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#Are useful as anti-inflammatory agents. In formula I, and throughout the specification, the symbols are as defined below:
#R.sub.1 can be hydrogen, hydroxy, halogen or acyloxy;
Detailed description2,017 words
#The following examples are specific embodiments of this invention.
#A solution of 5 g of 9-fluoro-11.beta.,21-dihydroxypregna-1,4,16-triene-3,20-dione, 21-acetate, 50 ml each of acetic anhydride and dichloromethane and 2.5 ml of boron trifluoride etherate is stirred at room temperature under nitrogen for 2.5 hours. Because the reaction is slow, another 1.5 ml of boron trifluoride etherate is added and the reaction is continued for another 1.5 hours. The resulting solution is diluted with 200 ml of dichloromethane, washed with a saturated sodium bicarbonate solution and water, dried over anhydrous sodium sulfate and evaporated in vacuo to give 5.2 g of a solid. This is chromatographed on a column of 100 g of silica gel. Elution with 1:4 hexane-chloroform gives 4.8 g of material. Crystallization from chloroform-hexane gives 4.2 g of the title compound, melting point 294-296.degree.C.
#A solution of 1.8 g of 11.beta.,21-bis(acetyloxy)-9-fluoropregna-1,4,16-triene-3,20-dione and 600 mg of anhydrous aluminum chloride in 35 ml of dichloromethane is stirred for 1 hour under nitrogen to afford a homogeneous solution. To this is added dropwise a solution of 2,3-dimethyl-1,3-butadiene (3.0 ml) in dry dichloromethane (5.0 ml). After 1 hour the mixture is diluted with dichloromethane (250 ml), washed with a 10% sodium bicarbonate solution and water, dried over anhydrous sodium sulfate, and evaporated in vacuo to give 6.3 g of an oil. This is dissolved in 1:3 hexane-chloroform and chromatographed on a column of silica gel (150 g). Elution with 3:2 hexane-chloroform and 1:1 hexane-chloroform gives 1.8 g of a homogeneous solid. This is dissolved in a mixture of tetrahydrofuran (50 ml) and methanol (40 ml), and a 10% potassium carbonate solution (0.95 ml) is added and stirred under nitrogen at 0.degree.C for 2.0 hours and at room temperature for 4.5 hours. The resulting solution is neutralized with 5% acetic acid. The solvent is then partially removed in vacuo and the slurry is extracted with chloroform. The chloroform solution is washed with water, dried over anhydrous sodium sulfate and evaporated in vacuo to give 1.5 g of a foam. This is dissolved in chloroform and chromatographed on a column of silica gel (60 g). Elution with 1:3 hexane-chloroform and chloroform gives 1.2 g of material. Crystallization from chloroform-hexane gives 760 mg of the title compound, melting point 256.degree.-258.degree.C.