Acetaminophen → 6-(4-Acetylaminophenoxy)-hexanoic acid methyl ester

HRID 2169705Notes

Reaction equation

HRID 2169705 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+].Br[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][C:26]([O:28][CH3:29])=[O:27]>CC(C)=O>[CH3:29][O:28][C:26](=[O:27])[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][O:9][C:8]1[CH:10]=[CH:11][C:5]([NH:1][C:2](=[O:3])[CH3:4])=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 1983AcetaminophenHCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 4170292Methyl 6-Bromohexanoate

Product 1

HCID 497644916-(4-Acetylaminophenoxy)-hexanoic acid methyl esterYield 66%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a mixture of Paracetamol (250 g, 1.654 mol), anhydrous K2CO3 (800 g, 5.789 mol) and sodium iodide (17 g, 113 mmol) in anhydrous acetone (5 liters) was added methyl 6-bromohexanoate (470 g, 2.25 mol) and refluxed for 60 hours. Acetone was distilled off and water (3 liter) was added. Crude 19 was filtered, dried and recrystallised from a mixture of chloroform:hexane (1:5) to give pure 19 (195 g, 66%) as a white powder. The melting point was found to be 96.4-98.8° C. The product was tested by HPLC and found to be 99%+ pure. The structure was confirmed with NMR.

Workup

  1. temperaturerefluxed for 60 hours
  2. distillationAcetone was distilled off
  3. additionwater (3 liter) was added
  4. filtrationCrude 19 was filtered
  5. customdried
  6. customrecrystallised from a mixture of chloroform:hexane (1:5)

Sources & evidence

ORD record
ord-dc3b571ec98a47559c87917ffffa2912
Source dataset
uspto-grants-2015_06
Patent number
USRE045548E1

Reaction notes

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