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

HRID 2414761Notes

Reaction equation

HRID 2414761 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

A 60%-in-oil dispersion of sodium hydride, 21.7 g (0.543 moles), was placed in a three-neck 2 L round-bottom flask equipped with an addition funnel, nitrogen inlet, magnetic stirrer, heating mantle, thermocouple and condenser with dry hexane (1 L). The resulting suspension was stirred for 15 minutes, stirring was halted and the solids were allowed to settle. The clear supernatant containing the hexane and dissolved oil was then removed via a cannula. Diethyl carbonate (1 L) was added and the suspension was heated to 120° C. To this 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 and then purified by vacuum distillation (bp 114-117° C. at 0.8-0.9 mm Hg) in 91% yield.

Workup

  1. customequipped with an addition funnel, nitrogen inlet, magnetic stirrer
  2. temperatureheating mantle
  3. stirringstirring
  4. dissolutiondissolved oil
  5. customwas then removed via a cannula
  6. additionDiethyl carbonate (1 L) was added
  7. additionTo this suspension was cautiously added dropwise, over 40 minutes
  8. additionAs addition
  9. temperaturethe reaction was heated for 1 additional hour
  10. temperatureThe reaction mixture was cooled
  11. additionwas poured into a 2 L separatory funnel
  12. washThe diethyl carbonate layer was twice washed with 10% acetic acid solution
  13. distillationpurified by vacuum distillation (bp 114-117° C. at 0.8-0.9 mm Hg) in 91% yield

Sources & evidence

ORD record
ord-60defdeef2e24cb5a57c9ac2a586c472
Source dataset
uspto-grants-2004_11
Patent number
US06815447B2

Reaction notes

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