Acetophenone → Ethyl 3-(3-fluorophenyl)-3-oxopropanoate

HRID 1760343Notes

Reaction equation

HRID 1760343 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:5]=[C:6]([C:10](=[O:12])[CH3:11])[CH:7]=[CH:8][CH:9]=1.[H][H].C(C1C=CC=CC=1)(=O)C.[C:24](=O)([O:28]CC)[O:25][CH2:26][CH3:27]>CCCCCC>[CH2:26]([O:25][C:24](=[O:28])[CH2:11][C:10]([C:6]1[CH:7]=[CH:8][CH:9]=[C:4]([F:3])[CH:5]=1)=[O:12])[CH3:27]

Participants

7

Reactant 5

HCID 7410AcetophenoneHCID 7766Diethyl CarbonateHCID 99673-FluoroacetophenoneHCID 24758Sodium hydrideHCID 178418361HCID 178418361, compound

Product 1

HCID 2063904Ethyl 3-(3-fluorophenyl)-3-oxopropanoateYield 91%

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent2×

Conditions

Temperature
120 °C

Procedure

Into a three-neck 2 L round-bottom flask equipped with an addition funnel, nitrogen inlet, magnetic stirrer, heating mantle, thermocouple and condenser, was placed 21.7 g (0.543 moles) of a 60%-in-oil dispersion of sodium hydride. To this was added 1 L dry hexane and the resulting suspension was stirred for 15 minutes. Stirring was halted and the solids were allowed to settle and the clear supernatant containing the hexane and dissolved oil was then removed via a cannula. Diethyl carbonate (1 L) was added to the solids and the suspension was heated to 120° C. To the hot suspension was cautiously added dropwise, over 40 minutes, a solution of 100 g (0.494 moles) of m-fluoro acetophenone dissolved in 250 mL of diethyl carbonate. As addition proceeded a reaction initiated, hydrogen was evolved and the color changed to tan. After the acetophenone-derivative addition was complete, the reaction was heated for 1 additional hour. The reaction mixture was cooled and was poured into a 2 L separatory funnel. The diethyl carbonate layer was twice washed with 10% acetic acid solution, dried over MgSO4 and filtered. The product was purified by vacuum distillation (bp 114-117° C. at 0.8-0.9 mm Hg) in 91% yield.

Workup

  1. customInto a three-neck 2 L round-bottom flask equipped with an addition funnel, nitrogen inlet, magnetic stirrer
  2. temperatureheating mantle
  3. customthermocouple and condenser, was placed
  4. stirringStirring
  5. dissolutiondissolved oil
  6. customwas then removed via a cannula
  7. additionDiethyl carbonate (1 L) was added to the solids
  8. additionTo the hot suspension was cautiously added dropwise, over 40 minutes
  9. additionAs addition
  10. temperaturethe reaction was heated for 1 additional hour
  11. temperatureThe reaction mixture was cooled
  12. additionwas poured into a 2 L separatory funnel
  13. washThe diethyl carbonate layer was twice washed with 10% acetic acid solution
  14. dry with materialdried over MgSO4
  15. filtrationfiltered
  16. distillationThe product was purified by vacuum distillation (bp 114-117° C. at 0.8-0.9 mm Hg) in 91% yield

Sources & evidence

ORD record
ord-8cda4be51cab4cafaba37517738d4ddc
Source dataset
uspto-grants-2005_01
Patent number
US06841680B2

Reaction notes

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