Acetaminophen → 3-Pyridinecarboxylic acid, 4-(acetylamino)phenyl ester

HRID 2200842Notes

Reaction equation

HRID 2200842 reaction equation
[NH:1]([C:5]1[CH:11]=[CH:10][C:8]([OH:9])=[CH:7][CH:6]=1)[C:2]([CH3:4])=[O:3].Cl.[C:13](Cl)(=[O:20])[C:14]1[CH:19]=[CH:18][CH:17]=[N:16][CH:15]=1>C1COCC1>[C:13]([O:9][C:8]1[CH:10]=[CH:11][C:5]([NH:1][C:2](=[O:3])[CH3:4])=[CH:6][CH:7]=1)(=[O:20])[C:14]1[CH:19]=[CH:18][CH:17]=[N:16][CH:15]=1

Participants

4

Reactant 2

HCID 1983AcetaminophenHCID 884383-Pyridinecarbonyl chloride, hydrochloride (1:1)

Product 1

HCID 32379893-Pyridinecarboxylic acid, 4-(acetylamino)phenyl esterYield 78%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

TEA (1.2 ml, 8.6 mmol, 5.0 eq) was added to a solution of paracetamol [4147] (0.26 g, 1.7 mmol, 1.0 eq) in dry THF under argon atmosphere. At 0° C., nicotinoyl chloride hydrochloride [296] (1.53 gm, 8.6 mmol, 5.0 eq) was added to the above reaction mixture. The reaction mixture was stirred at room temperature for 24 h. After 24 h, organic solvent was evaporated under vacuum and residue was dissolved in dichloromethane (50 ml) and washed with a 10% solution of NaHCO3 (15 ml) and then with brine (10 ml) followed by drying of organic layer over anhydrous sodium sulfate. Evaporation of the solvents provided white solid which was purified by silica gel column chromatography (4% MeOH: DCM, 100-200 mesh silica) to give the product 4-acetamidophenyl nicotinate [297] (0.34 g, 78%).

Workup

  1. waitAfter 24 h
  2. customorganic solvent was evaporated under vacuum and residue
  3. dissolutionwas dissolved in dichloromethane (50 ml)
  4. washwashed with a 10% solution of NaHCO3 (15 ml)
  5. dry with materialby drying of organic layer over anhydrous sodium sulfate
  6. customEvaporation of the solvents
  7. customprovided white solid which
  8. customwas purified by silica gel column chromatography (4% MeOH: DCM, 100-200 mesh silica)

Sources & evidence

ORD record
ord-aad552fbab964712a27d5767d392364c
Source dataset
uspto-grants-2016_06
Patent number
US09359376B2

Reaction notes

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