Réaction #220919

Équation de réaction

4-acetamidophenol

sodium hydride

(2R)-3-bromo-2-hydroxy-2-methyl-N-(3-methyl-4-nitrophenyl)propionamide

→

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

Solvants

THF

THF

THF

Conditions de réaction

Traitement

1. 1
   workup.ADDITIONthe temperature was kept below 5° C. during the addition
2. 2
   workup.STIRRINGThe mixture was stirred at room temperature for 30 min
3. 3
   workup.WAITat 60° C. for 5 h
4. 4
   AutreThe solvent was evaporated
5. 5
   workup.DISSOLUTIONthe residue was dissolved to the mixture of water (80 ml) and ethyl acetate (80 ml)
6. 6
   Autrethe phases were separated
7. 7
   LavageThe organic phase was washed with 1 M Na2CO3 (6×30 ml)
8. 8
   Séchagedried over Na2SO4
9. 9
   Autreevaporated
10. 10
    AutreThe oily residue was crystallised from ethyl acetate

Mode opératoire

A solution of 4-acetamidophenol 0.62 g, 4.1 mmol) in THF (7 ml) was added dropwise to a stirred suspension of sodium hydride (0.27 g, 6.8 mmol, 60% dispersion in mineral oil) in THF (6 ml) and the temperature was kept below 5° C. during the addition. The mixture was stirred for 10 min and a solution of (2R)-3-bromo-2-hydroxy-2-methyl-N-(3-methyl-4-nitrophenyl)propionamide (0.86 g, 2.7 mmol) in THF (7 ml) was added. The mixture was stirred at room temperature for 30 min and then at 60° C. for 5 h, and allowed to cool to the room temperature. The solvent was evaporated and the residue was dissolved to the mixture of water (80 ml) and ethyl acetate (80 ml). The pH was adjusted to 2-3 with 2 M HCl and the phases were separated. The organic phase was washed with 1 M Na2CO3 (6×30 ml), dried over Na2SO4 and evaporated. The oily residue was crystallised from ethyl acetate. The yield was 0.27 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