Acetyl chloride → 1-[2-Methoxy-5-(pentafluoroethyl)phenyl]ethanone

HRID 499219Notes

Reaction equation

HRID 499219 reaction equation
[Li]CCCC.[CH3:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]([F:20])([F:19])[C:15]([F:18])([F:17])[F:16])=[CH:10][CH:9]=1.[C:21](Cl)(=[O:23])[CH3:22]>CCCCCC.C1COCC1.CCOCC.[Cl-].[Zn+2].[Cl-]>[CH3:6][O:7][C:8]1[CH:9]=[CH:10][C:11]([C:14]([F:19])([F:20])[C:15]([F:16])([F:17])[F:18])=[CH:12][C:13]=1[C:21](=[O:23])[CH3:22]

Participants

8

Reactant 3

HCID 6367Acetyl chlorideHCID 128719661-Methoxy-4-(pentafluoroethyl)benzeneHCID 178418339Butyllithium

Product 1

HCID 860887051-[2-Methoxy-5-(pentafluoroethyl)phenyl]ethanone

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
-70 °C

Procedure

7.4 ml of BuLi at 2.5M in hexane are added, at −70° C., to a solution of 3.5 g of 1-methoxy-4-pentafluoroethylbenzene in 50 ml of anhydrous THF. The medium is stirred at −70° C. for 30 min and then at 0° C. for 45 min. 15.5 ml of a 1M solution of zinc chloride in ether are then added. After stirring at 0° C. for 10 min, 1.33 ml of acetyl chloride are added. The medium is then deoxygenated with nitrogen, and 332 mg of palladium benzyl(chloro)bis(triphenylphosphine) in 5 ml of anhydrous THF are introduced. The medium is stirred at 0° C. for 2 h 30 min and then at AT for 72 hours. The medium is run into a 2.5M HCl solution and then extracted in ether. The organic phase is washed with NaHCO3 at 5% in water, with water, and then with a saturated NaCl solution. After drying over MgSO4 and evaporation, the crude is purified by flash chromatography on silica, to give 2.25 g of a white solid.

Workup

  1. waitat 0° C. for 45 min
  2. stirringAfter stirring at 0° C. for 10 min
  3. customThe medium is then deoxygenated with nitrogen, and 332 mg of palladium benzyl(chloro)bis(triphenylphosphine) in 5 ml of anhydrous THF
  4. additionare introduced
  5. stirringThe medium is stirred at 0° C. for 2 h 30 min
  6. waitat AT for 72 hours
  7. extractionextracted in ether
  8. washThe organic phase is washed with NaHCO3 at 5% in water, with water
  9. dry with materialAfter drying over MgSO4 and evaporation
  10. customthe crude is purified by flash chromatography on silica

Sources & evidence

ORD record
ord-805ee1f399d941488a75e21c41053fe3
Source dataset
uspto-grants-2010_08
Patent number
US07767681B2

Reaction notes

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