyl - 2.2 - aihylemlmxy- Z.rkulardichrcsmus (ethanol): be. 229 ιημ,

5-oxo-L-yclopentyl! Propionic acid _{| 0} ^. 10 99

Iu a mixture of 10 ecm water and 0.4 ecm As far as is known, this product is in the literature

aqueous 10.7N ammonia solution leads to 2 g of the not described, Sal / es of the D () -l hreo-

(1 - ρ - nitrophenyl) - 2 - N.N - dimethylamino-propan-level F:

1.3-diol of the dextrorotatory 3- (l'-methyl-2'.2'-ethy- 15

lendioxy - 5 '- oxo - cyclopentyl) propionic acid. 3. Methoxy - 9 - oxo - 17.17 - ethylenedioxy ^ .lO-seco-

stirs for 1 hour at room temperature, sucks the un-östra-1.3,5 (10), 8 (14) -tetraen

soluble from. that from D () -Threo- (l-p-nnrophenyl) -. ,, Production of 3- (m-methoxyphenyl) -propyl-

2-N.N-dimethylamino-propane-l, 3-diol is made up of, washes away from the magnesium bromide

mn water, with 1 η sodium hydroxide solution, then with water 2 ° ^w

and this washing water is added to the resultant. In a dry container, the filtrate is passed under. The filtrate is added to 1.06 g of magnesium shavings with ethyl acetate in an inert atmosphere and a small iodine crystal to completely remove the remaining iodine crystal. The mixture is heated and extracted with the base. The aqueous filtrate is washed with sodium flame to / for sublimation of the iodine, is allowed to cool, and saturated Chlond by an aqueous potassium ² 5 a bisulfatlösung to pH leads then at 40 to 45 · C in about 30 minutes acidified 3.5 to 4.0 . A solution of 10 g of l-bromo-3- (m-methoxyphenyl) -proextracts the aqueous solution at pH 3.5 to 4.0 pan. dissolved in 40 ecm of tetrahydrofuran, a, after with ethyl acetate. The extracts are dried, after the reaction has previously been started by rapid concentration, washing with saturated nainuincmuride, adding a sufficient amount of the bromine solution, and then starting the derivative under reduced pressure. Stir for 2 hours and concentrate to dryness. receives a solution of 3- (m-methoxyphenyl) -propyl-

The residue is crystallized from isopropyl ether magnesium bromide with 0.42 mol / liter,

and one obtains 0.725 G clockwise 3- (1 -Mc-,. ,,,,,,

thvl - 2'.2 - ä.hylcndioxy ^ - 5 '- oxo - cycIopcntvM- ^h) condensation of the 3- (m-methox _yP heny!) - propyl-

propionic acid c. F. 70 to 71 C. [x] f, 9.3 35 magnes.umbrom.ds with the bee-turning lactone

(c U ⁰ / dioxin) of 3- (I - methyl - 2 .2 - alhylenedioxy O-hydroxy-

Circular dichroism (dioxane): h at 302 m, x _r 4-cyclo entenyl) -prop.onsäure

- ₍ 0.58. In 20 ecm of tetrahydrofuran one leads under inert

With the atmosphere described above, this product is 0.87 g of left-hand lactone

clockwise 3- (L- methy! - 2'.2 - äthylcndioxy- 4 ° 3 - (I '. methyl - 2'.2' - ethylenedioxy - 5 '- hydroxy-

5'-oxo-cyclopent> l) -propionic acid identical. 4 ^r -cyclopenteny1 ') -propionic acid; in. brings the tempe-

After concentrating to dryness the methanol temperature of the reaction medium to 55 ° C, then add table mother liquors from the production and the crystal dropwise 14.8 ecm of a 0.42N solution of dissolving the salt obtained under a) to get 3 - (m - M: thoxyphenyl) propylmagnesium bromide into the crude salt / des D () -Threo-1-p-nitrophenyl- ⁴⁵ tetrahydrofuran. stirs for 30 minutes at 55 "C, 2 - N, N - dimethylamino - propane - 1.3 - diol, which allows the temperature to rise to - 20 C in 25 minutes, 3 - (Γ - methyl - 2'.2 '- ethylenedioxy-, then holds 15 minutes hei 20 ^c C. Man S'-oxo-cyclopcntyU-propionic acid from which one the cooled to 55 C and add 10 cc produces a saturated levorotatory acid to a working aqueous Ammoniurmulfatlösung and 50 cc Äthei example analrg The ethereal phase is used to obtain the right-turning ^ ⁰ / u. The ethereal phase is separated by means of decanoic acid, it is washed in water, the aqueous phase is extracted

