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

HRID 1785621Notes

Reaction equation

HRID 1785621 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 for 30 minutes at −70° C. and then for 45 minutes at 0° C. 15.5 ml of a 1M 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 2.5M 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 purifed by flash chromatography on silica to give 2.25 g of a white solid. m.p.=47° C.

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 2.5M 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

Sources & evidence

ORD record
ord-90d7ef64429c415dae25b6d9e70f1340
Source dataset
uspto-grants-2009_03
Patent number
US07504511B2

Reaction notes

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