Methanol → Methyl p-aminosalicylate

HRID 1378638Notes

Reaction equation

HRID 1378638 reaction equation
OS(O)(=O)=O.[NH2:6][C:7]1[CH:8]=[C:9]([OH:16])[C:10](=[CH:14][CH:15]=1)[C:11]([OH:13])=[O:12].[CH3:17]O>>[NH2:6][C:7]1[CH:8]=[C:9]([OH:16])[C:10](=[CH:14][CH:15]=1)[C:11]([O:13][CH3:17])=[O:12]

Participants

4

Reactant 3

HCID 887MethanolHCID 1118Sulfuric AcidHCID 46494-Aminosalicylic Acid

Product 1

HCID 77787Methyl p-aminosalicylateYield 88%

Procedure

Absolute methanol (100 mL) and fresh concentrated H2SO4 are carefully combined in a 250 mL round button flask with continuous stirring (exothermic). 4-Aminosalicylic acid (10.0 grams, 65.4 mmol) is added to produce a dark solution, which is heated under reflux for 6 hours. The product is allowed to cool and then concentrated on a rotary evaporator to approximately half the original volume. At this point a solid precipitate appears. The concentrate is poured into 400 mL of water, and the resulting suspension titrated to approximately pH 3, by stepwise addition of 5N NaOH (to pH 6.5), followed by solid Na2CO3, with evolution of CO2 gas. The concentrate was chilled on ice, and the resulting precipitate collected by filtration. The filtrate is washed with cold water, and then dried in vacuo over NaOH pellets, to afford 9.6 grams (88% yield) of methyl 4-aminosalicylate, a pale lavendar powder (m.p. 115°-117° C.). The structure was confirmed by 1H NMR spectrometry in d6-acetone.

Workup

  1. customto produce a dark solution, which
  2. temperatureis heated
  3. temperatureunder reflux for 6 hours
  4. temperatureto cool
  5. concentrationconcentrated on a rotary evaporator to approximately half the original volume
  6. additionThe concentrate is poured into 400 mL of water
  7. additionthe resulting suspension titrated to approximately pH 3, by stepwise addition of 5N NaOH (to pH 6.5)
  8. temperatureThe concentrate was chilled on ice
  9. filtrationthe resulting precipitate collected by filtration
  10. washThe filtrate is washed with cold water
  11. dry with materialdried in vacuo over NaOH pellets

Sources & evidence

ORD record
ord-55dade4ea467432c962be973e418b89f
Source dataset
uspto-grants-1997_09
Patent number
US05668257

Reaction notes

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