The levorotatory acid melts at 70 to 71 Γ phases with benzene. \ cleans the organic phases

and its ability to rotate is 9.3 (r - 1.1 ",,,. washes > ie with a saturated aqueous sodium

Dioxane). It can be done in a manner analogous to pre-chloride solution. dries and concentrates to dryness

are described above, racemized. ⁵⁵ 2.17 g of product are obtained.

Stage E: c) Alkaline treatment

Left-rotating lactone of 3- (L-methyl-2 ', 2'-ethylene- \ _{n e} j _ne mixture of 22 ecm 1.3f) n-methanolic-

dioxy- V -hydroxy- 4 '- cyclopentenyl) - propionic acid potassium hydroxide solution and 1.5 ecm of water are added 2.17;

The product obtained under b) is introduced into 97 ecm of acetic anhydride under nitrogen and brought

Substance atmosphere 0.078 g anhydrous sodium acetate. to the reflux. One sets the heat up ',' * hour

then 6.5 g dextrorotatory 3- (L-methyl-2'.2'-ethylene- on, then cools, adds Fis to '.ind bring the pl-

dioxy - 5'oxo - cyclopentyl) propionic acid. Man by adding acetic acid to 8. Man extra.liei

bring the reaction mixture to reflux and keep the reflux for 20 hours with ethyl acetate

the at. Is added 20 cc of acetic anhydride to be distilled ⁵ the extracts are washed with a saturated aqueous

then slowly under normal pressure until sodium chloride is dissolved, dried and evaporated

X) ecm Destiiiai has received. It is concentrated under dryness. The residue is replaced by Chrotnatc

reduced pressure / ur dryness, dissolve the residue graphic purified on silica gel and one obtains 0.56

} - Mclhoxy - 9 - oxo - 17.17 - iithvlontlitixy- ¹ · '. 10-sccoöslra-l.3.5 (10l, 8 (l4) -ieiracii.

UV spectrum (ethanol): Max 2> 2 ιημ. ι 7 ') 4Ο. As far as is known, this process is not described in the I iteralui.

Level Ci:

Methyl ether des 8. ¹ U 4.1

Iiis-dehvdro-oestrons

In a mixture of 6 g Phosphorsäurcanhydrid IO and 8 cc of 85 g ° / _o phosphoric acid is carried out at room temperature and under inert atmosphere, 0.520 g of 3-methoxy-9-oxo-17:17-äthyiendioxy-9,10-seco-estra-l, 3.5 (10) .8 (14) -letraene (optically active), then stirred for 30 minutes at 75 ° C. The reaction mixture is cooled and ice is added. stir for 10 minutes. then extracted with ethyl acetate. The organic extraction solutions are combined, the organic solution obtained is washed with an aqueous sodium bicarbonate solution, then with water. dry them and concentrate to dryness.

The residue is chromatographed on a layer of silica gel and the levorotatory 3-methoxy-17-oxo-oestra-1.3.5 (10) .8.14-pentaene is obtained. F. - 142 C. [x] f - 100 U - 0.5%, chloroform (or methyl ether of 8.9.14,15-bis-dehydroestrone).

Example 2

Preparation of the dl - 3 - (Γ - methyl - 2 ', 2' - ethylenedioxy-S'-oxo-cyclopentyD-propionic aire by condensation of 2-methyl-cyclopentane-1,3-dione with acrylonitrile

Level A:

3 - (Γ - methyl - 2 ', 5' - dioxo - cyclopentyl) - propionitrile

The mixture is heated 20g 2-methyl-cyclopentane-l, 3-dione in 100 cc of ethyl acetate, the / 10 ° includes ₀ triethylamine and 58.5 cc of acrylonitrile about 64 hours with reflux. The solvents and excess reactants are evaporated in vacuo. The remaining oil is distilled at 0.2 to 0.3 mm. 22 g of 3- (l'-methyl-2 ', 5'-dioxo-cyclopentyl) propionitrile are obtained. which passes at 136 to 140'C.

