Pyridine → Methyl 4-acetylamino-3-(2-hydroxyethoxy)benzoate

HRID 1451082Notes

Reaction equation

HRID 1451082 reaction equation
[NH2:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[O:12][CH2:13][CH2:14][OH:15].[C:16](OC(=O)C)(=[O:18])[CH3:17].N1C=CC=CC=1.C(OCC)(=O)C>ClCCl.O>[C:16]([NH:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[O:12][CH2:13][CH2:14][OH:15])(=[O:18])[CH3:17]

Participants

7

Reactant 4

HCID 1049PyridineHCID 7918Acetic AnhydrideHCID 8857Ethyl AcetateHCID 10560441Methyl 4-amino-3-(2-hydroxyethoxy)benzoate

Product 1

HCID 10491072Methyl 4-acetylamino-3-(2-hydroxyethoxy)benzoateYield 53%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To methyl 4-amino-3-(2-hydroxyethoxy)benzoate (2.98 g, 0.0141 mol) dissolved in dichloromethane (200 mL) was added acetic anhydride (1.49 mL, 0.0156 mol) and pyridine (1.34 mL, 0.0156 mol). After stirring for 3 h at room temperature, thin-layer chromatographic analysis (SiO2, ethyl acetate) showed disappearance of the starting material along with the appearance of a new lower-running spot (Rf =03) indicating the reaction was complete. The reaction was poured into water (70 mL) and the organic layer washed three times with water (50 mL). The organic layer was concentrated and then dried in vacuo. Thin-layer chromatographic analysis (SiO2, ethyl acetate) showed formation of some material as a higher-running spot (Rf =0.8) in addition to the product. Methanol (50 mL) and a catalytic amount of sodium methoxide was added to the residue. After 1 h, thin-layer chromatographic analysis (SiO2, ethyl acetate) showed only the desired product. The solution was neutralized with H+ resin, filtered, and then concentrated. The residue was recrystallized from ethyl acetate to give 1.88 g (53%) of methyl 4-acetylamino-3-(2-hydroxyethoxy)benzoate as an off-white solid.

Workup

  1. washthe organic layer washed three times with water (50 mL)
  2. concentrationThe organic layer was concentrated
  3. customdried in vacuo
  4. additionin addition to the product
  5. additionMethanol (50 mL) and a catalytic amount of sodium methoxide was added to the residue
  6. waitAfter 1 h
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-04d8c2e88b7741e5b425dd1b33827c9e
Source dataset
uspto-grants-1997_02
Patent number
US05602277

Reaction notes

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