Patent GB-674300-A (GB)
Title: Manufacture of pregnanes
IPC: F25J1/00
Filed: 1950-07-14
Abstract: Compounds of the pregnane series are manufactured by oxidizing a pregnane-(20) alkyl ketone by means of a per-acid (with or without the addition of an acid catalyst, e.g. sulphuric, perchloric or p-toluenesulphonic acid) to form a 20-acyloxypregnane compound, and, if desired, hydrolysing and further oxidizing this (e.g. by means of choromium trioxide, permanganates, or metal alcoholates or phenolates together with ketones) to a 20-ketopregnane.  The starting materials may contain nuclear double bonds (e.g. in the 5 : 6- or 11 : 12-position), these preferably being temporarily protected (e.g. by addition of halogen or hydrogen halide, which is subsequently split off again).  Nuclear substituents may also be present, e.g. an 11-keto group, or (especially in one or more of the 3-, 7-, 11- and 12-positions) a free or substituted (e.g. acylated) hydroxy group, which may be converted to a keto group by oxidation, or hydrolysis and oxidation, after the oxidation with the per-acid, either simulataneously with the corresponding p  further treatment of the 20-substistituents or as a separate operation.  When the oxidation with a per-acid is effected in the absence of an acid catalyst, oxidation of a free 3-hydroxy group occurs at this stage.  In examples: (1) D 5-3b -acetoxypregnenyl-(20) methyl ketone is brominated in carbon tetrachloride, oxidized with perbenzoic acid in chloroform and acetic acid in the presence of sulphuric acid, and debrominated with zinc dust and glacial acetic acid, yielding D 5-pregnene-3b  : 20a -diol diacetate; by hydrolysing this with aqueous methanolic potassium carbonate, or by oxidizing D 5-3b -hydroxypregnenyl-(20) methyl ketone with monoperphthalic acid in the presence of p-toluenesulphonic acid (with protection of the double bond with bromine), there is obtained the corresponding 20-monoacetate, which is oxidized with cyclohexanone and aluminium isopropylate in toluene to D 5-3-ketopregnene-20a -ol acetate; (2) the diacetate from (1) is refluxed with methanolic caustic potash to form the corresponding diol, which is oxidized with cyclohexanone and aluminium isopropylate in toluene; the product is chromatographed to separate progesterone and D 4-3-ketoprenene-20-ol, and the latter (which is also obtained by boiling the final product of (1) with methanolic caustic potash) is oxidized to progesterone by means of chromic acid in acetic acid and carbon tetrachloride; (3) the starting materials in (1) are replaced by the corresponding isopregneyl compounds, and the product is boiled with methanolic caustic potash to give D 5-3-ketopregnene-20b -ol, also obtained by boiling the 20-monoacetate or diacetate of D 5-pregnene-3b -20b -diol with methanolic caustic potash and oxidizing the resulting diol with cyclohexanone and aluminium isopropylate; (4) the D 5-pregnene-3b -20b -diol from (3) is brominated in carbon tetrachloride and acetic acid, oxidized with chromic acid, and debrominated with zinc and glacial acetic acid, yielding, after chromatography, progesterone, which is also produced by similarly oxidizing D 4-3-ketopregnene-20b -ol (but without protection of the double bond).