METHOD OF SYNTHESIS OF 17β-HYDROXY-11β-[4-(DIMETHYLAMINO)- -PHENYL]-17α-(PROP-1-INYL)-ESTRA-4,9-DIENE-ONE Russian patent published in 2001 - IPC

FIELD: organic chemistry, steroids, chemical technology. SUBSTANCE: invention relates to improvement of method of synthesis of 17β-hydroxy-11β-[4-(dimethylamino)phenyl] -17α-(prop-1-inyl)-estra-4,9-diene-3-one of the formula (I): 17β. Method is carried out by interaction of steroid derivative with 4-dimethylaminophenyl- -magnesium bromide in the presence of catalyst in medium of tetrahydrofuran followed by isolation of steroid arylketal using ammonium chloride saturated solution, dehydration and hydrolysis in the presence of acid agent in medium of solvent at the room temperature followed by isolation of the end product. Oxidation of steroid derivative of the general formula (III): 11β where a) R is H; b) R is tert.-Bu-17α is carried out with complex hydrogen peroxide/hexafluoroacetone in organic solvent in the presence of chiral interphase catalyst N-benzyl- quinium bromide in the mole ratio 1:2:(0.03-0.10), respectively, in the presence of pyridine. After separation of organic layer the compound of the formula (IV): is isolated with yields 91-96.5% depending on R where R has the above indicated values and 5, - and 5, Me₂Si-containing isomers in the ratio (7.5-14.2): 1, respectively, depending on R, and this compound is subjected for interaction with 4-dimethylaminophenyl-magnesium bromide synthesized by reaction of 4-dimethylaminophenyl bromide with pyrophore form of magnesium in the mole ratio 1:1.9, respectively, in the presence of copper chloride at 0-5 C. After separation of organic layer steroid arylketal of the general formula (II): where R has the above indicated values is isolated. Compound II purified by crystallization is subjected for dehydration with 25% solution of sulfuric acid in acetone in the mole ratio 1: 1.67: 8, respectively, followed by isolation of the end product by treatment of reaction solution with the base aqueous solution and filtration of precipitated end product. The yield of (I) is 73.6% as measured for compound (III). EFFECT: improved method of synthesis, increased yield. 3 cl, 1 dwg, 10 ex