Methanol → Methyl 2-fluoro-5-formylbenzoate

HRID 551972Notes

Reaction equation

HRID 551972 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[F:10])[CH:5]=[O:6].[CH3:11][OH:12].CN([CH:16]=[O:17])C>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:10][C:9]1[CH:8]=[CH:7][C:4]([CH:5]=[O:6])=[CH:3][C:2]=1[C:11]([O:17][CH3:16])=[O:12]

Participants

6

Reactant 3

HCID 887MethanolHCID 6228DimethylformamideHCID 1736043-Bromo-4-fluorobenzaldehyde

Product 1

HCID 24971957Methyl 2-fluoro-5-formylbenzoateYield 23%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)Catalyst

Conditions

Temperature
60 °C

Procedure

To a solution of 3-bromo-4-fluoro benzaldehyde (Aldrich, 10 g, 0.049 mol) in dry DMF (25 mL) was added dry methanol (40 mL) followed by TEA (9.9 g, 0.0988 mol), dppf (Aldrich, 1.36 g, 0.00246 mol) and palladium acetate (Aldrich, 0.31 g, 0.00138 mol). The reaction mixture was heated to 60° C. under carbon monoxide atmosphere for 20 h. The reaction mixture was cooled and purged with nitrogen to remove dissolved carbon monoxide if any. The solvent was removed under vacuum and the residue was purified by flash chromatography using silicagel (petrol ether/ ethyl acetate, 9:1) to afford 2 g (23%) of the title compound as a solid along with 6 g of unreacted starting material. TLC: Petrol ether/EtOAc (7:3); Rf=0.7; HPLC: purity >98%. 1H NMR (DMSO) δ: 10.04 (s, 1H), 8.45 (m, 1H), 8.20 (m, 1H), 7.59 (m, 1H), 3.90 (s, 3H).

Workup

  1. temperatureThe reaction mixture was cooled
  2. custompurged with nitrogen
  3. customto remove
  4. dissolutiondissolved carbon monoxide if any
  5. customThe solvent was removed under vacuum
  6. customthe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-4bbab4d75ec1485db6a23255a9bb2d21
Source dataset
uspto-grants-2011_05
Patent number
US07947851B2

Reaction notes

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