Methanol → Cyclopropyl[4-(trifluoromethoxy)phenyl]methanone

HRID 1588885Notes

Reaction equation

HRID 1588885 reaction equation
[CH:1]1([Br:4])[CH2:3][CH2:2]1.[Mg:5].[F:6][C:7]([F:18])([F:17])[O:8][C:9]1[CH:16]=[CH:15][C:12]([C:13]#N)=[CH:11][CH:10]=1.C[OH:20]>O1CCCC1>[CH:15]1([Mg:5][Br:4])[CH2:12][CH2:11]1.[F:6][C:7]([F:18])([F:17])[O:8][C:9]1[CH:16]=[CH:15][C:12]([C:13]([CH:1]2[CH2:3][CH2:2]2)=[O:20])=[CH:11][CH:10]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 676214-(Trifluoromethoxy)benzonitrileHCID 78037BromocyclopropaneHCID 5462224Magnesium

Product 2

HCID 15042027Cyclopropyl[4-(trifluoromethoxy)phenyl]methanoneHCID 178418630HCID 178418630, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Cyclopropylmagnesium bromide was prepared by adding 3.3 grams (0.11 mole) of cyclopropyl bromide to 2.9 grams (0.12 mole) of magnesium in refluxing tetrahydrofuran. Upon completion of addition, the Grignard reagent was stirred at reflux for one hour and then was cooled to ambient temperature. To this was added dropwise a solution of 20.5 grams (0.11 mole) of 4-trifluoromethoxybenzonitrile in tetrahydrofuran. Upon completion of addition, the reaction mixture was warmed to a temperature just below reflux at which temperature it was stirred for about 18 hours. The reaction mixture was cooled to ambient temperature, and 40 ml of methanol was added dropwise. Upon completion of addition, the reaction mixture was stirred for two hours and then was filtered. The filtrate was stirred for about 60 hours with about 25 grams of silica gel and 100 ml of water. The mixture was filtered, and the filtrate was diluted with ethyl acetate. The mixture was washed with water, and the organic layer was dried with magnesium sulfate. The mixture was then filtered, and the filtrate was concentrated under reduced pressure, yielding 12.4 grams of cyclopropyl 4-trifluoromethoxyphenyl ketone.

Workup

  1. additionUpon completion of addition
  2. temperatureat reflux for one hour
  3. additionUpon completion of addition
  4. temperaturethe reaction mixture was warmed to a temperature just
  5. temperaturebelow reflux at which temperature it
  6. temperatureThe reaction mixture was cooled to ambient temperature
  7. additionUpon completion of addition
  8. stirringthe reaction mixture was stirred for two hours
  9. filtrationwas filtered
  10. stirringThe filtrate was stirred for about 60 hours with about 25 grams of silica gel and 100 ml of water
  11. filtrationThe mixture was filtered
  12. additionthe filtrate was diluted with ethyl acetate
  13. washThe mixture was washed with water
  14. dry with materialthe organic layer was dried with magnesium sulfate
  15. filtrationThe mixture was then filtered
  16. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-7d89936be1f0489e9331a846e16c536e
Source dataset
uspto-grants-1993_06
Patent number
US05223536

Reaction notes

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