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

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.

1. customIn a 1.5 l 4-neck flask equipped with stirrer
2. waitat 9° and for a further 2 hr
3. customat room temperature
4. additionTo the light yellow mixture was then added, in one portion
5. customat 105°
6. extractionthe emulsion was extracted 3 times with 200 ml of ether
7. washThe ether extracts were washed successively 2 times with 200 ml of water
8. dry with materialdried over sodium sulfate
9. concentrationconcentrated under vacuum at 40°
10. dissolutionThe residue was dissolved in 200 ml of toluene
11. concentrationconcentrated under vacuum at 40°
12. additionThe residue was treated twice more in the same way
13. customto remove dioxane and excess 3-methyl-3[(tetrahydro-2H-pyran-2-yl)oxy]-but-1-yne)
14. customAfter drying for 1 hr
15. customat room temperature
16. dissolutionwas dissolved in ether
17. additionadded to a column
18. customprepared with hexane--ether (9:1)
19. washElution with hexane--ether (4:1) mixtures (
20. additionwithout the addition of pyridine)

ORD record

ord-08183ba155df469e97c573607cc8c0b7

Source dataset

uspto-grants-1982_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04310467