Toluene → 4-Methyl-1-(4-(trifluoromethyl)phenyl)pentan-1-one

HRID 220737

Reaction equation

HRID 220737 reaction equation
[Mg].[CH2:2]1[CH2:6][O:5][CH2:4][CH2:3]1.BrCCCCC.[F:13][C:14]([F:24])([F:23])[C:15]1[CH:22]=[CH:21]C(C#N)=CC=1.[C:25]1([CH3:31])[CH:30]=CC=[CH:27][CH:26]=1>O>[CH3:30][CH:25]([CH3:31])[CH2:26][CH2:27][C:4]([C:3]1[CH:21]=[CH:22][C:15]([C:14]([F:13])([F:23])[F:24])=[CH:6][CH:2]=1)=[O:5]

Participants

7

Reactant 5

HCID 1140TolueneHCID 8028TetrahydrofuranHCID 80571-Bromopentane2×HCID 67995Benzonitrile, 4-(trifluoromethyl)-HCID 5462224Magnesium

Product 1

HCID 469413964-Methyl-1-(4-(trifluoromethyl)phenyl)pentan-1-one

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Magnesium (17 g) was stirred 10 min under nitrogen then THF (400 mL) was added. 1-Bromo-4 -methylbutane (5 mL) was added and the mixture stirred 5 min until the reaction initiated (exotherm) the reminder of the bromomethylbutane (100 g, 0.672 mol) was added keeping the temp below 35° C. (water bath). The mixture was stirred 1 hr at RT and a solution of 4-trifluoromethylbenzonitrile (100 g, 0.584 mol) in toluene (1 L) containing some CuBr was added dropwise keeping the temp 25° C. The solution was stirred 1 h and quenched carefully with 15% H2SO4 (exotherm). The organic layer was decanted, washed with brine, dried over (MgSO4) and concentrated in vacuo. The oil was purified by column chromatography on silica using isohexane as eluant to give 4-methyl-1-[4-(trifluoromethyl)phenyl]pentan-1-one (126 g) which solidified on standing. 1H NMR δ (ppm)(CDCl3): 8.06 (2H, d, J 8.1 Hz), 7.73 (2H, d, J 8.1 Hz), 2.99 (2H, app. t, J 7.4 Hz), 1.68-1.60 (3H, m), 0.96 (6H, d, J 6.3 Hz).

Workup

  1. additionwas added
  2. stirringThe mixture was stirred 1 hr at RT
  3. additionwas added dropwise
  4. customthe temp 25° C
  5. stirringThe solution was stirred 1 h
  6. customquenched carefully with 15% H2SO4 (exotherm)
  7. customThe organic layer was decanted
  8. washwashed with brine
  9. dry with materialdried over (MgSO4)
  10. concentrationconcentrated in vacuo
  11. customThe oil was purified by column chromatography on silica

Sources & evidence

ORD record
ord-2abcdfc4e3864f97a79dfbc0f8bf4cac
Source dataset
uspto-grants-2012_06
Patent number
US08203004B2

Linked notes

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