GB838654A - Steroids and the production thereof - Google Patents

Abstract

Cortisone, hydrocortisone, D 1-cortisone and D 1-hydrocortisone are recovered from a binary solvent system comprising water and a watermiscible organic solvent having greater volatility than water and containing dissolved watersoluble non-volatile salts in a process which comprises evaporating solvent from said system at a pH not greater than 7.0 until the residual solvent system is approximately saturated with respect to said steroid alcohol under the conditions of evaporation, but if necessary adding water during evaporation to prevent excessive supersaturation, thus to produce a first residual system, cooling said first residual system to a crystallization temperature below 20 DEG C., maintaining said crystallization temperature until substantial crystallization of said steroid alcohol takes place in the system, evaporating the resultant mixture, containing crystals of said steroid alcohol to remove a substantial quantity of solvent under conditions of temperature and pressure so as to retain undissolved a substantial portion of steroid alcohol crystals and produce a second residual system to separate further crystals of steroid alcohol, the amount of water in the solvent system being such that sufficient is present at said final crystallization to retain in solution said non-volatile salts and to afford a fluid slurry of steroid alcohol crystals, and recovering said crystals from said fluid slurry. The binary solvent system may be prepared by adding to the corresponding steroid 21-ester dissolved in a lower alkanol, an aqueous solution of an alkali metal bicarbonate in excess of the theoretical required for saponification, permitting hydrolysis to the free steroid alcohol to proceed to substantial completion, acidifying the solution to a pH not greater than 7.0 by means of an acid, thereby producing an aqueous lower alkanol solution containing the free steroid alcohol and dissolved non-volatile salts and concentrating the acidified solution at a temperature within the range of 20 DEG to 45 DEG C. until the concentration of free steroid alcohol is approximately but not substantially greater than saturation. As starting esters there may be employed the 21-acetates of cortisone, D 1-cortisone, hydrocortisone and D 1-hydrocortisone. Specification 772,106 is referred to.