Methyl 5-Amino-2-methylbenzoate → Methyl 5-hydroxy-2-methylbenzoate

HRID 577592Notes

Reaction equation

HRID 577592 reaction equation
N[C:2]1[CH:3]=[CH:4][C:5]([CH3:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].N([O-])=[O:14].[Na+]>OS(O)(=O)=O.O.[O-]S([O-])(=O)=O.[Cu+2]>[OH:14][C:2]1[CH:3]=[CH:4][C:5]([CH3:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8]

Participants

6

Reactant 2

HCID 15049977Methyl 5-Amino-2-methylbenzoateHCID 23668193Sodium Nitrite

Product 1

HCID 13929055Methyl 5-hydroxy-2-methylbenzoateYield 67%

Reagents, catalysts & solvents 3

HCID 24462Copper SulfateCatalystHCID 962WaterSolventHCID 1118Sulfuric AcidSolvent

Conditions

Temperature
0 °C

Procedure

To a 0° C. solution of methyl 5-amino-2-methylbenzoate (6.25 g, 37.8 mmol) in H2SO4 (10 mL) and H2O (160 mL) was added NaNO2 (aq., 3.78 N, 10 mL). The resulting mixture was stirred at 0° C. for 10 minutes. After 10 minutes, the mixture was added to a refluxing solution of CuSO4 (1 N, 100 mL) and refluxed for 1 hour. The mixture was cooled to room temperature and extracted with CH2Cl2 (2×200 mL). The organic layers were washed with H2O (50 mL) and brine (50 mL), dried over Na2SO4 and concentrated under vacuum. The residue was purified by column chromatography (petroleum ether/EtOAc=5:1) to give methyl 5-hydroxy-2-methylbenzoate (134a, 4.2 g, 67%) as a yellow solid.

Workup

  1. waitAfter 10 minutes
  2. temperaturerefluxed for 1 hour
  3. temperatureThe mixture was cooled to room temperature
  4. extractionextracted with CH2Cl2 (2×200 mL)
  5. washThe organic layers were washed with H2O (50 mL) and brine (50 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under vacuum
  8. customThe residue was purified by column chromatography (petroleum ether/EtOAc=5:1)

Sources & evidence

ORD record
ord-78f0e1633b3d417cb2ad81625d9c1ca5
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

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