Analysis: (, H ₁₁ O ₄ N 165.19:

Calculated C 65.43. H 6.71, N 8.48 ° / ₀ .

found C 65.2. H 6.7. N 8.4 ° / ".

35

⁴⁵

Level B:

dl - 3 - (1 - methyl - 2 ', 2' - ethylenedioxy - 5 '- oxocyclopentyD-propionitrile

5 g of 3- (l'-methyl-2 ', 5'-dmxo-cyclopentyl) propionitrile are stirred in 50 ecm of methylethyldioxolane containing 2 ° / ,, ethylene glycol and 1 g of p-toluenesilfonic acid. 9 hours at 20 ° C. 2 ecm of triethylamine are added. diluted with water, extracted with methylene chloride, washed with water and distilled to dryness. 6.5 g of dl - 3 - (V - methyl - 2.2-ethylenedioxy - 5 '- oxo - cyclopentyl) - propionitrile are obtained.

As far as is known, this product is not described in the literature.

Level C:

dl - 3 - (Γ - methyl - 2,2 '- ethylenedioxy - 5' - oxo- _6s cyclopentyl (-propionic acid

1 ecm of ethylene glycol is heated. 2 ecm water and 0.5 ecm potassium hydroxide solution (of 700 g / liter) with 0.3 g dl - 3 (I '- Meihyl - 2 .2 - alh \ iendio \> · ^c ' - oxo-1. ". 1.1 (IpJiHyI) -IIrUpI (IInInI with stirring for 15 minutes at 100 to 110 C. One cools and extracts with N ¹ CiInlenchlond. then mil lssig-.äure; ithvlesiei exirahicri. The organic / er ΊπκΛικ · brought! xi; .ikt lielert dl - 3 - (1 - Mellnl - 2 .2 '■ äthvlen - dioxv - 5' - o.xocyclüpentyl) -propionsänrc which is identical to the product obtained in the previous example.

Example 3

Manufacture of 3 - methoxy - 13 /? - ethyl-17-oxogona-1,3.5 ( 10) 8,14-pentaen

Level A:

Ethyl - 3 - (Γ - ethyl - 2'.5 '- dioxo - cyclopentyl) propional

In a mixture of 1000 ecm of ethyl acrylate and 1000 ecm of ethyl acetate with 10% triethylamine are introduced into 200 g of 2-ethyl-cyclopinlan-1,3-dione. The reaction mixture is brought under a nitrogen atmosphere / under reflux and the reflux is maintained 2i hours at. The resulting solution is concentrated to dryness under reduced pressure. the The residue is rectified in vacuo.

321 g of ethyl 3- (l'-ethyl-2 ', 5'-dioxocyclopentyl) propionate, boiling point - 126 ° C. at 0.5 mm mercury, nf 1.4700 are obtained.

As far as is known, this connection is in the I. > ature not described.

Level B:

Ethyl - dl - 3 - (Γ - ethyl - 2 ', 2' ■ äthy1endioxy-5'-oxocyclopentyO-propionate

In a mixture of 2000 ecm of methylene chloride. 2000 ecm of methylethyldioxolane and 50 ecm of ethylene glycol are introduced into 6 g of p-toluenesulphonic acid and 20r ε ethyl - 3 - (Γ - ethyl - 2 ', 5' - dioxo - cyclopcnt) ¹ ) propionate. Bring the Rca ¹ '^;Onsmischui; t under a nitrogen atmosphere to reflux, the condensate being returned through a column with dewatering material, such as an alkaline aluminum silica. The reflux is maintained for 12 days, renewing the dehydrating agent and dividing the reaction medium into 3 dividers. 1.5 g of p-Toliu sulfonic acid and 10 g of ethyl glycine> 1 are introduced. M> cools down. make alkaline with triethylamine, wash the organic solution with a saturated aqueous sodium bicarbonate solution, then with water. The aqueous extracts are combined, extracted with methylene chloride, and this methylene chloride extract is added to the main organic solution. dries the organic solution obtained, concentrates it to dryness under reduced pressure and receives 248.4 g of crude Ath \ l 3 - (Γ - ethyl - 2,? - ethylenedioxy - 5 - oxo - cycio pentyU-propionate (product A), which as such to obtain the free acid use: will.

