Water → (4-Fluoro-2-methylphenyl)(4-fluorophenyl)methanol

HRID 561420Notes

Reaction equation

HRID 561420 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH3:9].C([Li])CCC.[F:15][C:16]1[CH:23]=[CH:22][C:19]([CH:20]=[O:21])=[CH:18][CH:17]=1.O>O1CCCC1.CCCCCC.C(OCC)(=O)C>[F:8][C:5]1[CH:6]=[CH:7][C:2]([CH:20]([C:19]2[CH:22]=[CH:23][C:16]([F:15])=[CH:17][CH:18]=2)[OH:21])=[C:3]([CH3:9])[CH:4]=1

Participants

8

Reactant 4

HCID 962WaterHCID 680234-FluorobenzaldehydeHCID 967432-Bromo-5-fluorotolueneHCID 178418339Butyllithium

Product 1

HCID 58392149(4-Fluoro-2-methylphenyl)(4-fluorophenyl)methanol

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

1.00 g (5.29 mmol) of 2-bromo-5-fluorotoluene were dissolved in 10 ml of tetrahydrofuran at −78° C. Addition of 4.0 ml (6.35 mmol) of a 1.6N solution of n-butyllithium in hexane was followed by stirring for 15 min, and then 0.79 g (6.35 mmol) of p-fluorobenzaldehyde dissolved in 10 ml of tetrahydrofuran was added dropwise. The mixture was warmed to RT and stirred for 1 h. The reaction solution was mixed with water and ethyl acetate, and the phases were separated. The aqueous phase was extracted three times with ethyl acetate, and the combined organic phases were washed with saturated aqueous sodium chloride solution. The solvents were removed in vacuo, and the crude product was purified by preparative HPLC (mobile phase: acetonitrile-water gradient). 0.56 g (43% of theory) of the title compound was obtained.

Workup

  1. additionwas added dropwise
  2. stirringstirred for 1 h
  3. customthe phases were separated
  4. extractionThe aqueous phase was extracted three times with ethyl acetate
  5. washthe combined organic phases were washed with saturated aqueous sodium chloride solution
  6. customThe solvents were removed in vacuo
  7. customthe crude product was purified by preparative HPLC (mobile phase: acetonitrile-water gradient)

Sources & evidence

ORD record
ord-72a9b7629bdb48c7b48f8b0ed345465d
Source dataset
uspto-grants-2011_11
Patent number
US08063234B2

Reaction notes

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