1-Chloro-4-(chloromethyl)benzene → 3-(4-Chlorophenyl)-1,1,1-trifluoropropan-2-one

HRID 484236Notes

Reaction equation

HRID 484236 reaction equation
[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6]Cl)=[CH:4][CH:3]=1.[Mg].[F:11][C:12]([F:19])([F:18])[C:13](OCC)=[O:14].CC(C)=O.C(=O)=O>CCOCC>[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][C:13](=[O:14])[C:12]([F:19])([F:18])[F:11])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 77231-Chloro-4-(chloromethyl)benzeneHCID 9794Ethyl trifluoroacetateHCID 5462224MagnesiumHCID 18522661Acetone cardice

Product 1

HCID 151139833-(4-Chlorophenyl)-1,1,1-trifluoropropan-2-oneYield 47.4%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent3×

Conditions

Temperature
-10 °C

Procedure

A solution of p-chlorobenzyl chloride (80.5 g, 0.5 mol) and ether (150 mL) is slowly added to a vigorously stirred slurry of magnesium turnings (12.15 g, 0.5 mol) and ether (50 mL) over a 45 minute period. After the addition is complete, the reaction mixture is refluxed for 1/2 hour then cooled in an ice bath. The Grignard reagent is then added to a solution of ethyl trifluoroacetate (71.04 g, 0.5 mol) and ether (150 mL) at -60° to -70° C. (acetone-dry ice bath) over a 45 minute period. The cooling bath is removed and the reaction mixture is allowed to warm to -10° C. The reaction mixture is then quenched with saturated ammonium chloride solution and then acidified with 10% hydrochloric acid solution. The organic layer is separated, washed sequentially with water and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to obtain a liquid. Vacuum distillation of the liquid gives the title product as a clear liquid (52.8 g, bp 72°-74° C./34 mm, 47%).

Workup

  1. additionAfter the addition
  2. temperaturethe reaction mixture is refluxed for 1/2 hour
  3. temperaturethen cooled in an ice bath
  4. customThe cooling bath is removed
  5. customThe reaction mixture is then quenched with saturated ammonium chloride solution
  6. customThe organic layer is separated
  7. washwashed sequentially with water and brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated in vacuo
  10. customto obtain a liquid
  11. distillationVacuum distillation of the liquid

Sources & evidence

ORD record
ord-6f2cebc2778a437691e9781c4eb991a2
Source dataset
uspto-grants-1993_07
Patent number
US05229524

Reaction notes

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