2,409,293 Patented Oct. 15, 1946 UNITED STATES PATENT orrlcsd HORMONE INTERNIEDIATES AND PREP. ARATION 0F SAlVlE , ' Russell Earl Marker, MexicoCity, Mexico, assign or to Parke, Davis 8; Company, Detroit, Mich, a corporation of Michigan No Drawing. Original application June 30, 1941, Serial No. 400,559., Divided and this applica tion May 24, 1944, Serial No. 537,201 5 Claims. (C1, 260-—397.4) 2 other substance containing reactive hydrogen,’ for example, the combination of sodium metal and ethyl alcohol, leads to the formation of 9. 20(00 -hydroxypregnane compound whichmay be represented by the following partial formula, This invention relates to the preparation of certain hormone intermediates, and this applica tion is a division of my copending application, Serial No. 400,559, ?led June 30, 1941, now Patent No. 2,352,648, issued July 4, 1944. In my copending application, Serial No. 393, 667, ?led May 15, 1941, now Patent No. 2,352,852, issued July 4, 1944, it is shown that steroidal CH3 CH3 (11H . . . OHM) sapogenins can be converted into a new class of compounds which I designate as pseudo-sapogen ins including pseudo-sapogenin eXo-acylates. In my copending application, Serial No. 382, Where the term 20-(a) -hydroxy occurs in this 451, ?led March 8, 1941, now Patent No. 2,352,850, speci?cation, it will be understood that this term issued July 4, 1944, it is shown that diosgenin refers to one of the two epimers theoretically may be converted into pseudo-diosgenin diace 15 possible. See further R. E. Marker et al., J. Am. tate. Chem. Soc., 59, 2291 (1937). In the copending application of Marker, Crooks My invention may be illustrated by the follow & Wittle, Serial No. 393,666, ?led May 15, 1941, ing examples. now Patent No. 2,352,851, issued July 4, 1944, (a) Diosgenin is treated as set forth‘ more there is described the oxidation of pseudo-sapo 20 fully in my copending Patent No. 2,352,850 for genin exo-acylates to give a new class of esters six to ?fteen hours with acetic anhydride at designated 20-keto-16-(e-acyloxy-isocaprooxy) 200° 0., thereby forming pseudo-diosgenin di acetate. After crystallization from methanol, pregnane compounds represented by the partial formula the pseudo-diosgenin diacetate has a melting ' 25 point of 97-100" 0. CHa CH2 (b) Pseudo-diosgenin diacetate is oxidized with chromic anhydride in acetic acid at 28° 0., =0 as set forth more fully in the copending Patent No. 2,352,851. Thus there is obtained the corre 30 sponding 20 - keto - l6 - (6-acyloxy-isocaprooxy) - pregnane compound of melting point 85-86“ C. This compound is believed to have the structure, In my Patent No. 2,352,648, I have described and claimed a process comprising the reduction ll CHz-C-o by non-hydrolytic reagents of a 20-keto-16-(6 acyloxy-isocaprooxy)-pregnane compounds and subsequent treatment with a hydrolytic agent to obtain a 20(5), l?-dihydroxypregnane compound. According to the invention in this divisional application, instead of using non-hydrolytic re ducing agents, I employ reducing agents which also have a hydrolytic action thereby completely removing the group at C16. Thus, reduction of a 20-keto-16-(6-acyloxy isocaprooxy) -pregnane compound with the com and it may be designated as As-pregnenediol 45 3(5) ,16 - one - 20 3 - acetate-l6-(a-acetoxy) -iso caproate. , (c) To 2 g. of the product, melting point 85-86° 0., designated as A5-pregnenediol-3-(B) ,16-one 20 3-acetate-16-(6-acetoxy) -isocaproate, in 200 cc. of dry isopropyl alcohol is added 15 g. of so dium in small pieces. The mixture is re?uxed for about an hour or until all the sodium has been dis solved. Thereupon water is added and the mix ture extracted well with ether. vThe ethereal layer is washed with water and then the ether is bination of an alkali metal and. an alcohol or 55 2,409,293 3 removed on a steam bath. The residue is crystal consisting of hydroxyl and groups hydrolyzable lized from dilute acetone and from dilute meth to hydroxyl, to the action of an alkali metal in combination with an alcohol reactive with said anol and thus yields A5-pregnenedio1-3-(?) ,20 (a) of melting point 171-176“ C. alkali metal to form nascent hydrogen, thereby The structure of the above product is shown by 5 producing a steroid of the formula the fact that it may :be hydrogenated in the pres CH: ence of glacial acetic acid and a platinum oxide CH: OH: catalyst to yield allo-pregnanediol-B-(?),ZO-(u) of melting point 214-216? C. The above examples are intended to illustrate 10 but not to limit the scope of my invention. Other modes of employing my processapparent to those skilled in the art after this disclosure, are, in tended to fall within the scope of my invention and accordingly I wish to limit the scope of my invention only as indicated in the appended claims. What I claim as my invention is: 1. Process for preparing hydroxy-pregnane de rivatives which comprise subjecting a steroid hav ing in ring D the structure 20 _/ /\ “bx/l \) 'ILA 3. Process for preparing hydroxy-pregnane de rivatives which comprises subjecting a steroid of the formula CH3 CH3 CH3 I o C= CH3 H . . . OH(c<) CH: (I) \ ___/ OH: l- H:- O ~acy l 0 (JJ CH2- CH2- (EHO ——— D I 25 CH: YL/V to the action of an alkali metal in combination with an alcohol reactive with said alkali metal to hydroxyl and groups hydrolyzable to hydroxyl, form nascent hydrogen, thereby producing a ster oid having in ring D the structure to‘ the action of an alkali metal in combination with an alcohol reactive With said alkali metal where Y is a member of the class consisting of to form nascent hydrogen, thereby producing a steroid of the formula CH: cm. on . . . one!) 35 CH: Dl H . . . OHM) / \/ 2. Process for preparing hydroxy-pregnane de- 40 rlvatives which comprises subjecting a steroid of the formula CH3 CH: CH3 =0 .. / I (H) 4o CH1: ‘ 5 6 HA where 71A represents 11 carbon-to-carbon double bonds between C5 and C5, 11 having one of the values 0 and 1, and Y is a member of the class I /\ V How 4. Process for preparing A5-pregnenediol—3 (/3),20-(u) which comprises subjecting Ali-preg nenediol - 3-(5) ,16-one-20 3-acetate-16-(6-acet oxy)-isocaproate to the action of a alkali metal in combination with an alcohol reactive with said alkali metal to form nascent hydrogen. V-O-C-CHz-CHz-élH-CHz-O-ac? Y CHa OH: 50 5. Process for preparing A5-pregnenediol-3 (,B),20—(a) which comprises subjecting A5-preg nenediol - 3-(p),16-one-20 3-acetate-l6-(6-acet oxy) -isocaproate to the action of sodium and iso propyl alcohol. RUSSELL EARL MARKER.