Dimethylformamide → (αZ)-4-Bromo-α-[(dimethylamino)methylene]benzeneacetaldehyde

HRID 1257802Notes

Reaction equation

HRID 1257802 reaction equation
P(Cl)(Cl)(Cl)=O.[CH3:6][N:7]([CH3:10])[CH:8]=O.[Br:11][C:12]1[CH:17]=[CH:16][C:15]([CH2:18][C:19](O)=[O:20])=[CH:14][CH:13]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(O)C.O>[Br:11][C:12]1[CH:17]=[CH:16][C:15](/[C:18](=[CH:8]/[N:7]([CH3:10])[CH3:6])/[CH:19]=[O:20])=[CH:14][CH:13]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 24813Phosphorus oxychlorideHCID 74654Benzeneacetic acid, 4-bromo-

Product 1

HCID 13079816(αZ)-4-Bromo-α-[(dimethylamino)methylene]benzeneacetaldehyde

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

Phosphoryl chloride (55.0 mL, 590 mmol) was added dropwise to N,N-dimethylformamide (80.0 mL) at 0° C. The reaction mixture was stirred at 0° C. for an additional 30 min after which 4-bromophenylacetic acid (43.0 g, 200 mmol) was added portion wise. The resulting mixture was heated at 70° C. overnight. After cooling, the reaction mixture was added slowly to a mixture of ice and water with external cooling. Ice was added intermittently to keep the temperature<10° C. When the quenching was complete, potassium carbonate and ice were added slowly until pH 11 was achieved. Small quantities of ethanol were added to control frothing. To the alkaline mixture was added toluene (120 mL), and the reaction mixture was refluxed for 1.5 hours and cooled to ambient temperature. The aqueous layer was extracted with toluene (2×50 mL). The combined organic extracts were washed with water, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was recrystallized from dichloromethane/hexanes to give the desired product. (26.5 g, 52%) LCMS: (M+H)=281.0/283.0.

Workup

  1. additionwas added portion wise
  2. temperatureAfter cooling
  3. additionIce was added intermittently
  4. customthe temperature<10° C
  5. temperaturethe reaction mixture was refluxed for 1.5 hours
  6. temperaturecooled to ambient temperature
  7. extractionThe aqueous layer was extracted with toluene (2×50 mL)
  8. washThe combined organic extracts were washed with water
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was recrystallized from dichloromethane/hexanes

Sources & evidence

ORD record
ord-00ce1282729e4262a93af0fe261d98ff
Source dataset
uspto-grants-2013_06
Patent number
US08461330B2

Reaction notes

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