Acetic Acid → Methyl 2-{(3,4-difluorophenyl)methylene}-3-oxobutyrate

HRID 2085381Notes

Reaction equation

HRID 2085381 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[F:10])[CH:5]=O.[C:11]([O:17][CH3:18])(=[O:16])[CH2:12][C:13]([CH3:15])=[O:14].N1CCCCC1.C(O)(=O)C>C1C=CC=CC=1>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[C:12]([C:13](=[O:14])[CH3:15])[C:11]([O:17][CH3:18])=[O:16])[CH:7]=[CH:8][C:9]=1[F:10]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 7757Methyl acetoacetateHCID 8082PiperidineHCID 5880883,4-Difluorobenzaldehyde

Product 1

HCID 54038767Methyl 2-{(3,4-difluorophenyl)methylene}-3-oxobutyrateYield 41%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

A mixture of 3,4-difluorobenzaldehyde (14.2 g, 0.100 mol), methyl acetoacetate (12.2 g, 0.105 mol), piperidine (0.430 g, 5 mmol), and acetic acid (0.30 g, 5 mmol) in benzene (150 mL) was stirred and heated at reflux temperature (equipped with a Dean-Stark trap) for 8 h. The benzene was evaporated and the residue was dissolved in ethyl acetate (200 mL). The resulting solution was washed with brine (50 mL), saturated potassium bisulfate solution (50 mL), and saturated sodium bicarbonate solution. The ethyl acetate solution was dried over magnesium sulfate and the solvent was removed under reduced pressure. The residue was purified by column chromatography (EtOAc/hexane, 1/9 to 3/20), giving the desired product as a yellow oil (9.80 g, 41%) which was used in the subsequent step without any further characterization.

Workup

  1. temperatureheated
  2. temperatureat reflux temperature (
  3. customequipped with a Dean-Stark trap) for 8 h
  4. customThe benzene was evaporated
  5. dissolutionthe residue was dissolved in ethyl acetate (200 mL)
  6. washThe resulting solution was washed with brine (50 mL), saturated potassium bisulfate solution (50 mL), and saturated sodium bicarbonate solution
  7. dry with materialThe ethyl acetate solution was dried over magnesium sulfate
  8. customthe solvent was removed under reduced pressure
  9. customThe residue was purified by column chromatography (EtOAc/hexane, 1/9 to 3/20)

Sources & evidence

ORD record
ord-2b7488a41a694af5982f18a4d40600a7
Source dataset
uspto-grants-2004_04
Patent number
US06720324B2

Reaction notes

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