US2734066A - Method for the preparation of dfflydro- - Google Patents
Method for the preparation of dfflydro- Download PDFInfo
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- US2734066A US2734066A US2734066DA US2734066A US 2734066 A US2734066 A US 2734066A US 2734066D A US2734066D A US 2734066DA US 2734066 A US2734066 A US 2734066A
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- US
- United States
- Prior art keywords
- dihydrotestosterone
- androstan
- acid
- cyan
- boiling
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
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- 238000002360 preparation method Methods 0.000 title claims description 10
- NVKAWKQGWWIWPM-ABEVXSGRSA-N 17-β-hydroxy-5-α-Androstan-3-one Chemical compound C1C(=O)CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@H]21 NVKAWKQGWWIWPM-ABEVXSGRSA-N 0.000 claims description 34
- 238000000034 method Methods 0.000 claims description 24
- 239000003795 chemical substances by application Substances 0.000 claims description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 22
- 239000002253 acid Substances 0.000 claims description 16
- 238000009835 boiling Methods 0.000 claims description 16
- KRVSOGSZCMJSLX-UHFFFAOYSA-L Chromic acid Chemical compound O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 claims description 8
- 230000001476 alcoholic Effects 0.000 claims description 8
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 8
- 239000011707 mineral Substances 0.000 claims description 8
- 239000003377 acid catalyst Substances 0.000 claims description 6
- 150000001298 alcohols Chemical class 0.000 claims description 6
- 229910052783 alkali metal Inorganic materials 0.000 claims description 6
- 150000001340 alkali metals Chemical class 0.000 claims description 6
- 238000007865 diluting Methods 0.000 claims description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 6
- QGXBDMJGAMFCBF-XYQQMQERSA-N (1S,2S,7S,10R,11S,15S)-5-hydroxy-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadecan-14-one Chemical compound C1C(O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC[C@H]21 QGXBDMJGAMFCBF-XYQQMQERSA-N 0.000 claims description 4
- RLAHWVDQYNDAGG-UHFFFAOYSA-N Orthoformic acid Chemical class OC(O)O RLAHWVDQYNDAGG-UHFFFAOYSA-N 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 4
- 150000002334 glycols Chemical class 0.000 claims description 4
- 230000001590 oxidative Effects 0.000 claims description 4
- 101700018994 ARYL Proteins 0.000 claims 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- 150000002148 esters Chemical class 0.000 description 18
- 239000000203 mixture Substances 0.000 description 14
- BDERNNFJNOPAEC-UHFFFAOYSA-N propanol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- WVDDGKGOMKODPV-UHFFFAOYSA-N benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 12
- LYCAIKOWRPUZTN-UHFFFAOYSA-N glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- -1 aryl alcohols Chemical class 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 8
- 230000000875 corresponding Effects 0.000 description 8
- 235000019441 ethanol Nutrition 0.000 description 8
- 229960003604 Testosterone Drugs 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 229960003473 androstanolone Drugs 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- GKGFTIKPKGWMOW-UHFFFAOYSA-N propane-1,1,1-triolate Chemical compound CCC([O-])([O-])[O-] GKGFTIKPKGWMOW-UHFFFAOYSA-N 0.000 description 6
- 235000019445 benzyl alcohol Nutrition 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- WGLPBDUCMAPZCE-UHFFFAOYSA-N trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 4
- QYIXCDOBOSTCEI-QCYZZNICSA-N (5α)-cholestan-3β-ol Chemical compound C([C@@H]1CC2)[C@@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@H](C)CCCC(C)C)[C@@]2(C)CC1 QYIXCDOBOSTCEI-QCYZZNICSA-N 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- DJTOLSNIKJIDFF-LOVVWNRFSA-N 5a-Androstan-3b-ol Chemical compound C([C@@H]1CC2)[C@@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CCC[C@@]2(C)CC1 DJTOLSNIKJIDFF-LOVVWNRFSA-N 0.000 description 2
- QZLYKIGBANMMBK-UGCZWRCOSA-N 5α-Androstane Chemical compound C([C@@H]1CC2)CCC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CCC[C@@]2(C)CC1 QZLYKIGBANMMBK-UGCZWRCOSA-N 0.000 description 2
- MWFMGBPGAXYFAR-UHFFFAOYSA-N Acetone cyanohydrin Chemical compound CC(C)(O)C#N MWFMGBPGAXYFAR-UHFFFAOYSA-N 0.000 description 2
- PSYPSFLCFZCTGH-LKCOYYOESA-N C(C)(=O)OC1[C@@H]2[C@](CC1)(C)CC[C@H]1[C@H]2CC[C@H]2CC(CC[C@]12C)=O Chemical compound C(C)(=O)OC1[C@@H]2[C@](CC1)(C)CC[C@H]1[C@H]2CC[C@H]2CC(CC[C@]12C)=O PSYPSFLCFZCTGH-LKCOYYOESA-N 0.000 description 2
- 241000862969 Stella Species 0.000 description 2
- 241000193803 Therea Species 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 150000001555 benzenes Chemical class 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 125000004432 carbon atoms Chemical group C* 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000005712 crystallization Effects 0.000 description 2
- IMROMDMJAWUWLK-UHFFFAOYSA-N ethenol Chemical compound OC=C IMROMDMJAWUWLK-UHFFFAOYSA-N 0.000 description 2
- 238000005755 formation reaction Methods 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L na2so4 Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 230000020477 pH reduction Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000001187 sodium carbonate Substances 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000001131 transforming Effects 0.000 description 2
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J75/00—Processes for the preparation of steroids in general
Definitions
- The'present invention relates to the manufacture of this'intermediate (III) and its further transformation into dihydrotestosterone (VI) or in its esters (VIII: Where R-CO:adicaloforganic acid according to a series .of reactions which are substantially analogous to those described in the above mentioned application.
