1-溴-6-氯己烷

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: First 30 ml of a solution that consists of 41 ml of 1-bromo-6-chlorohexane in 270 ml of THF is added to a suspension of 6.8 g of magnesium chips in 100 ml of THF. After the reaction starts, the remaining solution is added in drops in such a way that the internal temperature does not exceed 35° C. In a second flask, 48.1 g of lithium bromide is added to a suspension of 26.4 g of copper(I) iodide in 120 ml of THF at 0° C., whereby the internal temperature climbs to 40° C. Without cooling, 46.4 ml of 1,3-dimethyl-3,4,5,6-tetrahydro-(1H)-pyrimidin-2-one is now added and stirred for 30 minutes at 40° C. A clear solution is obtained, which is added in drops to the Grignard solution that is cooled to -40° C. Then, it is stirred for 30 more minutes at -30° C. and mixed drop by drop at -50° C. with a solution of 23.5 g of 11β-fluoro-estra-4,6-diene-3,17-dione in 230 ml of THF, 24.6 ml of 1,3-dimethyl-3,4,5,6-tetrahydro-(1H)-pyrimidin-2-one and 55 ml of trimethyl-chlorosilane in such a way that the internal temperature does not exceed -40° C. It is stirred for 1 hour cold, then 32 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 1.51 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, 25.2 g of 7α-(6-chlorohexyl)-11β-fluoro-estr-4-ene-3,17-dione is obtained. the remaining solution is added in drops in such a way that the internal temperature does not exceed 35° C climbs to 40° C Without cooling A clear solution is obtained which is added in drops to the Grignard solution that is cooled to -40° C Then, it is stirred for 30 more minutes at -30° C. does not exceed -40° C It is stirred for 1 hour cold the cooling bath is removed stirred for 1 more hour at room temperature the reaction mixture is added to 1.51 of water diluted with the same amount of ethyl acetate the precipitate is separated on Celite the aqueous phase is extracted 3 times with ethyl acetate washed with sodium bicarbonate and common salt solution dried on magnesium sulfate concentrated by evaporation in a vacuum After the crude product is chromatographed on silica gel with a hexane-ethyl acetate gradient

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: This example illustrates a synthesis of 1-(16,17-Oxidoheptadecyl)-3,7-dimethylxanthine (inventive compound no. 3516). To a suspension of magnesium (3.10 g, 129 mmol) and a crystal of iodine in THF (10 mL) was added 10-undecenyl bromide (6.00 g, 25.8 mmol, available from MTM) in THF (20 mL) over 40 minutes and the reaction stirred for a further 30 minutes after the addition was complete. The solution was added via a canula over 50 minutes to a suspension of copper iodide (0.50 g, 2.58 mmol) and 1-bromo-6-chloro hexane (6.00 mL, 40.0 mmol) in THF (20 mL) and stirred at 25° C. for 16 hours. Sulfuric acid (1.0M, 50 mL) was added, extracted with diethyl ether (2×60 mL) and the organic solvent dried using magnesium sulfate and the solvent subsequently evaporated. The residue was distilled at 0.75 mmHg to yield 1.78 g (25% yield, b.p. 130°-135° C.) 16-heptadecenyl chloride as a colourless liquid. after the addition stirred at 25° C. for 16 hours extracted with diethyl ether (2×60 mL) the organic solvent dried the solvent subsequently evaporated The residue was distilled at 0.75 mmHg

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir: