DE1593385B - Process for the preparation of 18-oxo compounds of the 5alpha- or 5beta-D-homoandrostane series or of 3-methoxy-20-oxo-19-nor-1,3,5 (10) -pregnatriene-18al-20-ethylene ketal. Eliminated from: 1260466 - Google Patents

Description

For example, for 20 ml of a 0.172 m lithium aluminum hydride

DW / S-acetoxy-n-oxo-D-homo-Sa-androstane-IS-al solution in tetrahydrofuran was a tetrahydrofuran

17-äthvlen-ketaI furan solution of 138.5 mg of the nitrate within

65 added for 30 minutes with ice cooling and stirring

A solution of 160 mg of dl-SjS-acetoxy-H-oxo-D- and then for 3 hours at room temperature

homo-5a-androstane-18-nitrile-ethylene ketal, which reacted with stirring. The reaction

by ketalization of the 17-ketone with ethylene glycol mixture was cooled and this 10 ml of water

added, then refluxed for 8 minutes for the purpose of hydrolyzing the imino compound heated. After concentrating to J4 volume under reduced pressure, the reaction mixture became with Acetic acid neutralized and extracted three times with chloroform. The chloroform solution was made with water washed, dehydrated, distilled to drive off the solvent, after which 142.4 mg are obtained as a residue became. This was made with 1.5 ml of acetic anhydride and 2.5 ml of pyridine at room temperature acetylated overnight. A crude product was obtained from the above reaction mixture after the usual treatment; 160 mg of the same were added to 8 g Chromatographed clay (Woelm III, neutral). From the fraction of petroleum ether-benzene (9: 1 to_2: l) were after recrystallization with acetone-ether

50.3 mg of the crystalline aldehyde, dl-3 /? - acetoxy-17-oxo-D-homo-Sa-androstane-18-al-17-ethylene ketal obtained with F = 170 to 179 ° C. Further recrystallization of the mother liquor gave more

20.4 mg. The combined crystals, that is 70.7 mg, showed no decrease after mixing with a sample obtained in Example 1 above.

Example3

3-methoxy-18-imino-19-norpregna-1,3,5 (10) -triene-20-

on-ethylene ketal and

3-methoxy-20-oxo-19-norpregna-1,3,5 (10) -triene-18-al-20-ethylene ketal

To a solution of 286 mg of S-norpregna-1,3,5 (10) -triene-18-nitrile-20-ethylene ketal in 15 ml of tetrahydrofuran was a solution of 290 mg of lithium aluminum hydride in 55 ml of tetrahydrofuran dropped in at room temperature with stirring. The reaction temperature gradually rose by mild heating; then the mixture was refluxed for 4 hours. After adding 2 ml of a solution of potassium sodium tartrate and one ml of a solution of tartaric acid with ice-cooling the upper organic layer was decanted and the lower water layer three times with chloroform extracted. The combined organic layers were washed with water, dried, and after Distilling off the solvent gave 297.6 mg of an oily substance which recrystallizes from acetone-ether would. The crystals of 3-methoxy-18-imino-19-norpregna-1,3,5 (10) -trien-20-one ethyl ketal obtained in this way had an F = 147 to 151 ° C.

CHCl ₃
Max

1633 (NH) Cm- ¹

Analysis: Calculated for C ₂₃ H ₃₁ O ₃ N (369.49):

C, 74.76 H, 8.46
Found: C, 75.12 H, 8.39

282 mg of the crystals obtained above were dissolved in 27 ml of methanol and 3 ml of 2N sodium hydroxide and refluxed for 10 minutes in a nitrogen atmosphere. After removing the solvent water was added to the mixture by distillation and then extracted three times with chloroform. The extracts were combined and washed with water, dried and distilled to remove the solvent, leaving 281 mg of an oily substance lag behind. This product was chromatographed on 15 g of clay (Woelm neutral) and from the Eluate from petroleum ether-benzene (1: 1) - benzene 135.4 mg 3-methoxy-20-oxo-19-norpregna-1,3,5 (10) -triene-18-al-20-ethylene ketal receive; after recrystallization from acetone-ether, an F = 157 to 162 ° C was found.

IR: γ ^CHCl 3 1712 (CHO) cm " ¹

^r max ^v '

Analysis: calculated TUrC ₂₃ H ₃₀ O ₄ (370.47):

C, 74.56 H, 8.16
found: C, 74.56 H, 8.04

The subsequent eluates with the aid of solvents such as benzene-benzene-chloroform (4: 1) gave 27.7 mg of the 18-imino compound, which was identical to the sample obtained above.

