GB452238A — Process for purifying progesterone preparations

USPTO Abstract

The hydroxylated impurities are removed from crude progesterone preparations by treatment of the preparations with an acylating agent followed by separation of the portion which has entered into reaction from the non-esterified portion which contains the progesterone. Suitable acylating agents which yield sparingly soluble esters with the oxyketones are benzoyl, nitrobenzoyl, dinitrobenzoyl, and phenylbenzoyl chlorides, phenylisocyanate, diphenylisocyanate, and phosgene. It is preferred, however, to use agents which in addition to the acylating group, contain a salt forming group or a group which can be transformed into a salt forming group such as phthalic and maleic acid anhydrides, oxybenzoic acid chlorides, chlorosulphonic acid, phosphorus oxychloride and alkyl-meta-phosphates. In examples: (1) a crude progesterone crystallisate is reacted with phthalic anhydride in an atmosphere of nitrogen, the aqueous solution extracted with ether, and the ether extract washed with hydrochloric acid and water. Evaporation of the ether and recrystallization of the product yields progesterone in two polymorphous forms. The hydroxylated compounds may also if desired be extracted from the aqueous solution; (2) a crude progesterone crystallisate is reacted with 2 : 4-dinitrobenzoyl chloride in quinoline solution, the product mixed with water, extracted with ether, and worked up to yield the two polymorphous forms as in example 1; (3) a progesterone crystallisate is reacted with phthalic anhydride in pyridine, and worked up as in example 1.