Acetaminophen → N-[4-(3-chloropropoxy)phenyl]acetamide

HRID 330413Notes

Reaction equation

HRID 330413 reaction equation
[C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][CH:6]=1)(=[O:3])[CH3:2].Br[CH:13]([Cl:16])[CH2:14][CH3:15].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O.C(Cl)(Cl)Cl>[Cl:16][CH2:13][CH2:14][CH2:15][O:11][C:8]1[CH:9]=[CH:10][C:5]([NH:4][C:1](=[O:3])[CH3:2])=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 1983AcetaminophenHCID 11430Potassium CarbonateHCID 36872Propane, bromochloro-

Product 1

HCID 5147668N-[4-(3-chloropropoxy)phenyl]acetamideYield 23%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolvent3×HCID 6212ChloroformSolvent

Procedure

A mixture of 4-acetamidophenol (182.2 g, 1.2 moles), bromochloropropane (157.4 g, 1.0 mole), and potassium carbonate (145.0 g, 1.05 moles) was refluxed overnight in 700 ml of acetone. The acetone solution formed white crystals after being placed in a refrigerator overnight. The solution was filtered and the crystals washed with acetone. The filtrate was stripped to dryness, and the residue dissolved in chloroform and extracted with a 5% sodium hydroxide solution. Removal of the chloroform gave an oil. The white crystals obtained earlier were also dissolved in chloroform and extracted with a 5% sodium hydroxide solution. Removal of the chloroform gave a white solid. The white solid and oil were combined with acetone and placed in a refrigerator; white crystals were obtained. A 5-g sample of the white solid was recrystallized from acetone a second time to furnish 1.76 g (after drying in vacuo overnight at 80° C.) (23% yield) of white crystalline product, m.p. 125°-127° C.

Workup

  1. customafter being placed in a refrigerator overnight
  2. filtrationThe solution was filtered
  3. washthe crystals washed with acetone
  4. dissolutionthe residue dissolved in chloroform
  5. extractionextracted with a 5% sodium hydroxide solution
  6. customRemoval of the chloroform
  7. customgave an oil
  8. customThe white crystals obtained earlier
  9. extractionextracted with a 5% sodium hydroxide solution
  10. customRemoval of the chloroform
  11. customgave a white solid
  12. customwhite crystals were obtained
  13. customA 5-g sample of the white solid was recrystallized from acetone a second time
  14. customto furnish

Sources & evidence

ORD record
ord-e28136732474491c86e998fd96289a8f
Source dataset
uspto-grants-1990_01
Patent number
US04895840

Reaction notes

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