Ethanol → 3-(2-Trifluoromethylphenyl)pentanedioic acid

HRID 406375Notes

Reaction equation

HRID 406375 reaction equation
N1CCCCC1.[F:7][C:8]([F:18])([F:17])[C:9]1[CH:16]=[CH:15][CH:14]=[CH:13][C:10]=1[CH:11]=O.[C:19]([O:25]CC)(=[O:24])[CH2:20]C(C)=O.[OH-:28].[K+].[CH2:30]([OH:32])[CH3:31]>>[F:7][C:8]([F:18])([F:17])[C:9]1[CH:16]=[CH:15][CH:14]=[CH:13][C:10]=1[CH:11]([CH2:20][C:19]([OH:25])=[O:24])[CH2:31][C:30]([OH:28])=[O:32]

Participants

6

Reactant 5

HCID 702EthanolHCID 8082PiperidineHCID 8868Ethyl AcetoacetateHCID 14797Potassium HydroxideHCID 123067o-(Trifluoromethyl)benzaldehyde

Product 1

HCID 666189203-(2-Trifluoromethylphenyl)pentanedioic acid

Procedure

Piperidine (1.0 mL) was added to 2-trifluoromethylbenzaldehyde (5.0 g) and ethyl acetoacetate (7.27 mL) at 0° C. Then, the mixture was brought to room temperature and stirred for four days. Ethanol (50 mL) was added to the resulting reaction mixture, which was stirred with refluxing for five hours. Concentration under reduced pressure gave an oil. The resulting oil was simply purified by silica gel column chromatography (mobile phase:ethyl acetate/heptane=0 to 40%). Although the oil (7.81 g) contained a large amount of impurities, the oil was dissolved in ethanol (18.5 mL) and water (24.9 mL) to use the oil directly for the next reaction. Potassium hydroxide (32.7 g) was added and the reaction was initiated by heating under reflux. After 1.5 hours, the reaction mixture was partitioned with water and diethyl ether. The resulting aqueous layer was neutralized with concentrated hydrochloric acid (20 mL). Following extraction with methylene chloride twice, drying over magnesium sulfate and concentration under reduced pressure gave a yellow solid. The resulting crude product was recrystallized from ethyl acetate (30 mL) and heptane (65 mL) to obtain the title compound (1.2 g) as a white powder.

Workup

  1. customwas brought to room temperature
  2. stirringwas stirred
  3. temperaturewith refluxing for five hours
  4. concentrationConcentration under reduced pressure
  5. customgave an oil
  6. customThe resulting oil was simply purified by silica gel column chromatography (mobile phase:ethyl acetate/heptane=0 to 40%)
  7. dissolutionthe oil was dissolved in ethanol (18.5 mL)
  8. customdirectly for the next reaction
  9. temperatureby heating
  10. temperatureunder reflux
  11. waitAfter 1.5 hours
  12. customthe reaction mixture was partitioned with water and diethyl ether
  13. extractionextraction with methylene chloride twice
  14. dry with materialdrying over magnesium sulfate and concentration under reduced pressure
  15. customgave a yellow solid
  16. customThe resulting crude product was recrystallized from ethyl acetate (30 mL) and heptane (65 mL)

Sources & evidence

ORD record
ord-e83e3a4979a64da39a77719f96fd5fc7
Source dataset
uspto-grants-2014_06
Patent number
US08754100B2

Reaction notes

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