Acetaminophen → 5-(4-Acetamidophenoxy)-2-nitropyridine

HRID 1294071Notes

Reaction equation

HRID 1294071 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([N+:8]([O-:10])=[O:9])=[N:6][CH:7]=1.C([O-])([O-])=O.[Cs+].[Cs+].[C:17]([NH:20][C:21]1[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][CH:22]=1)(=[O:19])[CH3:18]>CN(C=O)C>[C:17]([NH:20][C:21]1[CH:26]=[CH:25][C:24]([O:27][C:2]2[CH:3]=[CH:4][C:5]([N+:8]([O-:10])=[O:9])=[N:6][CH:7]=2)=[CH:23][CH:22]=1)(=[O:19])[CH3:18]

Participants

5

Reactant 3

HCID 1983AcetaminophenHCID 10796Cesium carbonateHCID 8176205-Bromo-2-nitropyridine

Product 1

HCID 177555355-(4-Acetamidophenoxy)-2-nitropyridineYield 59.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 5-bromo2-nitropyridine (2.03 g, 10.0 mmol) in DMF (30 mL) was added Cs2CO3 (4.9 g, 15.0 mmol) followed by 4-acetylaminophenol (1.66 g, 11.0 mmol) in DMF (30 mL) at 0° C. then stirred at room temperature overnight. The mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, dried over. Na2SO4 then evaporated. Sequence purification on SiO2 column chromatography and recrystalization from ethyl acetate gave 5-(4-acetamidophenoxy)-2-nitropyridine (1.62 g, 59%). Hydrogenation of 5-(4-acetamidophenoxy)-2-nitropyridine (879.0 mg, 3.22 mmol) with 5% Pd—C in MeOH (80 mL) gave the title compound (575.7 mg, 74%): MS m/e 244 (M+1).

Workup

  1. extractionThe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with water and brine
  3. customdried over
  4. customNa2SO4 then evaporated
  5. customSequence purification
  6. customon SiO2 column chromatography and recrystalization from ethyl acetate

Sources & evidence

ORD record
ord-9e1774640cb74617a9f989f421af6ef3
Source dataset
uspto-grants-2007_07
Patent number
US07238813B2

Reaction notes

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