Ammonia → 11beta-Methyl 17beta-hydroxyestr-5(10)-en-3-one
Reaction equation
[Li].N.[Li].N.[CH3:5][C@H:6]1[CH2:23][C@@:21]2([CH3:22])[C@@H:17]([CH2:18][CH2:19][C@@H:20]2[OH:24])[C@H:16]2[C:7]1=[C:8]1[C:13]([CH2:14][CH2:15]2)=[CH:12][CH2:11][CH2:10][CH2:9]1.[Cl-].[NH4+].C([OH:31])(C)(C)C>C1COCC1>[CH3:5][C@H:6]1[CH2:23][C@@:21]2([CH3:22])[C@@H:17]([CH2:18][CH2:19][C@@H:20]2[OH:24])[C@H:16]2[C@H:7]1[C:8]1[CH2:9][CH2:10][C:11](=[O:31])[CH2:12][C:13]=1[CH2:14][CH2:15]2Participants
Reactant 6
Product 1
Reagents, catalysts & solvents 1
Procedure
Under an argon atmosphere, lithium wire (270 mg, 38.9 mmol), cut into small pieces, was added to anhydrous ammonia (200 mL) and stirred at reflux for 2 hr. The lithium/ammonia mixture was chilled to −78° C. and a THF solution of the dienone (5a, 4.03 g, 14.07 mmol) containing t-butanol (1.24 mL), was added over 15 min. The mixture was stirred at −78° C. for 15 min before excess of lithium was destroyed with isoprene (1.5 mL). The reaction was quenched by means of the addition of solid ammonium chloride (16 g, 296.3 mmol). Ammonia was allowed to evaporate under a constant stream of nitrogen. The THF layer was washed with H2O and brine. The aqueous washes were extracted with ether (2×200 mL). the combined organic extracts were dried over Na2SO4 and evaporation of the solvent gave 4.25 g of 6a as a white solid in 100% yield. NMR (300 MHz, CDCl3): δ 0.889 (s, 3H, C18-7CH3), 0.916 (d, 3H, C11β-CH3), and 3.655 (t, 1H, C17β-H) ppm.
Workup
- temperatureat reflux for 2 hr
- additionwas added over 15 min
- customwas destroyed with isoprene (1.5 mL)
- customto evaporate under a constant stream of nitrogen
- washThe THF layer was washed with H2O and brine
- extractionThe aqueous washes were extracted with ether (2×200 mL)
- dry with materialthe combined organic extracts were dried over Na2SO4 and evaporation of the solvent
Sources & evidence
- ORD record
- ord-a8f3622d17454de88e89e3f6d72195e8
- Source dataset
- uspto-grants-2010_10
- Patent number
- US07820642B2
Reaction notes
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