- acetalysing agents may be also employed as for instance other esters of orthoformic acid, alcohols (e. g., benzyl alcohol), glycols (e. g., ethylene glycol) always in the'presence of catalysers of acid nature; intermediate products containing in position '3 the ketal groups corresponding to the acetalysing agents employed, are thus prepared:
- the cyanohydrin (II) (mixture of two l7-epimers: androstan-17-a-cyan-3fi-l7p-diol and androstan-17B-cyan- 3fl-17a-diol, M. P. dec. about 170 C.) is used in the crude state, simply well washed with petrol ether and dried in the vacuum.
- Th r action is carried out with the same pr eedut as in Example 1 using the same starting materials in the same quantities until the treatment with propyl alcohol and sodium of the 3-diethyl-ketal of androstandione-l7- monocyanohydrin (IV),
- the solution in propyl alcohol so obtained is diluted with water and allowed to crystallise.
- the separation of about 8 g. of crude 3- diethyl-ketal of androstan-l7fi-ol-3-one (V) M. P. 120-138 C. is obtained.
- the product is dissolved in 75 cc. of pyridine and acetylated'at room temperature by adding 35 cc. of acetic anhydride.
- a process for the preparation of 4-dihydrotestosterone which comprises oxidizing with chromic acid the cyanohydrin of androstan-3-ol-17-one to form androstana l7-cyan-l7-ol-3-one; treating this intermediate in the presence of an acid catalyst with an acetalysing agent, selected from the group consisting of QIlIh OfQllIliQ!
- a process as defined in claim 7wherin the acetalysing agent is ethyl orthoformate. 9.'A process asdefined iniclair'n 7 wherein the acetalysing agent is benzyl' alcohol; 10. A process as defined in claim 7 wherein the acetalysing agent is ethylene glycol.
Description
Mann,
United States Patent METIIOD FOR THE PREPARATION OF DIHYDRO- TESTOSTERONE AND ITS ESTERS Alberto .Ercoli' and Pietro de Ruggieri, Milan, Italy, assiguors to Francesco Vismara'Societa per Azioni, Como, Italy, a corporation of Italy, and Alberto Ercoli, Milan, Italy No Drawing. Application January 15, 1954,
. Serial No. 404,377
Claims. ((31. 260-5914 tained is then submitted to the combined-action of an aliphatic alcohol and an alkali metal, in order to obtain an enol ether or a ketal of testosterone from which finally the testosterone and its esters may be obtained. The applicants have now discovered that a process perfectly analogous is suitable also in the preparation of dihydrogenated (in position 4-5) testosterone, or androstanl7}8 -ol-3-one (VI), commonly known under the name of 4-dihydro-testosterone.
Inthis case the necessary intermediate is the androstan- The'present invention relates to the manufacture of this'intermediate (III) and its further transformation into dihydrotestosterone (VI) or in its esters (VIII: Where R-CO:adicaloforganic acid according to a series .of reactions which are substantially analogous to those described in the above mentioned application.
