Toluene → 4-methyl-3-oxo-N-phenylpentanamide

HRID 610638Notes

Reaction equation

HRID 610638 reaction equation
C1(C)C=CC=CC=1.[CH3:8][CH:9]([CH3:17])[C:10](=[O:16])[CH2:11][C:12]([O:14]C)=O.C(N)CN.[NH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>O>[CH3:17][CH:9]([CH3:8])[C:10](=[O:16])[CH2:11][C:12]([NH:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:14]

Participants

6

Reactant 4

HCID 1140TolueneHCID 3301EthylenediamineHCID 6115AnilineHCID 2759969Methyl 4-methyl-3-oxopentanoate

Product 1

HCID 102198994-methyl-3-oxo-N-phenylpentanamideYield 157.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A three-necked, 12 L round bottom flask equipped with a mechanical stirrer, a thermometer, and set up for distillation was charged with 2.6 L of toluene, 1.73 kg (12 mol) of methyl 4-methyl-3-oxopentanoate and 72 g (1.18 mol) of ethylenediamine. The mixture was heated to 80° C. and charged with 0.49 kg of aniline. The mixture was brought to reflux and distillation was started. After 40 minutes, a further 0.245 kg of aniline was charged and, at 40 minute intervals, a further two portions of aniline (0.245 and 0.25 kg) were charged. Distillation was continued for a further 1 to 5 hours until a total of 985 mL of solvent was removed. The solution was stirred at room temperature for 16 hours, and a further 550 mL of solvent was removed by vacuum distillation (at approximately 85 mm Hg). The mixture was cooled, and 2 L of water was charged to provide an oil. The mixture was warmed to 40° C., and a further 1.0 L of water was charged. Seven hundred milliliters of toluene/water mixture was removed by vacuum distillation (approximately 20 mm Hg). Two liters of water were charged, and the mixture allowed to stand for 10 days. The product was isolated by filtration and washed with three portions of hexane. Drying in vacuo gave 1.7 kg of 4-methyl-3-oxo-N-phenylpentanamide as a hydrate; mp 46.5-58.8° C.

Workup

  1. customA three-necked, 12 L round bottom flask equipped with a mechanical stirrer
  2. distillationa thermometer, and set up for distillation
  3. temperatureto reflux
  4. distillationdistillation
  5. additiona further 0.245 kg of aniline was charged and, at 40 minute intervals
  6. additiona further two portions of aniline (0.245 and 0.25 kg) were charged
  7. distillationDistillation
  8. waitwas continued for a further 1 to 5 hours until a total of 985 mL of solvent
  9. customwas removed
  10. customa further 550 mL of solvent was removed by vacuum distillation (at approximately 85 mm Hg)
  11. temperatureThe mixture was cooled
  12. addition2 L of water was charged
  13. customto provide an oil
  14. temperatureThe mixture was warmed to 40° C.
  15. customSeven hundred milliliters of toluene/water mixture was removed by vacuum distillation (approximately 20 mm Hg)
  16. additionTwo liters of water were charged
  17. waitto stand for 10 days
  18. customThe product was isolated by filtration
  19. washwashed with three portions of hexane
  20. customDrying in vacuo

Sources & evidence

ORD record
ord-b112982978c344f7b5b7656ee77e3e7e
Source dataset
uspto-grants-1999_12
Patent number
US05998633

Reaction notes

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