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

HRID 1840321Notes

Reaction equation

HRID 1840321 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-oxobutyrate

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

A mixture of 3,4-difluorobenzaldehyde (14.2 g, 0.1 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 refluxed with a Dean-Stark trap for 8 hours. Benzene was evaporated, the residue was dissolved in ethyl acetate (200 mL) and washed with brine (50 mL), saturated potassium bisulfate solution (50 mL), and saturated sodium bicarbonate solution in sequence. The ethyl acetate solution was dried (magnesium sulfate), solvent removed under reduced pressure and the residue was purified by column chromatography (SiO2, EtOAc/hexane, 10%-15%). The product, methyl 2-{(3,4-difluorophenyl)methylene}-3-oxobutyrate, was obtained as a yellow oil (0.98 g, 98.3%) and was used in the next step without any further characterization.

Workup

  1. temperaturerefluxed with a Dean-Stark trap for 8 hours
  2. customBenzene was evaporated
  3. dissolutionthe residue was dissolved in ethyl acetate (200 mL)
  4. washwashed with brine (50 mL), saturated potassium bisulfate solution (50 mL), and saturated sodium bicarbonate solution in sequence
  5. dry with materialThe ethyl acetate solution was dried (magnesium sulfate), solvent
  6. customremoved under reduced pressure
  7. customthe residue was purified by column chromatography (SiO2, EtOAc/hexane, 10%-15%)

Sources & evidence

ORD record
ord-80a5d937c0024fe68d384d1a0d579691
Source dataset
uspto-grants-2004_01
Patent number
US06680323B2

Reaction notes

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