A sample of this product is rectified under reduced pressure, b.p. 160 ° C. at 25 mm square silver, nf 1.4790.

As far as is known, this connection is in the I ite rature not described.

1

Siule (.

dl - 3 - (i - ethyl - '' ■. "'- al hyleiu! ui \> - ^s - i' \ icyelopcniy I (-propionic acid

In 1430 ECM -.äßrige 2 η ■ Naironlauuelosung lührt _s one 24S.4 g of the product obtained sorsiehend \ em and stirred uc Reakuonsniischung 3 hours at room temperature. One cools ii..s Reaktioiismediuiii iuif ^c C ΐί \ - · ί \ l-.rmgi semen pll by adding an aqueous k.'In'mhisulla'.li-solution to '' .O. The _{aqueous alkaline solution is extracted with} inert water. sgendi vie mn Nairn mehlorid, its temperature depends on aiii ■ ■> C and adjusts its pH to 4.0 by adding an aqueous potassium disulfate solution. The aqueous acidic solution is extracted by setting the pIl to 4.0 after every extraction. The essential extracts are saturated with an aqueous one. · !! Nalriumchloridlostmg gcssas' .- hen. then dried, decolorized with animal charcoal and con / heated under reduced pressure / urine. The back, ₀ standing is crystallized from Isopropyläiher and obtained in / SSEI batches I t Sf- g of 3- (i -. \ Ihyl-2 .2 -äths lendiov.ö -oxo-cyclo penis h-pronionsäure '7i>

up to 77 Γ.

Line l'rohe of this product is derived from Kopropsl, j more critical. I. 7 "(

By \ tiflose m / ssigsäureäthslesier uul \ adding 2.> Dipht: nyl-piper.i / in one gets the 2.5-Diphenylpipera / insal / der 3-1 1 - Vlliy 1-2 .2-älhs lendioxs -:> - oxo - cyclopeniyl) propionic acid. L.! 42 C. whose Sucksioffweri 3.S g "" g i'Iheorie: 3.S2) is.

As far as is known, this connection is in the literature r. not described

Level D: - ^

Splitting up

a) Formation and isolation of the sal / es of the beekeeper Nor-adrenaline base and eggs turning 3 - (L - ethyl - 2'.2 '- äthslendioxs - 5' - oxo - cyclopeniyl (-propionic acid

20 g of dl-3- (! -Aihsi-2.2-ethylenedioxy-5'-oxo eyclopentyl) -pri pionic acid and 14 g of left-rotating 2-aliino- i (V.4'-dihydro.xyphenyl) ethanol were poured into a mixture. With 30 ecm of hot water, the reaction mixture increases while stirring in a water basin, removes small remaining insoluble fractions by nitration, inoculated by scratching. preserved 4X hours at 0 (under lichiausschliiß on. isolieri by suction i. \ ^ n precipitate formed, it teigt with a ssäßrigen Nainumchloridlosuiig and iroekiiJt it at rcdu / iertem pressure. This Rohproduk 'is risiallisieren by triple aufeiiKMulerl'olgendes I ιιλ. 111 ^ of an aqueous sodium chloride solution, and 5s one crlliiil ^l ', 4g of the sal / es of the left-turning noradrenal hare iv.with the right-hand 3- (l-aihyl- 2'.? '- aihylendioxy - S' - o.xo - cyclopeniyl) - propionic acid ^l; 1X4 C. [\\ r 20 (· "" water)..!..

I-.mc sample of this product is crystallized from water fo l \ 1S5 C.

Circular dichroism (in ethanol): \ r at 2XX to 2W nvx '0.34.

As far as is known, this compound is not described in the literature. ^(l 5

By saturating the crystallization pulp liquor of the crude product with sodium chloride, alkaline mixtures with ammonia. Vacuum then wash 602

of the precipitate formed one wins the bee-turning end Nor-aiirenalin phase. L. 242 C (kofier).

b) Isolation of the re-rotatory 3- (I-ethyl-2'.2-riih> lenuui \\ - 5 -oxo-cyelnpentN 11-propionic acid

4. T> X g of the salt of imksdrelilid noradrenalinase and animal reelus-rotating 3- (1 \ th \ l-2 .2 ätlnlendioxv-5-oxo-c \ clopeniyl) -propionic acid are introduced into 14.1 ecm of water . L. 1S4 <. em. The mixture is stirred for 30 minutes at room temperature without exclusion. Cool them down inside the Siicksioffaimosphere to ■ 5 (. iirinui the pll of the N'ilieus by adding an aqueous ammonia solution mn 22 Re on K'.O.N ¹ .m stir:, then let the smnd stand at 0 C ', isolate through Suck off the formed precipitate, washes ij-, ϋ with an \ etdiuinlti, aqueous ammoinakl (> siinü. Then with W -'s ^ er iipü irocknei him. You get s _t · ϊ.

