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

HRID 1586126Notes

Reaction equation

HRID 1586126 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-220b25cbb45f4e77a5f4295ae6eb87dd
Source dataset
uspto-grants-1999_08
Patent number
US05942517

Reaction notes

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