Verfahren zur Herstellung neuer Derivate von gestagenen Hormonen

The invention comprises steroids of the general formula wherein R represents hydrogen or a halogen of a free or a carboxylic esterified hydroxy group, R1 represents an aliphatic, cycloaliphatic or arylaliphatic hydrocarbon group containing from 4 to 7 carbon atoms, X represents hydrogen, fluorine or chlorine or the methyl group, Y is hydrogen or the methyl group, and Z represents hydrogen or the methyl or a free or a carboxylic esterified hydroxy group with the limitation that X, Y and Z do not all represent hydrogen except when R represents a halogen, but when one of these symbols is other than hydrogen the other two symbols represent hydrogen, and the preparation thereof by reacting a corresponding D 4-3-keto-steroid with an alcohol of the formula R1OH wherein R1 has the above significance, in the presence of an acid catalyst and a lower alkyl orthoformate in solution in an organic solvent. A preferred method of preparation comprises reacting the D 4-3-keto-steroid with a lower alkyl orthoformate in the presence of an acid catalyst and then reacting the lower alkyl enol ether of the D 4-3-keto-steroid with the alcohol R1OH. Pharmaceutical compositions having a progestational effect comprise one or more steroids of the above general formula and a non-toxic liquid or solid pharmaceutical carrier. Preferred carriers are oils such as olive, sesame, linseed, wheat germ, sunflower seed, egg yolk or pine oil. 6b -Chloro(and fluoro)-progesterone are prepared by treating progesterone ethyl enol ether with N-chlorosuccinimide and glacial acetic acid and with perchloryl fluoride respectively. 2a -Methyl-17a -acetoxy-progesterone is prepared by treating 17a -hydroxy-pregnenolone with ethyl glycol in the presence of p-toluenesulphonic acid, treating the resulting 20-ethylene ketal of 17a -hydroxy-pregnenolone with cyclohexanone and aluminium isopropylate, treating the resulting 20-ethylene ketal of progesterone with sodium hydride and diethyl oxalate to form the sodium salt of the 20-ethylene ketal of 2-ethoxyoxalyl-progesterone, reacting this compound with monopotassium phosphate, then with methyl iodide and finally with sodium methylate to form 2a -methyl-17a -hydroxy-progesterone, and acetylating this compound. 16a -Acetoxy - 17a - hydroxy - progesterone is prepared by treating pregna-4,16-dien-3,20-dione with osmium tetroxide or potassium permanganate, and acetylating the resulting 16a ,17a -dihydroxy-progesterone. 16a -Methyl-progesterone