反応 #220919

反応方程式

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

溶媒

THF

THF

THF

反応条件

後処理

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
   その他The solvent was evaporated
5. 5
   workup.DISSOLUTIONthe residue was dissolved to the mixture of water (80 ml) and ethyl acetate (80 ml)
6. 6
   その他the phases were separated
7. 7
   洗浄The organic phase was washed with 1 M Na2CO3 (6×30 ml)
8. 8
   乾燥dried over Na2SO4
9. 9
   その他evaporated
10. 10
    その他The oily residue was crystallised from ethyl acetate

実験手順

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).

出典