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

HRID 496856Notes

Reaction equation

HRID 496856 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>[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

7

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 2

HCID 807IodineCatalystHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
30 °C

Procedure

Under a nitrogen atmosphere, turnings of magnesium (16.8 g) were dispersed in THF (116 ml), and iodine (0.1 g) was added. Under a nitrogen atmosphere, a solution of 4-bromofluorobenzene (116 g) in THF (201 ml) was added dropwise at 15-40° C., and the mixture was stirred at 20-40° C. for 2 hr. The obtained mixture with a Grignard reagent was cooled and thereto was added dropwise a solution of 2,4-dimethylbenzaldehyde (81 g) in THF (81 ml) at 0-20° C. After the dropwise addition, the reaction mixture was stirred at 0-20° C. for 2 hr. A saturated aqueous ammonium chloride solution was added to stop the reaction. The reaction mixture was partitioned and the obtained organic layer was retained. The aqueous layer was extracted with toluene and combined with the organic layer obtained earlier, and 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.

Workup

  1. additionAfter the dropwise addition
  2. stirringthe reaction mixture was stirred at 0-20° C. for 2 hr
  3. customthe reaction
  4. customThe reaction mixture was partitioned
  5. extractionThe aqueous layer was extracted with toluene
  6. customobtained earlier
  7. washwashed with saturated brine
  8. customThe solvent was evaporated from the organic layer under reduced pressure

Sources & evidence

ORD record
ord-7bdbcf14cc63450695f7b7f76c3e4b9a
Source dataset
uspto-grants-2005_09
Patent number
US06946564B2

Reaction notes

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