4-Bromo-2-fluorobenzaldehyde → (4-Bromo-2-fluorophenyl)(2-(diethoxymethyl)phenyl)methanol

HRID 475424Notes

Reaction equation

HRID 475424 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]([O:12][CH2:13][CH3:14])[O:9][CH2:10][CH3:11].C([Li])CCC.[Br:20][C:21]1[CH:28]=[CH:27][C:24]([CH:25]=[O:26])=[C:23]([F:29])[CH:22]=1>C(OCC)C>[Br:20][C:21]1[CH:28]=[CH:27][C:24]([CH:25]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[CH:8]([O:12][CH2:13][CH3:14])[O:9][CH2:10][CH3:11])[OH:26])=[C:23]([F:29])[CH:22]=1

Participants

5

Reactant 3

HCID 1435174-Bromo-2-fluorobenzaldehydeHCID 34827781-Bromo-2-(diethoxymethyl)benzeneHCID 178418339Butyllithium

Product 1

HCID 66847952(4-Bromo-2-fluorophenyl)(2-(diethoxymethyl)phenyl)methanol

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

To a mechanically stirred solution of 1-bromo-2-(diethoxymethyl)benzene (266 g) in dry diethyl ether (1.5 ) cooled to −70° C. under nitrogen was added a 2.5M solution of n-butyl lithium in hexanes (414 mL) dropwise over 30 min. The reaction mixture was stirred at a temperature less than −60° C. for 45 min then a solution of 4-bromo-2-fluorobenzaldehyde in dry diethyl ether (1.5 ) was added dropwise over 1 h maintaining the low temperature. The cooling bath was removed allowing the reaction to warm to +10° C. over 3 h. The reaction was quenched by the addition of water (500 mL). Organic layer was separated and the aqueous layer washed with ethyl acetate (2×500 mL). Combined organic layers were washed with brine then dried over anhydrous sodium sulfate and evaporated to yield the title product (371.1 g) as a yellow oil.

Workup

  1. temperaturemaintaining the low temperature
  2. customThe cooling bath was removed
  3. customthe reaction
  4. temperatureto warm to +10° C. over 3 h
  5. customThe reaction was quenched by the addition of water (500 mL)
  6. customOrganic layer was separated
  7. washthe aqueous layer washed with ethyl acetate (2×500 mL)
  8. washCombined organic layers were washed with brine
  9. dry with materialthen dried over anhydrous sodium sulfate
  10. customevaporated

Sources & evidence

ORD record
ord-235b5db6609140bab5613b05b1f83379
Source dataset
uspto-grants-2014_01
Patent number
US08637551B2

Reaction notes

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