Dibenzo-18-crown-6 → 1alpha,3beta-dihydroxy-20(S)-{2(S)-hydroxy-3-methylbutyloxy}pregna-5,7,16-triene

Temperature

106 °C

To a solution of 1α,3β-bis(tert-butyldimethylsilyloxy)-20(S)-hydroxypregna-5,7,16-triene (97.9 mg, 0.175 mmol), potassium t-butoxide (230 mg, 2.05 mmol) and dibenzo-18-crown-6 (45.0 mg, 0.125 mmol) in toluene (6 ml) was added (S)-(+)-1,2-epoxy-3-methylbutane (0.18 ml, 1.72 mmol) at room temperature and the mixted solution was stirred at 106° C. for one hour. The reaction solution was diluted with diethyl ether and washed with brine, and then the organic layer was dried over magnesium sulfate. The solvent was distilled off under reduced pressure and the resulting residue was separated by preparative thin layer chromatography (0.5 mm×4, hexane:dichloromethane:ethyl acetate=45:5:2, developed three times) to give a fraction containing 1α,3β-bis(tert-butyldimethylsilyloxy)-20(S)-{2(S)-hydroxy-3-methyl-butyloxy}pregna-5,7,16-triene (67.5 mg). An aliquot of 52.6 mg was dissolved in tetrahydrofuran (1.5 ml) and stirred with 1M tetra-n-butylammonium fluoride solution in tetrahydrofuran (0.5 ml) under the condition of an outer temperature of 71° C. for 10 hours. After completion of the reaction, the reaction solution was diluted with ethyl acetate and washed with 1N hydrochloric acid, saturated aqueous sodium bicarbonate solution and brine successively, and the organic layer was dried over magnesium sulfate. The solvent was distilled off under reduced pressure and the resulting residue was purified by preparative thin layer chromatography (0.25 mm×2, dichloromethane:ethanol 15:1, developed twice) to give the title compound as a colorless oil (20.6 mg, 36%).

1. washwashed with brine
2. dry with materialthe organic layer was dried over magnesium sulfate
3. distillationThe solvent was distilled off under reduced pressure
4. customthe resulting residue was separated by preparative thin layer chromatography (0.5 mm×4, hexane:dichloromethane:ethyl acetate=45:5:2, developed three times)
5. customto give a fraction
6. customAfter completion of the reaction
7. washwashed with 1N hydrochloric acid, saturated aqueous sodium bicarbonate solution and brine successively
8. dry with materialthe organic layer was dried over magnesium sulfate
9. distillationThe solvent was distilled off under reduced pressure
10. customthe resulting residue was purified by preparative thin layer chromatography (0.25 mm×2, dichloromethane:ethanol 15:1

ORD record

ord-67bf3ba7e5284d66838fce04279e1dfd

Source dataset

uspto-grants-2001_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06184398B2