4 The process according to the invention may be illustrated by the scheme represented on the last page hereof In practicing containing the formulas from .I to VIII. our invention we proceed as follows:
- The cyanohydrin of androstan-Se-ol-l7-one or androstan-17-cyan-3B,l7-diol, mixture of two 17-epimers .(II)-'which may beeasily prepared from androstanproduct in its turnby treatment with sodium and propyl alcohol is transformed into a solution of S-diethyl-ketal of 4-dihydrotestosterone (V). The propyl alcohol solution containing the new intermediate, by acidification in ithe hot with dilute hydrochloric acid, yields directly the l 4-dihydrotestosterone (VI). also'be isolated by simple dilution of the propyl alcohol solution and the esters of the 4-dihydrotestosterone (VIII) may be obtained by acylation of the group OH in position 17, with intermediate formation of esters of 3- diethyl-ketal of .The intermediate V may the 4-dihydrotestosterone (VII): after-- to the solution.
2,734,066 Patented Feb. 7, 1955 hydrolysis the esters of 4-dihydrotestosterone (VIII) are obtained.
Instead of using the cyanohydrin of'androstan-BB-ol- -l7-one, the cyanohydrin of andro stan-3a-ol-l7-one may be also employed which, by chromic oxidation, yields the same intermediate III,
Instead of using ethyl orthoformate, other acetalysing agents may be also employed as for instance other esters of orthoformic acid, alcohols (e. g., benzyl alcohol), glycols (e. g., ethylene glycol) always in the'presence of catalysers of acid nature; intermediate products containing in position '3 the ketal groups corresponding to the acetalysing agents employed, are thus prepared:
and similar products) From androstan-3 8-ol-l7-one (I) as starting material or directly from the crude oxidation products of the dihydrocholesterol, the corresponding cyanohydrin (II) is prepared by action of acetone cyanohydrin (according to the French Patent No. 1,058,454 dated November 4,
The cyanohydrin (II) (mixture of two l7-epimers: androstan-17-a-cyan-3fi-l7p-diol and androstan-17B-cyan- 3fl-17a-diol, M. P. dec. about 170 C.) is used in the crude state, simply well washed with petrol ether and dried in the vacuum.
10 g. of this cyanohydrin are suspended in a mixture of cc. of ethylene chloride and 200 cc. of acetic acid. Then a solution of 3 g. of chromic anhydride in 60 cc. of acetic acid at is slowly added at the temperature of 15 C. during 15 minutes. The mixture is maintained in agitation. After 24 hours, ether and water are added The ethereal layer, which separates off, is repeatedly washed with water, dried over sodium sulfate and evaporated in the vacuum. A solid crystalline resi? due of about 8.85 g. is obtained which, recrystallised from ether, yields 8.35 g. of androstan-17-cyan-l7-ol-3- one (III) (mixture of two possible l7-epimers, M. P. 207 C. dec.). This intermediate will be called androstandione-17-monocyanohydrin hereinafter. I
8.35 g. of androstandione-l7-monocyanohydrin are suspended in cc. of benzene, then 55 cc. of benzene are distilled in order to eliminate moisture. The temperature is brought to 65 C. and, while maintaining it, 9.5 g. of ethyl orthoformate, 5 cc. of absolute ethyl alcohol and 0.43 cc. of a 7% hydrogen chloride solution in absolute ethyl alcohol (0.03 g. of HCl) are added. After 15 minutes all the original product goes into solution and a new crystallisation begins. After another 45 minutes at 65 'C., 0.075 cc. of pyridine are added and the solution is evaporated in the vacuum to dryness; a residue of 8.9 g. of crude 3-diethyl-ketal of androstandione-17- monocyanohydrin (IV) is obtained.
This residue is dissolved in 230 cc. of propyl alcohol and rea ed on t e boilin Wate at with 9 9i 594m?! in small pieces for about 30 minutes.
When the rea tio ashie etl he m xture hi h n cont in the ethYl-lteta o aadroetaaw l-- e (V), i aci ified o redo a th 2. N h teshl i q sidand diluted with boiling water. Most of the propyl alcohol i elim na ed by disti la ion at q lted @mswm nd en, by co lin an a lowi t9 re t er stella ie of 6.9 g f -di ydr es os emtie (VI) M- P- l l C. is obtained.
Example .2
Th r action is carried out with the same pr eedut as in Example 1 using the same starting materials in the same quantities until the treatment with propyl alcohol and sodium of the 3-diethyl-ketal of androstandione-l7- monocyanohydrin (IV), The solution in propyl alcohol so obtained is diluted with water and allowed to crystallise. The separation of about 8 g. of crude 3- diethyl-ketal of androstan-l7fi-ol-3-one (V) M. P. 120-138 C. is obtained. The product is dissolved in 75 cc. of pyridine and acetylated'at room temperature by adding 35 cc. of acetic anhydride. After a night the excess of acetic anhydride is decomposed by dilution with water and the acetyl derivative is extracted with ether. The ether, washed with dilute sodium carbonate nd w er, a t r s cc tion and vW pQ et O g es a residue of 3- diethyl-lcetal of 17fi acetoxy-androstan-3- one (VII where: R=CH3) in acrudestate. This product is dissolved in 35cc. of acetone and thesolution is heated with reflux for 10 minutes with addition of Q15 cc. of concentrated hydrochloric acid. The mixture is then diluted with water and allowed to cool: the product which separates off, after crystallisation-from petrol ether, yields about 7 go d yd ot t t i ne aestat 1 W1 R=CH3) M. P. 153156 C.