Da- I -iltrai and some washing water are saturated with natural chloride and slici.sUiffalniosphere. One cools el ts Reaklioiismednmi aiii 5 (. Bring his pll-Wen d'irch progressive draws of an aqueous potassium biscuit liquor to 3Λ I see in low-temperature liquid If the sodium chloride solution is added, dries them, con / enirieri them uniei reduced pressure and rock under Mr.ksioll / ur I. You get 2. (0 g right-handed 3- (I ■ ΛΐίηΙ-2'.2 - ethylene dioxy - 5 - oxo - c \ clopent_ \ l) - propionic acid. [\] 4. ¹ ) ti i ",,. dioxane).

Zirkiilardic'hrv> ismu »(Dio \ j ''. L: I» hei 2XX his 2'K) IiVi 0.11.

Well known. ι> ι this invention in the Iieraiur flour described.

el isolation of the levorotatory .V (I -ethyl-2'.2'-ailnleiuhoxy-s -o \ o-cyclopeiit> I; -propionic acid

By H iiNsirkening \ on Yohimbin on d 1-3-1 Γ-Λ ι h \! - 2.2 '- älh> lendioxy -> - oxo - c \ elopent> I) - propionic acid you get the N 0l11mb1ns.il/ iler left-rotating 3 - (I - ethyl - 2 .2 - ethylenedio \\ - 5 - oxo - cyclopent \ l) propionic acid. which is purified by crystallization from ethanol. I. I'M C

Circular dichroism t dioxane 1: I / 2S5 mv 1.4.

Ii 270 mv 1.7.

As far as is known, this N'erhmdimg is in the I iteraiur not described.

Starting from son deili Yolnmhinsal / set / l man die anti-clockwise acid free and clean! it in an analogous way, as / ur ι res \ i "iiimg of the right-turning acid, starting with the nor-adrenaline / and man This is how the left-rotating 3- (L- \ thyl-2'.2'-ethylenedioxy-5'-oxo-csciopenis is obtained I (-propionic acid. [S], ■ '5

ti 1 "". dioxane).

Circular dichroism (Dio.xan): Ii at 296 mμ 0.10.

So far known, this connection is in the literature flour described.

Sink

Left-turning I acton of the rice-turning 3 - (L - ethyl - 2 .2 - äthvlendioxv - 5 '- hydroxy -

ey el ο pe η t en y i-4 -) - pro pi ο η acid

5 In 34 ecm acetic anhydride one leads under meriei

Atmosphere 20 mg \ 'a: numav.eiai and 1.53 ti rechisrotating (in dioxane) d-3- (1 -AtIn l-2'.2'-äihy lendioxy 5 -oxo-cyclopentyD-propionsäuic. Bring in the reaction initiation to reflux and concentrated under inert atmosphere, very slow in the manner that about Hälf'.e of Accianhydnds is entfeint in about 15 hours is cooled Fuei;.. i benzene and 0.10 cc of pyridine / u the Reakiionsmedmm. Concentrated to dryness under reduced pressure and under an inert atmosphere. The residue is treated with M el In cyclohexane. The mixture is concentrated under the same conditions as above for drying, and the procedure is repeated several successive times backlog is dissolved in Ainet mixture of Benzcl and Vihc The organic solution is 1 with a;.. washed aqueous Nainumhicarbonatlosung then mn water they are dried and concentrated them to Iroekne The residue is purified on Sihcagel graphic Chrumaio- by ₂ ^ and man. receives i.27g raw Corresponding I acton of the clockwise 1 - 3 - (1 '- Ethvi - 2 .2 - älhyleiidioxy - 5 - hydroxytyelopentenyI-4 1-propioiic acid. | \] IH). 5

(r 1 "". dioxane).

