4-Methylbenzaldehyde → Methyl 2-(4-methylbenzylidene)-3-oxobutanoate

HRID 1912526Notes

Reaction equation

HRID 1912526 reaction equation
[CH3:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][CH:3]=1.[C:10]([O:16][CH3:17])(=[O:15])[CH2:11][C:12]([CH3:14])=[O:13]>C1C=CC=CC=1.N1CCCCC1.C(O)(=O)C>[CH3:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[C:11]([C:12](=[O:13])[CH3:14])[C:10]([O:16][CH3:17])=[O:15])=[CH:4][CH:3]=1

Participants

6

Reactant 2

HCID 77254-MethylbenzaldehydeHCID 7757Methyl acetoacetate

Product 1

HCID 54176673Methyl 2-(4-methylbenzylidene)-3-oxobutanoateYield 84.7%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 8082PiperidineCatalystHCID 241BenzeneSolvent

Procedure

A solution of 4-methylbenzaldehyde (0.981 ml, 8.32 mmol), methyl acetoacetate (0.898 ml, 8.32 mmol), piperidine (0.041 ml, 0.416 mmol), and acetic acid (0.024 ml, 0.416 mmol) in benzene (12.5 ml) was refluxed with a Dean Stark apparatus for 1 day. The reaction was concentrated; the residue was dissolved in EtOAc, washed with water, sat. NaHCO3, Brine, dried with Na2SO4, filtered, and concentrated. Purification with column chromatography afforded a 2:3 mixture of E/Z isomers of methyl 2-(4-methylbenzylidene)-3-oxobutanoate (1539.1 mg, 7.05 mmol, 84.7% yield) as yellow oil: E=1H NMR (400 MHz, CHLOROFORM-d) d=7.67 (s, 1 H), 7.29 (d, J=8.2 Hz, 2 H), 7.18 (d, J=8.1 Hz, 2 H), 3.83 (s, 3 H), 2.37 (s, 3 H), 2.36 (s, 3 H) LCMS (m/z) ES+=219 (M+1). Z=1H NMR (400 MHz, CHLOROFORM-d) d=7.55 (s, 1 H), 7.33 (d, J=8.2 Hz, 2 H), 7.20 (d, J=8.1 Hz, 2 H), 3.86 (s, 3 H), 2.42 (s, 3 H), 2.38 (s, 3 H); LCMS (m/z) ES+=219 (M+1).

Workup

  1. concentrationThe reaction was concentrated
  2. dissolutionthe residue was dissolved in EtOAc
  3. washwashed with water, sat. NaHCO3, Brine
  4. dry with materialdried with Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification with column chromatography
  8. customafforded

Sources & evidence

ORD record
ord-d5c2b909ef1d43348ec4d464bfdecf03
Source dataset
uspto-grants-2013_12
Patent number
US08609653B2

Reaction notes

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