Similarly the other esters of dihydrotestosterone are prepared.
We claim:
1. A process for the preparation of 4-dihydrotestosterone which comprises oxidizing with chromic acid the cyanohydrin of androstan-3-ol-17-one to form androstana l7-cyan-l7-ol-3-one; treating this intermediate in the presence of an acid catalyst with an acetalysing agent, selected from the group consisting of QIlIh OfQllIliQ! acid esters, aryl alcohols and aliphatic glycols; therebyob taining as a sec ond interme'diate'a 3-ketal derivative of the androstan 17-cyan-17-ol-3-one;subjecting the second intermediate compound to the" concomitant aeti'onmft a boiling aliphatic alcohol of the series containing to carbon atoms and an alkali metal to eliminate the CN group in 17-position and to form in the alkaline alcoholic solution a 3-ketal derivative of 4-dihydrotestosterone, acidifying the said boiling alkaline alcoholic solution with a mineral acid and diluting the same with boiling water to obtain 4-dihydrotestosterone.
2. A process as defined inclaiml wherein the acetalysing agent isethyl iorthoforrnat'e." process as defined in'claim 1 wherein the acetalysiug agent is benzyl alcohol. 4."Aprloce:ss as defined-"in claim 1 wherein the acetalysing agent is ethylene glycol.
5. A process as defined 'incl'aim 1 wherein an acid of the group consisting of mineral and aromatic sulfonic acids is employed as catalyst in the" acetalysatior'i'jstep.
A process its definedin claim 1 wherein the acetalysation 'stepis carried but in presence 'ofa 'solv'ent 'of the series of benzene and its 'methyl'homologuels," and water formed inthe 'acetalys'ation is rem'mze'd b annua tion of the same solvent forming 'an azeotrop ic mixture therewith. I 6. A process as defined in claim 1 wherein the acetalysation step is carried out in presencecf'asolvent of cyanohydrin of androstan-3 ol 17-onejtdforni andrdstan- 17- cyan-17-ol 3-on'e; treating this intermediate'in the presence of an acid catalyst with anacetalysing agent selected from the group" consisting of orthofo'riiiicacid estersparyl alcohols and aliphatic glycols, ltlielebyobtaim ing as a second intermediate a 3-glycol ketal derivative" of 4- dihydrotestoisterone; diluting the said "alkaline alcoholic solution with water to precipitate and isolate"th 3-kelta'l derivative of 4-dihydrotestosterone'; acylating the" latter in the dried state at the OH group in 17-position with ai1 organic carboxylic acid anhydr'ide of the series of aliphatic acid anhydrides corresponding to the acids con- Itaining from 2 to 6 carbon 'atorns'Qinthe' presence of pyridine, to obtain a 17-acylesterof the 3-ketal derivative of 4-dihydrotestoster one; ,hy drolysin g the"3- ketal function of the latter by gentle boiling in""aceton'e ihithe presence of traces of mineral acid and water' to obtain the corresponding 4-dihydrotes tosterone-l7-acyl ester'l" 8. A process as defined in claim 7wherin the acetalysing agent is ethyl orthoformate. 9.'A process asdefined iniclair'n 7 wherein the acetalysing agent is benzyl' alcohol; 10. A process as defined in claim 7 wherein the acetalysing agent is ethylene glycol.
