Sodium hydride → (1aS,5aR,7aS,8S,10cS)-5a,7a-dimethyl-3-oxo-N-phenyl-1,1a, 3,4,5,5a,5b,6,7,7a,8,9,10,10a,10b,10c-hexadecahydro-cyclopenta[a]cyclopropa[1]phenanthrene-8-carboxamide

HRID 749055Notes

Reaction equation

HRID 749055 reaction equation
[H-].[Na+].[I-].[CH3:4][S+](C)(C)=O.[O:9]=[C:10]1[CH2:27][CH2:26][C@@:25]2([CH3:28])[C:12]([CH:13]=[CH:14][C@@H:15]3[C@@H:24]2[CH2:23][CH2:22][C@@:20]2([CH3:21])[C@H:16]3[CH2:17][CH2:18][C@@H:19]2[C:29]([NH:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=2C(F)(F)F)=[O:30])=[CH:11]1>CS(C)=O>[CH3:28][C@:25]12[CH2:26][CH2:27][C:10](=[O:9])[CH:11]=[C:12]1[C@H:13]1[CH2:4][C@H:14]1[CH:15]1[CH:24]2[CH2:23][CH2:22][C@:20]2([CH3:21])[C@@H:19]([C:29]([NH:31][C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=3)=[O:30])[CH2:18][CH2:17][CH:16]21

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 68976085(17beta)-3-oxo-N-[2-(trifluoromethyl)phenyl]androsta-4,6-diene-17-carboxamide

Product 1

HCID 86594839(1aS,5aR,7aS,8S,10cS)-5a,7a-dimethyl-3-oxo-N-phenyl-1,1a, 3,4,5,5a,5b,6,7,7a,8,9,10,10a,10b,10c-hexadecahydro-cyclopenta[a]cyclopropa[1]phenanthrene-8-carboxamide

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

To a suspension of NaH (0.25 g, 6.18 mmol) in 7.4 mL DMSO (dried over molecular sieves) at room temperature under N2 was added trimethylsulfoxonium iodide (1.50 g, 6.85 mmol). The mixture was stirred for 1.5 hr. A solution of (17β)-3-oxo-N-[2-(trifluoromethyl)phenyl]androsta-4,6-diene-17-carboxamide (5-1) (0.68 g, 1.49 mmol) in 10 mL DMSO was added slowly. The solution was stirred at room temperature overnight. The reaction was then quenched by dropwise addition of 10% KHSO4 solution and extracted with CHCl3. The organic phase was washed with 10% KHSO4 solution, saturated NaHCO3 solution, and brine, then dried with MgSO4. After removal of the solvent, the residue was purified by chiral preparative HPLC (Chiralpak AD, 85% Hexanes (0.1% diethylamine); 15% 2-propanol) to yield the desired resolved products 6-6and 6-2.

Workup

  1. stirringThe solution was stirred at room temperature overnight
  2. customThe reaction was then quenched by dropwise addition of 10% KHSO4 solution
  3. extractionextracted with CHCl3
  4. washThe organic phase was washed with 10% KHSO4 solution, saturated NaHCO3 solution, and brine
  5. dry with materialdried with MgSO4
  6. customAfter removal of the solvent
  7. customthe residue was purified by chiral preparative HPLC (Chiralpak AD, 85% Hexanes (0.1% diethylamine); 15% 2-propanol)
  8. customto yield the

Sources & evidence

ORD record
ord-b1c40ff6d2a2459c9507307259a3d36a
Source dataset
uspto-grants-2008_07
Patent number
US07402577B2

Reaction notes

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