4-Bromo-3-fluorotoluene → 2'-Fluoro-4'-methylacetophenone

HRID 1792449Notes

Reaction equation

HRID 1792449 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[F:9].C([Sn](CCCC)(CCCC)[C:15]([O:17]CC)=[CH2:16])CCC>C1(C)C=CC=CC=1.C(OCC)(=O)C.[F-].[K+].[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:9][C:3]1[CH:4]=[C:5]([CH3:8])[CH:6]=[CH:7][C:2]=1[C:15](=[O:17])[CH3:16]

Participants

7

Reactant 2

HCID 5732804-Bromo-3-fluorotolueneHCID 619414Stannane, tributyl(1-ethoxyethenyl)-

Product 1

HCID 27784842'-Fluoro-4'-methylacetophenoneYield 114.5%

Reagents, catalysts & solvents 4

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolventHCID 522689Potassium FluorideSolvent

Procedure

54 mL solution of 5.0 g 1-bromo-2-fluoro-4-methylbenzene, 10 g tributyl(1-ethoxyvinyl)tin and 1.53 g tetrakis (triphenylphosphine) palladium in toluene was heated at 120° C. for 2 hours. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate, 10% aqueous potassium fluoride solution was added thereto and stirred for 30 minutes, and formed insolubles were filtered off through Celite. The organic layer was washed with water, then hydrolyzed by vigorously stirring it together with 5 N aqueous hydrochloric acid, and the organic layer was further washed with water and brine. The solution was dried over anhydrous sodium sulfate, then the solvent was removed, and the resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give 4.61 g of 2′-fluoro-4′-methylacetophenone (yellow oil) as a crude product. From 4.61 g crude 2′-fluoro-4′-methylacetophenone, 4.1 g of the title compound (yellow oil) was obtained by the same method as in Production Example 3.

Workup

  1. additionwas added
  2. customformed insolubles
  3. filtrationwere filtered off through Celite
  4. washThe organic layer was washed with water
  5. stirringby vigorously stirring it together with 5 N aqueous hydrochloric acid
  6. washthe organic layer was further washed with water and brine
  7. dry with materialThe solution was dried over anhydrous sodium sulfate
  8. customthe solvent was removed
  9. customthe resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-7e06764fbfd84dcfb07798a6103e3bba
Source dataset
uspto-grants-2006_07
Patent number
US07074801B1

Reaction notes

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