Reaction #2045006

Reaction equation

methyl 2-chloropropionate

Paracetamol

K2CO3

sodium iodide

→

16

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

Solvents

acetone

Conditions

Workup

1. 1
   Temperaturerefluxed for 80 hours
2. 2
   workup.DISTILLATIONAcetone was distilled off
3. 3
   workup.ADDITIONwater (3 liter) was added
4. 4
   ExtractionCrude 16 was extracted into chloroform
5. 5
   Dryingdried over Na2SO4
6. 6
   workup.DISTILLATIONdistilled in hexane (750 ml)
7. 7
   Filtrationfiltered
8. 8
   Otherrecrystallised in methanol

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.

Source