1,1,1-Trifluoro-4-methylpent-3-en-2-one → 1,1,1-Trifluoro-4-(5-fluoro-2-methylphenyl)-4-methylpentan-2-one

HRID 2387293Notes

Reaction equation

HRID 2387293 reaction equation
[F:1][C:2]([F:10])([F:9])[C:3](=[O:8])[CH:4]=[C:5]([CH3:7])[CH3:6].[CH3:11][C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][C:13]=1[Mg]Br>C(OCC)C.[Cu]I>[F:1][C:2]([F:10])([F:9])[C:3](=[O:8])[CH2:4][C:5]([C:17]1[CH:16]=[C:15]([F:18])[CH:14]=[CH:13][C:12]=1[CH3:11])([CH3:7])[CH3:6]

Participants

5

Reactant 2

HCID 220326911,1,1-Trifluoro-4-methylpent-3-en-2-oneHCID 178426018HCID 178426018, compound

Product 1

HCID 207961201,1,1-Trifluoro-4-(5-fluoro-2-methylphenyl)-4-methylpentan-2-oneYield 80%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 3283Diethyl EtherSolvent

Procedure

To a slurry of 1,1,1-trifluoro-4-methylpent-3-en-2-one (49.5 g, 0.325 mol) and copper (I) iodide (61.9 g, 0.325 mol) in 700 mL of anhydrous diethyl ether at 0° C. was added a solution of 2-methyl-5-fluorophenyl magnesium bromide (0.5 M in THF, 706 mL, 0.353 mol) dropwise over 1.5 hours. The mixture was warmed to room temperature and stirred for a total of 18 hours. The reaction was quenched by addition of 500 mL of cold saturated ammonium chloride (NH4Cl) solution and the layers were separated. The aqueous layer was extracted with two 300 mL portions of diethyl ether. The combined organic fractions were washed with 300 mL of saturated ammonium chloride solution, three 300 mL portions of water and one 200 mL portion of brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. Purification by column chromatography with silica gel (eluted with hexanes) afforded 1,1,1-trifluoro-4-(5-fluoro-2-methylphenyl)-4-methylpentan-2-one (68.1 g, 80%).

Workup

  1. customThe reaction was quenched by addition of 500 mL of cold saturated ammonium chloride (NH4Cl) solution
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted with two 300 mL portions of diethyl ether
  4. washThe combined organic fractions were washed with 300 mL of saturated ammonium chloride solution, three 300 mL portions of water and one 200 mL portion of brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by column chromatography with silica gel (eluted with hexanes)

Sources & evidence

ORD record
ord-9f9722a076d943e8bc8c8480382d0ad3
Source dataset
uspto-grants-2012_09
Patent number
US08268859B2

Reaction notes

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