Pyridine → 1alpha,3beta,25-tris[(tetrahydro-2H-pyran-2-yl)oxy]-cholest-5-en-23-yne

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Reaction Steps

In a 1.5 l 4-neck flask equipped with stirrer, 100 ml dropping funnel with pressure equalizer, 30-cm Dimroth condenser, thermometer and argon-supply, a solution of 16.85 g (0.1 mol) of 3-methyl-3[(tetrahydro-2H-pyran-2-yl)oxy]-but-1-yne (prepared from 3-hydroxy-3-methylbut-1-yne and 3,4-dihydro-2H-pyran) in 300 ml of dioxane with constant stirring and under argon for 30 min. at 9°, was added drop by drop 50 ml (approximately 0.1 ml) of approximately 2 M n-butyl lithium in hexane. The solution was stirred for 2 hr. at 9° and for a further 2 hr. at room temperature. To the light yellow mixture was then added, in one portion, a solution of 22.4 g of crude (20S)-1α,3β-bis[(tetrahydro-2H-pyran-2-yl)oxy]-20-methyl-21-p-toluenesulfonyloxypregn-5-ene (corresponding to approximately 0.033 mol), in 40 ml of dioxane and stirred for 64 hr. at 105° under argon. The mixture, which became dark yellow and cloudy, was cooled to room temperature, poured onto 500 g of ice, and the emulsion was extracted 3 times with 200 ml of ether. The ether extracts were washed successively 2 times with 200 ml of water, combined, dried over sodium sulfate and concentrated under vacuum at 40°. The residue was dissolved in 200 ml of toluene and concentrated under vacuum at 40°. The residue was treated twice more in the same way to remove dioxane and excess 3-methyl-3[(tetrahydro-2H-pyran-2-yl)oxy]-but-1-yne). After drying for 1 hr. under vacuum at room temperature, the remaining light brown oil, 34.1 g (which contained some 3-methyl-3[(tetrahydro-2H-pyran-2-yl)oxy]-but-1-yne and ditetrahydropyranyloxytosylate), was dissolved in ether and added to a column prepared with hexane--ether (9:1), containing 4 ml of pyridine/1, and 1 kg of silica gel. Elution with hexane--ether (4:1) mixtures (without the addition of pyridine) yielded 19.6 g (88%) of 1α,3β,25-tris[(tetrahydro-2H-pyran-2-yl)oxy]-cholest-5-en-23-yne.

Provenance & Evidence