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

HRID 133731

反応式

HRID 133731 の反応式
[C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][CH:6]=1)(=[O:3])[CH3:2].[H-].[Na+].[CH3:14][C:15]1[CH:16]=[C:17]([NH:24][C:25]([C:27]2([CH3:30])[CH2:29][O:28]2)=[O:26])[CH:18]=[CH:19][C:20]=1[N+:21]([O-:23])=[O:22]>C1COCC1>[C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([O:11][CH2:30][C:27]([OH:28])([CH3:29])[C:25]([NH:24][C:17]2[CH:18]=[CH:19][C:20]([N+:21]([O-:23])=[O:22])=[C:15]([CH3:14])[CH:16]=2)=[O:26])=[CH:7][CH:6]=1)(=[O:3])[CH3:2]

参加物

5

反応物 3

HCID 1983AcetaminophenHCID 24758Sodium hydrideHCID 714200032-Methyl-N-(3-methyl-4-nitrophenyl)oxirane-2-carboxamide

生成物 1

HCID 205907153-(4-Acetylaminophenoxy)-2-hydroxy-2-methyl-N-(3-methyl-4-nitrophenyl)propionamide

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒3 回

反応条件

温度
60 °C

実験手順

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).

後処理

  1. additionthe temperature was kept below 5° C. during the addition
  2. stirringstirred at this temperature for 7 h
  3. temperatureto cool to the room temperature
  4. customThe solvent was evaporated
  5. dissolutionthe residue was dissolved to the mixture of water (150 ml) and ethyl acetate (150 ml)
  6. customthe phases were separated
  7. extractionThe aqueous phase was extracted with ethyl acetate (4×150 ml)
  8. washThe combined organic phase was washed with 1 M Na2CO3 (5×100 ml)
  9. dry with materialdried over Na2SO4
  10. customevaporated
  11. customThe oily residue was crystallised from the mixture of ethyl acetate-diethyl ether (10:1)
  12. customThe crude product was recrystallised from ethyl acetate

出典と根拠

ORDレコード
ord-07d9071cc53d4ab9ace08af259831009
出典データセット
uspto-grants-2008_06
特許番号
US07390923B2

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