Reaction #220913

Reaction equation

4-acetamidophenol

sodium hydride

2-methyl-oxirane-2-carboxylic acid (3-methyl-4-nitrophenyl)amide

→

3-(4-Acetylaminophenoxy)-2-hydroxy-2-methyl-N-(3-methyl-4-nitrophenyl)propionamide

Solvents

THF

THF

THF

Conditions

Workup

1. 1
   workup.ADDITIONthe temperature was kept below 5° C. during the addition
2. 2
   workup.STIRRINGstirred at this temperature for 7 h
3. 3
   Temperatureto cool to the room temperature
4. 4
   OtherThe solvent was evaporated
5. 5
   workup.DISSOLUTIONthe residue was dissolved to the mixture of water (150 ml) and ethyl acetate (150 ml)
6. 6
   Otherthe phases were separated
7. 7
   ExtractionThe aqueous phase was extracted with ethyl acetate (4×150 ml)
8. 8
   WashThe combined organic phase was washed with 1 M Na2CO3 (5×100 ml)
9. 9
   Dryingdried over Na2SO4
10. 10
    Otherevaporated
11. 11
    OtherThe oily residue was crystallised from the mixture of ethyl acetate-diethyl ether (10:1)
12. 12
    OtherThe crude product was recrystallised from ethyl acetate

Procedure

A solution of 4-acetamidophenol (2.9 g, 19 mmol) in THF (60 ml) was added dropwise to a stirred suspension of sodium hydride (0.46 g, 19 mmol, 60% dispersion in mineral oil) in THF (60 ml) and the temperature was kept below 5° C. during the addition. The mixture was stirred for 10 min and a solution of 2-methyl-oxirane-2-carboxylic acid (3-methyl-4-nitrophenyl)amide (3.05 g, 13 mmol) in THF (120 ml) was added. The mixture was heated to 60° C. and stirred at this temperature for 7 h, and allowed to cool to the room temperature. The solvent was evaporated and the residue was dissolved to the mixture of water (150 ml) and ethyl acetate (150 ml). The pH was adjusted to 2-3 with 2 M HCl and the phases were separated. The aqueous phase was extracted with ethyl acetate (4×150 ml). The combined organic phase was washed with 1 M Na2CO3 (5×100 ml), dried over Na2SO4 and evaporated. The oily residue was crystallised from the mixture of ethyl acetate-diethyl ether (10:1). The crude product was recrystallised from ethyl acetate. The yield was 2.5 g. 1H NMR (DMSO-d6): 1.42 (3H, s), 1.99 (3H, s), 2.53 (3H, s), 3.93 (1H, d, J=9.6 Hz), 4.16 (1H, d, J=9.6 Hz), 6.20 (1H, bs), 6.84 (2H, d, J=9.0 Hz), 7.44 (2H, d, J=9.0 Hz), 7.88 (1H, dd, J=9.0 Hz and 2.3 Hz), 7.93 (1H, d, J=2.3 Hz), 8.04 (1H, d, J=9.0 Hz), 9.76 (1H, s), 10.15 (1H, bs).

Source