Methane → 2-(2,4-Difluoro-phenyl)-6-methoxy-naphthalene-1-carbaldehyde

HRID 1513973Notes

Reaction equation

HRID 1513973 reaction equation
[CH:1]([C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:13][CH3:14])=[CH:10][CH:11]=2)[CH:6]=[CH:5][C:4]=1OS(C(F)(F)F)(=O)=O)=[O:2].[F-].[Cs+].[F:25][C:26]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:27]=1B(O)O.C>C(#N)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:25][C:26]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:27]=1[C:4]1[CH:5]=[CH:6][C:7]2[C:12](=[CH:11][CH:10]=[C:9]([O:13][CH3:14])[CH:8]=2)[C:3]=1[CH:1]=[O:2]

Participants

7

Reactant 4

HCID 297MethaneHCID 25953Cesium fluorideHCID 27343342,4-Difluorophenylboronic acidHCID 86626531Trifluoromethanesulfonic acid 1-formyl-6-methoxy-naphthalen-2-yl ester

Product 1

HCID 575525532-(2,4-Difluoro-phenyl)-6-methoxy-naphthalene-1-carbaldehydeYield 62%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolvent

Procedure

Combine trifluoromethanesulfonic acid 1-formyl-6-methoxy-naphthalen-2-yl ester (2.53 g, 7.6 mmol) with dichlorobis(triphenylphosphine)palladium (II) (0.53 g, 0.8 mmol), cesium fluoride (5.75 g, 37.8 mmol), and 2,4-difluorophenylboronic acid (2.39 g, 15.1 mmol) in acetonitrile (25 mL). Heat to reflux for 1 hour. Cool to room temperature, add DARCO, and filter. Concentrate in vacuo, dilute with dichloromethane and wash with saturated aqueous sodium carbonate. Dry the organic layer over magnesium sulfate, filter, add silica gel, and concentrate in vacuo. Purify the residue by column chromatography using an eluent of 1.5:1 hexanes:dichloromethane to give 1.4 g of the title compound (62%).

Workup

  1. temperatureHeat
  2. temperatureto reflux for 1 hour
  3. filtrationfilter
  4. concentrationConcentrate in vacuo
  5. additiondilute with dichloromethane
  6. washwash with saturated aqueous sodium carbonate
  7. dry with materialDry the organic layer over magnesium sulfate
  8. filtrationfilter
  9. additionadd silica gel
  10. concentrationconcentrate in vacuo
  11. customPurify the residue by column chromatography

Sources & evidence

ORD record
ord-082f5f66022d4158b9848a6aeb68f97b
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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