Hydrochloric Acid → Methyl 4-acetyl-2-fluorobenzoate

HRID 2245986Notes

Reaction equation

HRID 2245986 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([F:12])[CH:3]=1.[CH:13]([O:15]CCCC)=[CH2:14].C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+].Cl>CN(C=O)C.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:13]([C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([F:12])[CH:3]=1)(=[O:15])[CH3:14]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 8108Butyl vinyl etherHCID 11430Potassium CarbonateHCID 812191,3-Bis(diphenylphosphino)propaneHCID 113453114-Bromo-2-fluoro-benzoic acid methyl ester

Product 1

HCID 59216348Methyl 4-acetyl-2-fluorobenzoateYield 27.9%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of methyl 4-bromo-2-fluorobenzoate (7.0 g, 0.030 mol), 1-(ethenyloxy)butane (13 mL, 0.099 mol), palladium acetate (200 mg, 0.0009 mol), 1,3-bis(diphenylphosphino)propane (700 mg, 0.002 mol), and potassium carbonate (4.29 g, 0.0310 mol) in DMF (50 mL) and water (3 mL) was heated at 80° C. with stirring for 24 h. After cooling to RT, to the solution was added 1N HCl solution (31 ml). The mixture was stirred at RT for 1 h, and then extracted with ethyl ether. The combined extracts were washed with brine; dried over Na2SO4, filtered concentrated. The residue was flash chromatographed on a silica gel column to give the desired product (1.64 g).

Workup

  1. temperatureAfter cooling to RT, to the solution
  2. stirringThe mixture was stirred at RT for 1 h
  3. extractionextracted with ethyl ether
  4. washThe combined extracts were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customchromatographed on a silica gel column

Sources & evidence

ORD record
ord-77b9bb6b4ece45eb824ecbc8c4ffef90
Source dataset
uspto-grants-2010_03
Patent number
US07683060B2

Reaction notes

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