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

HRID 2268336Notes

Reaction equation

[Si]([O:8][C@@H:9]1[C@@:28]2([CH3:29])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:27]2[CH2:26][CH2:25][C@@:24]2([CH3:30])[C@H:17]3[CH2:18][CH:19]=[C:20]2[C@@H:21]([OH:23])[CH3:22])[CH2:12][C@@H:11]([O:31][Si](C(C)(C)C)(C)C)[CH2:10]1)(C(C)(C)C)(C)C.CC(C)([O-])C.[K+].C1OCCOC2C(=CC=CC=2)OCCOCCOC2C(=CC=CC=2)OC1.[O:71]1[C@@H:73]([CH:74]([CH3:76])[CH3:75])[CH2:72]1.[Si](O[C@@H]1[C@@]2(C)C(=CC=C3[C@@H]2CC[C@@]2(C)[C@H]3CC=C2[C@@H](OC[C@@H](O)C(C)C)C)C[C@@H](O[Si](C(C)(C)C)(C)C)C1)(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1(C)C=CC=CC=1.C(OCC)C.O1CCCC1.C(OCC)(=O)C>[OH:8][C@@H:9]1[C@@:28]2([CH3:29])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:27]2[CH2:26][CH2:25][C@@:24]2([CH3:30])[C@H:17]3[CH2:18][CH:19]=[C:20]2[C@@H:21]([O:23][CH2:72][C@@H:73]([OH:71])[CH:74]([CH3:76])[CH3:75])[CH3:22])[CH2:12][C@@H:11]([OH:31])[CH2:10]1

Participants

Conditions

Temperature: 106 °C

Procedure

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-methylbutyloxy}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%).

Workup

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

Sources & evidence

ORD record: ord-2b8ebcc4a2a8458b92a4cc32c444a521
Source dataset: uspto-grants-2001_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06326503B1

Reaction notes

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