ReferencesVCited in the file of this patent UNITED STATES PATENTS Miescher .Oct. .28, .1941 Westphal Sept. 1,1942
FOREIGN PATENTS Switzerland Mar. .3, 1941
Claims (1)
1. A PROCESS FOR THE PREPARATION OF 4-DIHYDROTESTOSTERONE WHICH COMPRISES OXIDIZING WITH CHROMIC ACID THE CYANOHYDRIN OF ANDROSTAN-3-OL-17-ONE TO FORM ANDROSTAN17-CYAN-17-OL-3-ONE; TREATING THIS INTERMEDIATE IN THE PRESENCE OF AN ACID CATALYST WITH AN ACETALYSING AGENT, SELECTED FROM THE GROUP CONSISTING OF ORTHOFORMIC ACID ESTERS, ARYL ALCOHOLS AND ALIPHATIC GLYCOLS, THEREBY OBTAINING AS A SECOND INTERMEDIATE A 3-KETAL DERIVATIVE OF THE ANDROSTAN-17-CYAN-17-OL-3-ONE; SUBJECTING THE SECOND INTERMEDIATE COMPOUND TO THE CNCOMITANT ACTION OF A BOILING ALIPHATIC ALCOHOL OF THE SERIES CONTAINING 2 TO 5 CARBON ATOMS AND AN ALKALI METAL TO ELIMINATE THE CN GROUP IN 17-POSITION AND TO FORM IN THE ALKALINE ALCOHLIC SOLUTION A 3-KETAL DERIVATIVE OF 4-DIHYDROTESTOSTERONE, ACIDIFYING THE SAID BOILING ALKALINE ALCOHOLIC SOLUTION WITH A MINERAL ACID AND DILUTING THE SAME WITH BOILING WATER TO OBTAIN 4-DIHYDROTESTOSTERONE.
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US2734066A true US2734066A (en) | 1956-02-07 |
Family
ID=3443601
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US2734066D Expired - Lifetime US2734066A (en) | Method for the preparation of dfflydro- |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US2734066A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2853500A (en) * | 1956-08-13 | 1958-09-23 | Rubin Martin | Preparation of 1, 4-androstadien-3, 17 dione |
| US2940990A (en) * | 1956-05-22 | 1960-06-14 | Syntex Sa | 17-diacetals of estrone |
| US2940989A (en) * | 1955-06-01 | 1960-06-14 | Syntex S A Mexico City | 19-nor-17alpha ethinyl-androstan-17beta-ol-3-one |
| US3055921A (en) * | 1956-01-05 | 1962-09-25 | Sterling Drug Inc | 17-cyano-17-oxy-steroids and 17-aminomethyl-17-oxy-steroids |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB461335A (en) * | 1935-08-19 | 1937-02-15 | Chem Ind Basel | Manufacture of polynuclear cyclic oxyketones and esters thereof |
| CH212190A (en) * | 1935-11-23 | 1940-11-15 | Chem Ind Basel | Process for the preparation of a new oxyketone of the androstane series. |
| US2260328A (en) * | 1935-06-18 | 1941-10-28 | Ciba Pharm Prod Inc | Process for the manufacture of alpha-beta-unsaturated ketones of the cyclopentanopolyhydrophenanthrene series |
| US2294433A (en) * | 1937-10-05 | 1942-09-01 | Schering Corp | Hydroxy ketones of the cyclopentanopolyhydrophenanthrene series and method of producing the same |
| CH274087A (en) * | 1948-11-17 | 1951-03-15 | Ciba Geigy | Process for reducing a compound of the cyclopentanopolyhydrophenanthrene series. |
-
0
- US US2734066D patent/US2734066A/en not_active Expired - Lifetime
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2260328A (en) * | 1935-06-18 | 1941-10-28 | Ciba Pharm Prod Inc | Process for the manufacture of alpha-beta-unsaturated ketones of the cyclopentanopolyhydrophenanthrene series |
| GB461335A (en) * | 1935-08-19 | 1937-02-15 | Chem Ind Basel | Manufacture of polynuclear cyclic oxyketones and esters thereof |
| CH212190A (en) * | 1935-11-23 | 1940-11-15 | Chem Ind Basel | Process for the preparation of a new oxyketone of the androstane series. |
| US2294433A (en) * | 1937-10-05 | 1942-09-01 | Schering Corp | Hydroxy ketones of the cyclopentanopolyhydrophenanthrene series and method of producing the same |
| CH274087A (en) * | 1948-11-17 | 1951-03-15 | Ciba Geigy | Process for reducing a compound of the cyclopentanopolyhydrophenanthrene series. |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2940989A (en) * | 1955-06-01 | 1960-06-14 | Syntex S A Mexico City | 19-nor-17alpha ethinyl-androstan-17beta-ol-3-one |
| US3055921A (en) * | 1956-01-05 | 1962-09-25 | Sterling Drug Inc | 17-cyano-17-oxy-steroids and 17-aminomethyl-17-oxy-steroids |
| US2940990A (en) * | 1956-05-22 | 1960-06-14 | Syntex Sa | 17-diacetals of estrone |
| US2853500A (en) * | 1956-08-13 | 1958-09-23 | Rubin Martin | Preparation of 1, 4-androstadien-3, 17 dione |
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