Acetaminophen → 2-(4-Acetylamino-phenoxy)-propionic acid methyl ester

HRID 1957824Notes

Reaction equation

HRID 1957824 reaction equation
[NH:1]([C:5]1[CH:11]=[CH:10][C:8]([OH:9])=[CH:7][CH:6]=1)[C:2]([CH3:4])=[O:3].C([O-])([O-])=O.[K+].[K+].[I-].[Na+].Cl[CH:21]([CH3:26])[C:22]([O:24][CH3:25])=[O:23]>CC(C)=O>[CH3:25][O:24][C:22](=[O:23])[CH:21]([O:9][C:8]1[CH:10]=[CH:11][C:5]([NH:1][C:2](=[O:3])[CH3:4])=[CH:6][CH:7]=1)[CH3:26]

Participants

6

Reactant 4

HCID 1983AcetaminophenHCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 28659Methyl 2-chloropropionate

Product 1

HCID 549413982-(4-Acetylamino-phenoxy)-propionic acid methyl esterYield 27,257.9%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a mixture of Paracetamol (150 grams, 992 mmol), anhydrous K2CO3 (540 Kg, 3.91 mol) and sodium iodide (18 g, 120 mmol) in anhydrous acetone (3 liters) was added methyl 2-chloropropionate (180 g, 1.469 mmol) and refluxed for 80 hours. Acetone was distilled off and water (3 liter) was added. Crude 16 was extracted into chloroform, dried over Na2SO4, distilled in hexane (750 ml), filtered and recrystallised in methanol to give pure 16 (95 g, 40.4%) as a white powder. The melting point was found to be 96.5-98.2° C. The product was tested by HPLC and found to be 99%+ pure. The structure was confirmed with NMR.

Workup

  1. temperaturerefluxed for 80 hours
  2. distillationAcetone was distilled off
  3. additionwater (3 liter) was added
  4. extractionCrude 16 was extracted into chloroform
  5. dry with materialdried over Na2SO4
  6. distillationdistilled in hexane (750 ml)
  7. filtrationfiltered
  8. customrecrystallised in methanol

Sources & evidence

ORD record
ord-3e1294db43c247a69c9cd761403e117c
Source dataset
uspto-grants-2013_04
Patent number
US08409559B2

Reaction notes

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