1-Bromo-4-fluorobenzene → (2,4-Dimethylphenyl)(4-fluorophenyl)methanol

HRID 496858Notes

Reaction equation

HRID 496858 reaction equation
[Mg].Br[C:3]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][CH:4]=1.[CH3:10][C:11]1[CH:18]=[C:17]([CH3:19])[CH:16]=[CH:15][C:12]=1[CH:13]=[O:14].[Cl-].[NH4+]>C1COCC1.II.BrC1C=CC(F)=CC=1>[CH3:10][C:11]1[CH:18]=[C:17]([CH3:19])[CH:16]=[CH:15][C:12]=1[CH:13]([C:3]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][CH:4]=1)[OH:14]

Participants

8

Reactant 4

HCID 99931-Bromo-4-fluorobenzeneHCID 25517Ammonium ChlorideHCID 618142,4-DimethylbenzaldehydeHCID 5462224Magnesium

Product 1

HCID 9899421(2,4-Dimethylphenyl)(4-fluorophenyl)methanolYield 100.1%

Reagents, catalysts & solvents 3

HCID 807IodineCatalystHCID 99931-Bromo-4-fluorobenzeneCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
39 °C

Procedure

Under a nitrogen atmosphere, turnings of magnesium (16.8 g) were dispersed in THF (46 ml), and iodine (0.1 g) was added. Then, 4-bromofluorobenzene (2.1 g) was added dropwise. After confirmation of the start of the reaction, THF (242 ml) was flown in. 4-Bromofluorobenzene (113.9 g) was added dropwise at 31.8-48.9° C., and the mixture was stirred at 38-40° C. for 2 hr. The obtained mixture with a Grignard reagent was cooled and thereto was added dropwise 2,4-dimethylbenzaldehyde (81 g) at 5-29.9° C. After the dropwise addition, the reaction mixture was stirred at 21.3-28.3° C. for 1.5 hr. A saturated aqueous ammonium chloride solution was added to stop the reaction. The reaction mixture was partitioned and the obtained organic layer was washed with saturated brine. The solvent was evaporated from the organic layer under reduced pressure to give (2,4-dimethylphenyl)-(4′-fluorophenyl)methanol (139.2 g, 100%) as a colorless oil. The obtained colorless oil was measured for 1H-NMR and found to be the same as in Example 1.

Workup

  1. additionAfter the dropwise addition
  2. stirringthe reaction mixture was stirred at 21.3-28.3° C. for 1.5 hr
  3. customthe reaction
  4. customThe reaction mixture was partitioned
  5. washthe obtained organic layer was washed with saturated brine
  6. customThe solvent was evaporated from the organic layer under reduced pressure

Sources & evidence

ORD record
ord-82598bce4548443fa09c4fdf9dc166a9
Source dataset
uspto-grants-2005_09
Patent number
US06946564B2

Reaction notes

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