PROCESS FOR THE PREPARATION OF DEBROMINATED ANALOGUES OF BROMO-STEROIDS OF THE PREGNANE,ANDROSTANE AND CHOLESTANE SERIES

摘要

The invention comprises (i) a process for dechlorinating, debrominating or deiodinating organic compounds by reaction in the presence of a transfer donor of free hydrogen atoms with (a) a reducing agent or system supplying metal ions in a lower valency state capable of ready oxidation to a higher valency state or (b) a reducing system comprising a metal and a liquid which dissolves the metal so as to increase its valency and so reduce other substances present, and (ii) 11b -fluoro-D 4-9a -pregnene-17a ,21-diol-3,20-diones and their 21-esters, 11b -fluoro-D 1,4-9a - pregnadiene - 17a ,21 - diol - 3,20 - dione- 21 - acetate and 11b - fluoro - 16a - methyl - D 1,4 - 9a - pregnadiene - 17a ,21 - diol - 3,20-dione 21-ethyl carbonate, and their preparation by 9a -dehalogenation. 9a -Bromo-prednisolone acetate is prepared by heating prednisolone acetate with methanesulphonyl chloride, pyridine and dimethylformamide, followed by sodium bicarbonate solution, to give D 1,4,9(11)-pregnatriene-17a ,21-diol -3,20-dione-21-acetate, followed by treatment with perchloric acid and N-bromoacetamide. 9a - Bromo - pregna - 1,4 - dien - 11b - ol - 3,20-dione is prepared by treatment of the corresponding 1,4,9(11)-triene with perchloric acid and N-bromo-acetamide. 9a - Bromo - 11b - fluoro - 16a - methyl - pregna-1,4 -diene-17a ,21-diol-3,20-dione-21-ethyl carbonate is prepared by treatment of the corresponding 1,4,9(11)-triene with anhydrous hydrogen fluoride and N-bromo-acetamide. 11b -Hydroxy-5,9-cyclo-pregnane-3,20-dione is obtained as a by-product from the reductive debromination of 9a -bromo-11b -hydroxy-progesterone. Chromous acetate is obtained by reduction of chromic chloride hexahydrate with amalgamated zinc dust to give a solution of chromous chloride, and adding this to a sodium acetate solution.