Process for the su00ecntese of D (17 244 ) - 13 - ethyl - 17 - hydroxy 18,19 - dinorpregn - 4 - and - 2 0 - ino - 3-one oxime of high purity.The invention relates to a process for the synthesis of D - (17 244 ) - 13 - ethyl - 17 - hydroxy - 1819 - dinorpregn - 4 - and - 20 - ino - 3ona - the maximum of high purity (hereinafter norelgestromin) through acetylation of D - norgestrel in position 17.Oximau00e7u00e3o oxo group in position 3 of the 17 - acetoxy derivative obtained and, finally, hidrolisau00e7u00e3o acetoxy group at position 17 of the derivative of 3 oxime obtained.The process according to the invention is as follows: the source material, D - (17 244 ) - 17 - hydroxy - 13 - ethyl - 1819 - dinorpregn - 4 - and - 20 - ino - 3-one (D - norgestrel) - purity of 93 - 94% - is acetylated with acetic anhydride in acetic acid, in the presence of zinc chloride and hydrogen chloride.Or perchloric acid 70% in an atmosphere of inert gas, and after the completion of the reaction, the excess acetic anhydride and byproduct of enol acetate are decomposed with aqueous hydrochloric acid.Then, the D - (17 244 ) - 17 - acetoxy - 13 - ethyl 18,19 - dinorpregn - 4 - and - 20 - ino - 3 - one is isolated from the reaction mixture by adding cold water, the product precipitate is filtered, washed with water, dried.Dissolved in dichloromethane or acetone and clarified with silica gel or aluminum oxide and charcoal.After the filtration of the resulting solution is clarified concentrated and the residue is recrystallised, D - (17 244 ) - 17 - acetoxy - 13 - ethyl - 1819 - dinorpregn - 4 - and - 20 - ino - 3-one obtained is interacted with hydroxyaluminium acetate or with hydroxyaluminium chloride in the presence of sodium acetate.Acetic acid in nitrogen atmosphere under vigorous stirring for about 1 hour after completion of the reaction, water is added, the product precipitate is filtered, washed with water.Dried and recrystallised, D - (17 244 ) - 17 - acetoxy - 13 - ethyl - 1819 - dinorpregn - 4 - and - 20 - ino - 3-one oxime obtained is hydrolyzed with an equivalent amount of alkali metal hydroxide to a solution of alcanol of C ~ 1 ~ C ~ 4 ~.In the nitrogen atmosphere between a temperature of approximately 5 - 38 198 C, under vigorous stirring.After completion of the reaction, the mixture is diluted with water and the pH of the resulting suspension is adjusted to 7.5 to 9 with acetic acid, the product precipitate is filtered, washed with water.Dry and the raw product is dissolved in ethanol, clarified with charcoal and after filtration of the clarified water is added to the solution obtained, the D - (17 244 ) - 17 - acetoxy - 13 - ethyl - 1819 - dinorpregn - 4 - and - 20 - ino - 3-one oxime precipitated in high purity is filtered, washed with water, and data cases recristalizada from ethanol.
展开▼
