HCID 68973002, compound → HCID 68973350, compound

HRID 749051Notes

Reaction equation

HRID 749051 reaction equation
[CH3:1][Mg+].[Br-].[CH2:4]=[C:5]1[C:22]2[C@:17]([CH3:24])([CH2:18][CH2:19][C:20](=[O:23])[CH:21]=2)[C@@H:16]2[C@H:7]([C@H:8]3[C@@:12]([CH2:14][CH2:15]2)([CH3:13])[C@@H:11]([C:25]([NH:27][C:28]2[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=2)=[O:26])[CH2:10][CH2:9]3)[CH2:6]1>CCOCC.Cl[Cu]>[CH2:4]([C:5]1[CH2:6][C@@H:7]2[C@@H:16]([C@:17]3([CH3:24])[C:22]=1[CH2:21][C:20](=[O:23])[CH2:19][CH2:18]3)[CH2:15][CH2:14][C@@:12]1([CH3:13])[C@H:8]2[CH2:9][CH2:10][C@@H:11]1[C:25]([NH:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]([F:36])([F:35])[F:37])=[CH:30][CH:29]=1)=[O:26])[CH3:1]

Participants

5

Reactant 2

HCID 68973002HCID 68973002, compoundHCID 178418689HCID 178418689, compound

Product 1

HCID 68973350HCID 68973350, compound

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3.0 M MeMgBr (0.36 mL, 1.09 mmol) in ether under N2 was added 2.2 mL Argon-purged, anhydrous THF. The mixture was cooled to 0° C. CuCl (0.014 g, 0.14 mmol) was added, and the reaction was stirred for 5 min before adding (17β)-6-methylene-3-oxo-N-[4-(trifluoromethyl)phenyl]androst-4-ene-17-carboxamide (3-4) (0.12 g, 0.25 mmol) as a solid. After several hours the reaction was quenched by dropwise addition of 5.0 mL of Ar-purged water, then partitioned between CHCl3 and 10% KHSO4 solution. The organic phase was washed with saturated NaHCO3 solution and brine, then dried with MgSO4 and concentrated. The residue was purified by flash silica gel chromatography (0 to 30% EtOAc/hexane) and concentrated to yield a clear, colorless oil, which was further purified by preparative HPLC (C18; 70% MeOH with 5 to 30% MeCN-water) to provide the desired product.

Workup

  1. custompurged
  2. customAfter several hours the reaction was quenched by dropwise addition of 5.0 mL of Ar-purged water
  3. custompartitioned between CHCl3 and 10% KHSO4 solution
  4. washThe organic phase was washed with saturated NaHCO3 solution and brine
  5. dry with materialdried with MgSO4
  6. concentrationconcentrated
  7. customThe residue was purified by flash silica gel chromatography (0 to 30% EtOAc/hexane)
  8. concentrationconcentrated
  9. customto yield a clear, colorless oil, which
  10. customwas further purified by preparative HPLC (C18; 70% MeOH with 5 to 30% MeCN-water)

Sources & evidence

ORD record
ord-b8b6606bac3f48149524766b43e846bd
Source dataset
uspto-grants-2008_07
Patent number
US07402577B2

Reaction notes

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