Claims (1)

Patent claim: ^erha I ^th ™ ^urde> "\ Λ ^ml tetrahydrofuran ^r was added dropwise with stirring and external cooling in process for the preparation of 18-Oxoverbin- a tetrahydrofuran solution of lithium Aluminidungen of 5a or 5 / SD-homo-androstane umdiäthoxyhydrid , obtained from 15.5 ml of 0.312 m-Li or from 3-methoxy-20-oxo-19-nor-l, 3.5 (10) -preg- 5 thium-aluminum hydride solution in tetrahydrofuran sodium-18-al- 20-ethylene ketal ₅ and 350 ml of ethyl acetate, within 5 minutes indicates that a corresponding one is added. The mixture was 5a- or 5 / SD-homoandrostane-18-nitrile or at the same temperature and then 3 , Stirred for 5 hours at 3-methoxy-20-oxo-19-nor-l, 3,5 (10) -pregnatriene- room temperature and cooled; the mixture of 18-nitrile-20-ethylene ketal in an organic solution was then added to 4 ml of 0.886 M sodium potassium tarsing agent with an alkali metal aluminum hydrate solution and 0.36 ml of 0.5 M tartaric acid solution hindrid or its alkoxy derivative reduced and the too and extracted three times with chloroform. The retained 18-imino compound in extracts known per se were washed with water, hydrolyzed under alkaline conditions, dried and distilled under reduced pressure, in each case further in the molecule, after which 214 mg of the residue were obtained, temporarily borrowed carbonyl groups be protected by this corresponds to a mixture of the iminomethyl ketal formation. . compound and a small amount of aldehyde and the starting compound, as indicated by the IR loading mood was established; so the ab- Process for the production of 18-oxo compounds 20 sorption bands at 3508 and 3458 of the OH group, the 5a or 5 /? - D-homoandrostane series or from at 3258 and 1635 the - CH-NH group, the band 3-methoxy-20-oxo-19-nor-l, 3,5 (10) -pregnatrien-18-al- at 2218 of the CN group and 2700 and 1716 cm- ^{1 of} the 20-ethylene ketal. CHO group. The present invention relates to a process The residue was dissolved in 9 ml of methanol, and drive to the production of 18-oxo compounds of 25 after adding 1 ml of 2N sodium hydroxide 5a- or 5/3-D-homoandrostane series or from 3-Me- the solution was for 5 minutes under Rückthoxy-20-oxo-19-nor-1,3,5 (10) -pregnatrien-18-al-20 -flow treated. Ethylene ketal after neutralization with acetic acid. the reaction mixture is extracted three times with These compounds are important intermediates - chloroform. The combined extracts were with fertilize for the synthesis of steroids. '30 water washed, dried, the solvent The process according to the invention is thereby distilled off under reduced pressure, and the back indicates that one was a corresponding 5a or was with 3 ml of acetic anhydride and 5 ml 5/3-D-homoandrostane-18-nitrile or 3-methoxy-20- anhydrous pyridine at room temperature oxo-19-nor-l, 3,5 (10) -pregnatrien-18-nitril-20-ethylene- night acetylated. 224 mg of the crude product were ketal obtained in an organic solvent with a 35 after an ordinary treatment and on Alkali metal aluminum hydride or its alkoxyderi alumina (known under the trade name Woelm vat reduced and the 18-imino compound obtained in III, neutral) chromatographed. From the group of In a manner known per se under alkaline conditions, petroleum ether-benzene (4: 1 to 7: 3) were obtained 34.8 mg hydrolyzed, with others in the molecule dl-3 /? - acetoxy-17-oxo-r> -homo-5a-androstane-18-alb found Carbonyl groups temporarily through 40 17-ethylene ketal, which after recrystallization Ketal formation are protected. Acetone-Ether a product with F 172 to 169 ° C (below The Reduktipn is revealed in a common orga- smoke development), Niche solvents such as tetrahydrofuran or _N · 1 Ether, carried out. The choice of this solvent IR: « " al ²⁷⁴² ( ^CHO )> ²⁶⁸ ° ( ^CHO ) depends on the substrate, the reducing agent and the er 45 1726 f CH COO · CHO ") 1708 CCHO ^ awaited product As a reducing agent, _{m2 (Äth} ^ _lenke ' _{tal) j 12} 47, ₁₀₂₂ Lithium-Aluminum-hydnd, Natnum-Aluminum-ny- / qj ^ · COO) cm " ¹ drid, or lithium-aluminum-alkoxyhydride use ³ be det. The reduction usually works when analyzed: calculated for: C ₂₄ H ₃₆ O ₅ (404.53) Room temperature ahead of you, but in some cases 5 ° C, 71.25 H, 8.91 with respect to the inactivity of the cyano group is found: C, 71.00 H, 8.92
a higher temperature is used. The hydrolysis The second fraction from petroleum ether-benzene (3: 2 to binding using common methods such as 3: 7) yielded 62 mg of the starting material, which Alkali treatment and alumina chromatography, 55 carried out after recrystallization from acetone-ether an F = 230. Possibly showed up to 237 ° C in the starting material,
existing carbonyl groups become intermediates protected by ketal formation. Example 2 The following examples illustrate the er dW / S-acetoxy-n-oxo-D-homo-Sa-androstan-IS-al-n- inventive method. 60 ^ ethylene ketal