Methyl iodide → HCID 57799920, compound

HRID 2100651Notes

Reaction equation

HRID 2100651 reaction equation
CN([CH2:4][CH:5]([CH:15]([C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[C:29]=1[CH3:35])[C:16](=[CH2:27])[C:17]([C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([O:25][CH3:26])[CH:20]=1)=[O:18])[C:6]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[F:14])=[O:7])C.IC.C(N(C(C)C)CC)(C)C.[OH-].[K+]>C(#N)C>[F:34][C:30]1[C:29]([CH3:35])=[C:28]([CH:15]([C:16](=[CH2:27])[C:17]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([O:25][CH3:26])[CH:20]=2)=[O:18])[C:5](=[CH2:4])[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[F:14])=[O:7])[CH:33]=[CH:32][CH:31]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 14797Potassium HydroxideHCID 81531DiisopropylethylamineHCID 57799941HCID 57799941, compound

Product 1

HCID 57799920HCID 57799920, compoundYield 47.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of crude 2-((dimethylamino)methyl)-3-(3-fluoro-2-methylphenyl)-1-(2-fluorophenyl)-5-(3-methoxyphenyl)-4-methylenepentane-1,5-dione (7.5 g, 15.7 mmol) in acetonitrile (60 mL) was added iodomethane (11.7 mL, 187 mmol) and diisopropylethylamine (5.4 mL, 31.3 mmol). The mixture was stirred at room temperature for 2 h, during which time a precipitate formed. To this heterogeneous mixture was added 2 M KOH (26 mL, 52 mmol), and the resulting mixture was refluxed for 6 h and then allowed to stand for 48 h. The mixture was partitioned between dichloromethane and water. The layers were separated and the aqueous phase extracted twice with dichloromethane. The combined organic layers were dried over MgSO4 and evaporated to dryness. The residue was purified over silica gel using 30% EtOAc/hexanes to give 3-(3-fluoro-2-methylphenyl)-1-(2-fluorophenyl)-5-(3-methoxyphenyl)-2,4-dimethylenepentane-1,5-dione (3.2 g, 47% yield), (characterized by LCMS and 1H NMR), LRMS (M+H+) m/z=433.4.

Workup

  1. customformed
  2. temperaturethe resulting mixture was refluxed for 6 h
  3. waitto stand for 48 h
  4. customThe mixture was partitioned between dichloromethane and water
  5. customThe layers were separated
  6. extractionthe aqueous phase extracted twice with dichloromethane
  7. dry with materialThe combined organic layers were dried over MgSO4
  8. customevaporated to dryness
  9. customThe residue was purified over silica gel using 30% EtOAc/hexanes

Sources & evidence

ORD record
ord-e68bc5a2c2ce4fc3a960041b8a41ad8c
Source dataset
uspto-grants-2009_08
Patent number
US07572814B2

Reaction notes

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