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

HRID 1817841Notes

Reaction equation

HRID 1817841 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([F:15])([F:14])[C:10]([F:13])([F:12])[F:11])=[CH:5][CH:4]=1.[Li]CCCC.[C:21](Cl)(=[O:23])[CH3:22]>C1COCC1.CCCCCC.CCOCC.[Cl-].[Zn+2].[Cl-]>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]([F:14])([F:15])[C:10]([F:11])([F:12])[F:13])=[CH:7][C:8]=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

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

Workup

  1. waitfor 45 minutes at 0° C
  2. stirringAfter stirring for 10 minutes at 0° C.
  3. customThe medium is then deoxygenated with nitrogen and 332 mg of benzyl(chloro)bis(triphenylphosphine)-palladium in 5 mL of anhydrous THF
  4. additionare introduced
  5. stirringThe medium is stirred for 2 hours 30 minutes at 0° C.
  6. waitfor 72 hours at RT
  7. additionThe medium is poured onto a 2.5 M HCl solution
  8. extractionextracted with ether
  9. washThe organic phase is washed with 5% NaHCO3 in water, with water
  10. dry with materialAfter drying over MgSO4 and evaporation
  11. customthe crude product is purified by flash chromatography on silica

Sources & evidence

ORD record
ord-8e071a764bfe46a4a07ec5062e2c8b3a
Source dataset
uspto-grants-2009_10
Patent number
US07598392B2

Reaction notes

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