3-Bromoanisole → (2,4-Difluoro-phenyl)-(3-methoxy-phenyl)-methanol

HRID 852076Notes

Reaction equation

HRID 852076 reaction equation
C([Li])CCC.Br[C:7]1[CH:8]=[C:9]([O:13][CH3:14])[CH:10]=[CH:11][CH:12]=1.[F:15][C:16]1[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:17]=1[CH:18]=[O:19]>O1CCCC1>[F:15][C:16]1[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:17]=1[CH:18]([C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][CH3:14])[CH:8]=1)[OH:19]

Participants

5

Reactant 3

HCID 169713-BromoanisoleHCID 737702,4-DifluorobenzaldehydeHCID 178418339Butyllithium

Product 1

HCID 17906348(2,4-Difluoro-phenyl)-(3-methoxy-phenyl)-methanolYield 102.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Add n-butyl lithium solution (2.5 M, 140 mL, 350 mmol) to 3-bromoanisole (44.6 mL, 352.2 mmol) in cold (−78° C.) tetrahydrofuran (anhydrous, 500 mL), dropwise. Let stir for 10 minutes and add 2,4 difluorobenzaldehyde (50 g, 351 mmol), dropwise, and stir for an additional 1 hour. After 1 hour the reaction is complete. Quench the reaction mixture with cold water, extract with ethyl acetate, dry (MgSO4), and concentrate to give the crude, title compound (Compound 7) (90.21 g, >100% Yield). Use compound in a crude form or purify by column chromatography (20% ethyl acetate in heptane). NMR agrees with the final, desired compound.

Workup

  1. stirringdropwise, and stir for an additional 1 hour
  2. waitAfter 1 hour the reaction is complete
  3. customQuench the reaction mixture with cold water
  4. extractionextract with ethyl acetate
  5. dry with materialdry (MgSO4)
  6. concentrationconcentrate

Sources & evidence

ORD record
ord-6ef3eac10bf24569bd497107359035e9
Source dataset
uspto-grants-2007_08
Patent number
US07253165B2

Reaction notes

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