Acetanilide → 4-(4-Acetamidophenyl)-4-oxobutanoic acid

HRID 1168466Notes

Reaction equation

HRID 1168466 reaction equation
[Cl-].[Al+3].[Cl-].[Cl-].CN(C)C=O.[C:10]([NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)(=[O:12])[CH3:11].[C:20]1(=[O:26])[O:25][C:23](=[O:24])[CH2:22][CH2:21]1>Cl>[C:10]([NH:13][C:14]1[CH:19]=[CH:18][C:17]([C:20](=[O:26])[CH2:21][CH2:22][C:23]([OH:25])=[O:24])=[CH:16][CH:15]=1)(=[O:12])[CH3:11]

Participants

6

Reactant 4

HCID 904AcetanilideHCID 6228DimethylformamideHCID 7922Succinic anhydrideHCID 6451240Aluminum(III) Chloride

Product 1

HCID 2323374-(4-Acetamidophenyl)-4-oxobutanoic acidYield 42.6%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

To a flask charged with anhydrous aluminum chloride (128.1 g, 0.961 mol) was added dropwise neat dimethylformamide (21 mL, 0.27 mol) at a rate such that the internal temperature remained below 70° C. The resulting mixture was thoroughly mixed. To the stirred thick mixture was added in ten portions a mixture of acetanilide (13.53 g, 0.100 mol) and succinic anhydride (10.01 g, 0.100 mol) that had been preground together with a mortar and pestle. The addition rate was controlled to keep the internal temperature at less than or equal to 72° C. The resulting mixture was stirred at 65° C. to 70° C. for 1.25 hours, then poured hot onto ice (1.0 kg). The mixture was acidified with concentrated hydrochloric acid (60 mL), and the resulting solids were filtered. The filtercake was washed with 0.05 M hydrocloric acid and allowed to air dry overnight. The filtercake was suspended in hot water (93 mL), methanol (120 mL) was added, and the hot cloudy solution was gravity filtered. The filtrate was boiled down to 100 mL volume and allowed to cool. The solids were filtered, washed with water-methanol, and dried in vacuo to give 10.03 g of 4-(4-acetylamino-phenyl)-4-oxo-butyric acid as a tan solid.

Workup

  1. customremained below 70° C
  2. additionThe resulting mixture was thoroughly mixed
  3. additionTo the stirred thick mixture was added in ten portions
  4. customat less than or equal to 72° C
  5. additionpoured hot onto ice (1.0 kg)
  6. filtrationthe resulting solids were filtered
  7. washThe filtercake was washed with 0.05 M hydrocloric acid
  8. customto air dry overnight
  9. additionmethanol (120 mL) was added
  10. filtrationfiltered
  11. temperatureto cool
  12. filtrationThe solids were filtered
  13. washwashed with water-methanol
  14. customdried in vacuo

Sources & evidence

ORD record
ord-1b0000e745934269ad14aed1ebcb2796
Source dataset
uspto-grants-2003_09
Patent number
US06624196B2

Reaction notes

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