Iodine → 7alpha-(5-Chloropentyl)-11beta-fluor-estr-4-ene-3,17-dione

Participants

Reaction Conditions

Reaction Steps

First 20% of a solution of 39 ml of 1-bromo-5-chloropentane in 300 ml of THF is added under nitrogen to a suspension of 7.2 g of magnesium chips in 100 ml of THF. After the reaction has started, which can be achieved by adding iodine and dibromomethane, the residual solution is added in drops in such a way that the internal temperature does not exceed 35° C. In a second flask, 51.2 g of lithium bromide is added to a suspension of 28.1 g of copper(I) iodide in 130 ml of THF at 0° C., whereby the internal temperature climbs to 40° C. Without cooling, 49.4 ml of 1,3-dimethyl-3,4,5,6-tetrahydro-(1H)-pyrimidin-2-one is now added and stirred for 15 minutes at 40° C. A clear solution is obtained, which was added in drops to the Grignard solution that is cooled to −50° C. Then, it is stirred for 15 more minutes at −30° C. and mixed at −70° C. drop by drop with a solution of 25 g of 11β-fluor-estra-4,6-diene-3,17-dione in 260 ml of THF, 26 ml of 1,3-dimethyl-3,4,5,6-tetrahydro-(1H)-pyrimidin-2-one and 59 ml of trimethylchlorosilane in such a way that the internal temperature does not exceed −65° C. It is stirred for 30 minutes under cold conditions, then 34.7 ml of glacial acetic acid is added in drops, the cooling bath is removed and stirred for 1 more hour at room temperature. For working-up, the reaction mixture is added to 1.5 l of water, diluted with the same amount of ethyl acetate, the precipitate is separated on Celite, rewashed with ethyl acetate, the aqueous phase is extracted 3 times with ethyl acetate, washed with sodium bicarbonate and common salt solution, dried on magnesium sulfate and concentrated by evaporation in a vacuum. After the crude product is chromatographed on silica gel with a hexane-ethyl acetate gradient, 22.1 g of 7α-(5-chloropentyl)-11β-fluor-estr-4-ene-3,17-dione is obtained.

Provenance & Evidence