Acetyl chloride → N-[2-(4-Acetyl-phenyl)-1,1-dimethyl-ethyl]-2,2,2-trifluoroacetamide

HRID 49384Notes

Reaction equation

HRID 49384 reaction equation
[CH3:1][C:2]([NH:11][C:12](=[O:17])[C:13]([F:16])([F:15])[F:14])([CH3:10])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[C:18](Cl)(=[O:20])[CH3:19].[Cl-].[Al+3].[Cl-].[Cl-]>C(Cl)Cl>[C:18]([C:7]1[CH:8]=[CH:9][C:4]([CH2:3][C:2]([NH:11][C:12](=[O:17])[C:13]([F:16])([F:14])[F:15])([CH3:1])[CH3:10])=[CH:5][CH:6]=1)(=[O:20])[CH3:19]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 592937N-(1,1-Dimethyl-2-phenylethyl)-2,2,2-trifluoroacetamideHCID 6451240Aluminum(III) Chloride

Product 1

HCID 18532924N-[2-(4-Acetyl-phenyl)-1,1-dimethyl-ethyl]-2,2,2-trifluoroacetamideYield 99%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A flame-dried 250 ml flask was charged with N-(1,1-dimethyl-2-phenyl-ethyl)-2,2,2-trifluoroacetamide (5.93 g, 24.2 mmol), acetyl chloride (4.00 g, 55.6 mmol), and methylene chloride. The resulting solution was cooled to about 0° C., and aluminum (III) chloride (11.0 g, 82.2 mmol) was added in portions over about thirty minutes. Over the course of the addition, the solution changed from colorless to greenish-brown. After the addition was complete, the solution was heated to reflux for about thirty minutes, and was then cooled to room temperature and poured over 300 ml of ice water. After stirring for about ten minutes, the mixture was diluted with 125 ml of methylene chloride, and the layers were separated. The aqueous layer was extracted with an additional 125 ml of methylene chloride. The combined organic extracts were then washed with water and brine, sequentially, and then dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting oil, (6.9 g, 99% yield) which was ascertained to be about 85% pure by NMR, was carried into the subsequent reaction without further purification. LRMS ([M+1]+)=288.2.

Workup

  1. additionOver the course of the addition
  2. additionAfter the addition
  3. temperaturethe solution was heated
  4. temperatureto reflux for about thirty minutes
  5. temperaturewas then cooled to room temperature
  6. customthe layers were separated
  7. extractionThe aqueous layer was extracted with an additional 125 ml of methylene chloride
  8. washThe combined organic extracts were then washed with water and brine
  9. dry with materialsequentially, and then dried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customwas carried into the subsequent reaction without further purification

Sources & evidence

ORD record
ord-9ecab9f3e32243e9b32fbc095b4a5be1
Source dataset
uspto-grants-2004_03
Patent number
US06706743B2

Reaction notes

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