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

HRID 133737Notes

Reaction equation

HRID 133737 reaction equation
[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+].Br[CH2:15][C@@:16]([OH:31])([CH3:30])[C:17]([NH:19][C:20]1[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[C:22]([CH3:29])[CH:21]=1)=[O:18]>C1COCC1>[C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([O:11][CH2:30][C@@:16]([OH:31])([CH3:15])[C:17]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[C:22]([CH3:29])[CH:21]=2)=[O:18])=[CH:7][CH:6]=1)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 1983AcetaminophenHCID 24758Sodium hydrideHCID 59903827(2R)-3-bromo-2-hydroxy-2-methyl-N-(3-methyl-4-nitrophenyl)propionamide

Product 1

HCID 11200043(2S)-3-(4-Acetylaminophenoxy)-2-hydroxy-2-methyl-N-(3-methyl-4-nitrophenyl)propionamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

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).

Workup

  1. additionthe temperature was kept below 5° C. during the addition
  2. stirringThe mixture was stirred at room temperature for 30 min
  3. waitat 60° C. for 5 h
  4. customThe solvent was evaporated
  5. dissolutionthe residue was dissolved to the mixture of water (80 ml) and ethyl acetate (80 ml)
  6. customthe phases were separated
  7. washThe organic phase was washed with 1 M Na2CO3 (6×30 ml)
  8. dry with materialdried over Na2SO4
  9. customevaporated
  10. customThe oily residue was crystallised from ethyl acetate

Sources & evidence

ORD record
ord-4b5e172a3afd421b8f0d51bff3dcde79
Source dataset
uspto-grants-2008_06
Patent number
US07390923B2

Reaction notes

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