Diisopropylamine → Ethyl 3-cyclopropyl-3-(4-trifluoromethylphenyl)propenoate

HRID 1588883Notes

Reaction equation

HRID 1588883 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.C[Si]([CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])(C)C.[F:23][C:24]([F:37])([F:36])[C:25]1[CH:30]=[CH:29][C:28]([C:31]([CH:33]2[CH2:35][CH2:34]2)=O)=[CH:27][CH:26]=1>O1CCCC1.CCCCCC>[CH:33]1([C:31]([C:28]2[CH:29]=[CH:30][C:25]([C:24]([F:23])([F:36])[F:37])=[CH:26][CH:27]=2)=[CH:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:35][CH2:34]1

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 77687Ethyl trimethylsilylacetateHCID 11171894Cyclopropyl 4-trifluoromethylphenyl ketoneHCID 178418339Butyllithium

Product 1

HCID 54171653Ethyl 3-cyclopropyl-3-(4-trifluoromethylphenyl)propenoateYield 52.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

A stirred solution of 4.1 grams (0.04 mole) of diisopropylamine in 100 ml of tetrahydrofuran was cooled to -78° C., and 17.4 ml (0.04 mole) of 2.3 M n-butyllithium in hexane was added during a 15 minute period. Upon completion of addition, the reaction mixture was stirred at -78° C. for 15 minutes. After this time, 6.4 grams (0.04 mole) of ethyl (trimethylsilyl)acetate was added during a 10 minute period. Upon completion of addition, the reaction mixture was stirred at -78° C. for 30 minutes, and 8.5 grams (0.04 mole) of cyclopropyl (4-trifluoromethylphenyl) ketone was added during a 5 minute period. After this time the reaction mixture was stirred at -78° C. for one hour, at -25° C. for one hour, and finally at ambient temperature for two hours. The reaction was then quenched with aqueous 5% hydrochloric acid. The mixture was then extracted with diethyl ether, and the combined extracts were dried with sodium sulfate. The mixture was filtered, and the filtrate was concentrated under reduced pressure to a residue. The residue was subjected to column chromatography on silica gel. Elution was accomplished using 5% diethyl ether in hexane. The appropriate fractions were combined and concentrated under reduced pressure, yielding 6.0 grams of ethyl 3-cyclopropyl-3-(4-trifluoromethylphenyl)propenoate. The nmr spectrum was consistent with the proposed structure.

Workup

  1. additionUpon completion of addition
  2. additionUpon completion of addition
  3. stirringthe reaction mixture was stirred at -78° C. for 30 minutes
  4. stirringAfter this time the reaction mixture was stirred at -78° C. for one hour, at -25° C. for one hour
  5. waitfinally at ambient temperature for two hours
  6. customThe reaction was then quenched with aqueous 5% hydrochloric acid
  7. extractionThe mixture was then extracted with diethyl ether
  8. dry with materialthe combined extracts were dried with sodium sulfate
  9. filtrationThe mixture was filtered
  10. concentrationthe filtrate was concentrated under reduced pressure to a residue
  11. washElution
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-0776d1f93e884473acc136a10aa07396
Source dataset
uspto-grants-1993_06
Patent number
US05223536

Reaction notes

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