7 Illuminated dichroism (ethanol).

I »12.1 at 227 m _{; i} .

I. 0.42 at 305 nvi.

As far as is known, this connection is in the I iteralur flour described.

Level L:

3 - methoxy - ^c > - oxo - 'V - äthyi - 17.17 - äthylendioxy - ^l ) .l0 - scco - gona - 1.3.5 (10) .S (14) - tetraen al production of the 3- (m - methoxy - pheny l) -prop \ i

magnesiuinbriimids

1.06g of magnesium shavings are placed in a dry container under an inert atmosphere a small crystal of iodine. One heats with the 45, I lamb until the iodine sublimates, lets it cool down, then performs at 40 to 45 C in about 30 minutes solution of 10 g of I -Bromo-3- (m-melhoxy-pheuy I (-propane, dissolved in 40 ecm I eirahy drofuran. one. after checking the reaction by quickly guiding it a slight liking for the solution of the Bromdenval started shark. The mixture is stirred for 2 hours and a solution of 3- (m-methoxyphenyl) propylmagnesium bromide is obtained of 0.42 moles I iu: r.

b) Condensation of the 3- (m-metho \ y-pheny l) -propy I-magnesium chromide with the levorotatory l.actone of the 3 ■ (Γ - ethyl - 2 .2 ' - a'ihylend; o \ y - 5' - Ailmxs-

4'-cyclopenienyh-propionic acid

In 24 ecm tetrahydrofuran one leads under inert Atmosphere 1.04 g of levorotatory lactime of the dextrorotatory 3 - (L - ethyl - 2 .2 '- älhy iendkuy-.V-Indroxv-4'-cyelopentenyI! -Propionic acid one. brings the temperature of the reaction mixture to 55 C. Adds then dropwise at 17 th ecm of a 0.42 n-3- (m-methoxy-plienyi) -propylmagtiesiumhromidlösung in tetrahydrofuran too. stirs at 55 ° C. for 30 minutes Adjust the temperature to 20 Γ in 25 minutes.

40 hiih then 15 minutes, at 20 C. One cools _{: left:} | ss C and fiisit 12 ecm aqueous saturated AmmnnH.!> isiiifallö., and MUvm Äthviälher zu Ma-. calls the ethereal Ph: '. se by decanting .ti ·. Wash mc with water, euraiuE the aqueous phasers nut Beivol. unites the organic phases. What.- | \ t you in an external, saturated nairium, hlond solution, irod.nei and concentrated to dryness.

c) Alkaline treatment

The kiickstand tin obtained under b) is introduced into a mixture of 26.4 ecm 1.36 n-niethan, pretty Kalijau-e and 1 sccm of water and brought to:,. Riicktlul.V You put the I rhilzen during 'Λ · nui. foil, then cools, adds 1 is and brings the pit-Wer: to ¹ ^ by adding acetic acid. Man exlrahiei; the reaction mixture with V ssigv; hne; Uh> le-.lv :! washes the tracts with a long stem: · Viirnimehloridlosiiiii-. dry and steamed zn: "Iroekne. Dc: Kucksiaiid is cleaned by Cliromaiisirap'iiie on Siücagel and you get da.-opu-ch active 3- \ K lh .. v \ - ^l ) -nxo-l .y-äihvl -1 7.1 7-iiihvleiidinxy- ^l '.lii-seco-gona-'l.3.5 (ll)), X (141-ieiraen.

As far as known, in this product in the I Heran: not described

SiuiV

- Meihow - i:

üthyl - 17 - oxo - gona - 1.3.5 (! (ii. P.14-pentaen

In S.4 a mixture of HIg Phosphorsäuieanhydrid and X ecm .V ""g; ger phosphoric leads nv'.n u opiisch at Ratmitemperalur and under inert atmosphere O.72S active 3-Metho \ y ^l '-o \ o- 13 ..;! - älhyl - 17:17 - ethylenedioxy - ⁽ '.'O - seco - guna- .5.5 (divides Km.K (14) -ietraen then stirred for 30 minutes at ⁷ 5 C. the mixture is cooled, the reaction mixture, added. The organic reaction solutions are combined and the resulting organic solution is washed with an aqueous sodium bicarbonate solution, then with water, dried and concentrated to dryness.

