Dimethylformamide → 2,6-Difluoro-3-(phenylmethoxy)benzaldehyde

HRID 253379Notes

Reaction equation

HRID 253379 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=1[F:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:17](=O)=[O:18].CC(C)=O.C([Li])CCC.CN(C)C=O>O1CCCC1.O>[CH2:1]([O:8][C:9]1[C:10]([F:16])=[C:11]([C:12]([F:15])=[CH:13][CH:14]=1)[CH:17]=[O:18])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 5612691-(benzyloxy)-2,4-difluorobenzeneHCID 18522661Acetone cardiceHCID 178418339Butyllithium

Product 1

HCID 5613532,6-Difluoro-3-(phenylmethoxy)benzaldehydeYield 74%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To 1-Benzyloxy-2,4-difluoro-benzene (26, 3.00 g, 13.6 mmol) in tetrahydrofuran (48 mL) under an atmosphere of nitrogen and cooled with dry ice/acetone was added n-butyllithium (1.60 M in hexane, 8.94 mL). After 20 minutes, N,N-dimethylformamide (1.46 mL, 0.0189 mol) was added to the reaction. After another 20 minutes, the flask was stirred at room temperature for 30 minutes. The reaction mixture was poured into water, acidified to pH=1, and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, concentrated and purified with silica gel column chromatography eluting with 30% ethyl acetate in hexane to give the compound as a yellow solid (27, 2.5 g, 74%).

Workup

  1. waitAfter another 20 minutes
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. custompurified with silica gel column chromatography
  7. washeluting with 30% ethyl acetate in hexane

Sources & evidence

ORD record
ord-21a35022675c40b89dcccb96ddfac6e5
Source dataset
uspto-grants-2011_01
Patent number
US07872018B2

Reaction notes

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