The Rüeks'and is on a silica gel layer Chromatographs and you get the optically active 3 - methoxy - 13 / i - ethyl - 17 - oxo - gona ! 3.5 (i0) .; s. 14-pcntan.

As far as is known, this connection is in the 1 Hera! ur not described.

Example 4
3 - Meihoxy - 7 \ - methyl - 17 - oxo - ösi / a - 1.3.5 (Hi).

Level A:
Manufacture of the magnesia connection

To 320 mg magnesium flakes are added at 25 ° C under an argon atmosphere for a period of 30 minutes a solution of 3 g of 1-bromo-2> -methvl-3- (m-mclhoxyphenyl) propane [λ] ;? 35 (r 1 "",

Ethanol) in 14 ecm I etrahydrofiiran. One stirs 2 hours and receives a solution of 2 \ -Methyl-3- (ni-meihoxyphenyl) -propylmagnesiumbroniii.l of 0.5 mole liter.

Level H:

Condensation of the 2 \ - M et Iv. I - 3 - (in - methoxyfihenyll-propylnuignesiumbromids with the levorotatory l.aeion of the 3 - (1 - methyl - 2 .2-ethelendioxy o - hydroxy - 4 '- cyclopentene I) - propionic acid / u 970 mg de * levorotatory I.actons of

3 - (Γ - methyl - 2'.2 '- äthylendkm - 5' - hydmxy-

4 -eyclopentenyh-propionic acid (obtained in stage 1 in Example I, dissolved in 12 ecm tetrahydrofuran and 3 ecm toluene, 14 ecm of the magnesium solution obtained in stage Λ is added at 70 ° C. for 30 minutes 3 hours with stirring at 70 ° C. then brings it to 2 ° C. and maintains this temperature for 1 hour 30 minutes. It is cooled to M) C. and excess magnesium compound is destroyed by adding Animomumsulf! ". It is extracted with ether and purified glass CH obtained by chromatography on silica gel, giving 200 mg of 3-Meihoxy-7 \ -ineth \ l- ^l - '. 14-dio \ o-17-ethyiendioxy- ¹ JJO-X.14-diseco-östra-1.3.5 (H)) - Irien.

I R-Spekirum:
Absorptions at

liV-Spekirum:

! 73 (Km 'and 1710cm

CH,

HC

COOR '
(Π)

(I)

R'OOC

HOOC

K160 hei 21 S im.
ι 21X0 at 272 to 273 ηιμ.
ι 145O at 274 to 2X0 ηιμ.

Si lic C:
C; clisii "img

To 50 mg of the product obtained in Step U adds to kon 0.5 cc / entnerie sulfuric acid (66 Be): one ruh π 1 hour TiPd gielit in a \\ 'ater / l: is Natriumbicarhonat mixture. It is washed with water and evaporated in a vacuum / ur dryness cm. 34 mg of 3-methoxy-7-methyl-17-oxoö.stra-1.3.5 (H)). 8,14-peiitaen are obtained.

UV spectrum: absorption at 314 ηιμ.

Starting from 1 - bromine - 2 / i - methyi-3- (m-: nct!> oxyphenyl) propane. [\]; - 35 (r 1 ",,., \ Thanoi)

3-methoxy-7 /> '- melhy'-17-oxo-i'istra-1 is obtained in the same way .3,5 (10) .X.14-pentaen.

3 °

35 HOOC VC

R.
C) -

HOOC

40

45 VA

VB

R '"O

MgHaI

VIl

VI

55

60

65

R "'O

(in the VIII

21

R O

R O

R '"O

IX

R "'O

Claims (3)

668 claims: 1. Process for the production of optically active Π-Alkslyona-peniaencn of the general formula: R ■■■ () worm R a (., - to C .-- \ lkyl resi and K a _t < ! iietlernuilekui.ircp. \! k;. | ies! mean and in which veh · ■; Jeii SicUun-jcii '... "! and or 4 tvi nicdcrtiiiilck ι; - Ji "et" .- \ lki '\\ rol or a: .iedeimolck>.ilare; AH. vir-jsl ui; J; n the positions (ι and or
a low molecular weight \ lk \ li'est belinden koni.cn. v, dadu ι e I ": Li eke η η / e ι eh η e;. daIi one a 2-Rt \ i i.ipe'iian-i .3-dii in the I ormei saponified by means of an alkaline agent, the obtained dl-3-ί I '-R-2'-X-5' - (.) xi'-c \ c! (ipenl \ li -prüpn.insäiir? the formula KOOC worm K and X have the preceding meaning
sit / eii. into their optical antipodes mn e
optically active base splits the isolated op:
active 3-d'-R-2 -. "'.- S-Oxo-cyclopentvli-pr, r
acidic lactonized. the l.actone of the cnisp'ec'i; .- optically active 3-i I'-R-2'-X-5'-Hviru \> -: _v
pentenyl propionic acid from lormei _■: - · .- _> have .., with a 3-in-niedeimolekular: wherein R and X di ·: above Beuc i iii.. ph.en \ i props I ma gne-ium halogen κ; dei I ο: never; «Υ ;;: ', R the \ (<i bedouUing besii / i. Mn one ('., - hi% ("', -. Mkyiaerylal dei lOrmel R OOC I. Il CII ... where R is an alkyl radical with! hi ^ 6 carbon atoms means condensation in an alkaline environment. the obtained Aik \ l-3-ii -R-2 '.5 -dio \ o-c> clopeniyll-propionate > ier lorniel R O R'OOC wherein R and R 'have the above meanings, reacts with a ketalization agent, the resulting alkyl-dl-Xl'-R-Z'-X-S'-oxocvclopenlyll propionate the formula ROQC wherein R and R 'have the above meanings and X is the group 55 P ' C) denotes in which II "represents a substituted or unsubstituted C ₂ - to Q-alkyl radical. RO wherein shark is a bromine. Means chlorine or iodine atom, condensed, the condensation product of F. subjected to the action of an alkaline agent, the corresponding optically active 3-lower diol kular alkoxy-9-oxo-1 3-R-1? -X-9.1 () - secogonal.3.5 (ll)), 8 (14l-teiraen the formula R "O wherein R. R "and X have the above meanings, the latter is given the action of one Subjects cyclization agent and the desired optically active 3-low molecular weight alkoxy-13-R-17-oxo-gonu-1.3.5 (10) .8.14-nentaene the general formula R O R '"O in which R and R have the above meaning, isolated. 2. Modification of the method according to claim I, characterized in that one 2-R-Cyclopentane-1,3-dione with acrylonitrile in al- fcaiischen Mihei! koiidf as.ei t. L- 3 (j R .;. ■ · Dio \.; - t vi.:lo|-iei:. \! I- propionn!: L keiali-ieii. Das -ich ei -'1 -! - L- IIlIe di 3 - II -I ·· 2 X ^; - (Kn - -.V Jn-JP ^ ii'v!) -; ir Τί mini ii.il ein siaiki'i .dkaii-chen A-.ieiis vei- .eiPi. die di -'- ι i -H. '■ X - ^ - <>>. o-cy ciopeii- * "t \ I i-proi'-ii'-isai'iL- eihall n: iJ du Synthesis as ί: ι \ 1isjTLiJ1, indicated. Inr'.sel / t. »Ni'u R liii.i X die -» ο; standing Hedeiitungen hesit / ei: 3 procedure i..i AiispniJi 1 or 2. thereby ■ fekenn.-calibrated. dall mm wcileihiii di- iIIlii! i ^f! Few unshaken, optically active IscMiiere of } - \\ - \ ^f 1 - X - 5 - ι Ko - cyclopentyli - propionic acid. V. null K inn. · \ The introducing Hedeutiingeii | iesi [/ en. L'cwinir .. by peeking out the kei.ilfimkluui inn Liner AäiUigen acid and. which is' 5 tv-i / bcmk- ^x -i \ K 2 .S ihov.i - c \ c-.ipeni.ylll'i'-j'ions ".,; e ciurJi I ιιιλ ii ki: ng one k "!: iusie-: uiuis.igen- in di-3- <i -R-2-X r 'Kd-cycinpn.- ·. ! ',! · -; <rnpi.! Iis; iii: e üherfidirt. .iiisJiheBciu! mii ■. ·. . ·.! '■! Igen).-X'k.ihnieiaiihvdro. ·. d treats .liai die - ° :: ewu η sch te dl '1 ■: ■ - ·' .- 2 '■ \ - ^ (K "._ .. -jn: - :.'i'.i \ I ip, !!! Hüiisjiiiv d-. l-oiinei