p-Toluenesulfonic acid → 3-(Methylamino)phenol

HRID 2120920Notes

Reaction equation

HRID 2120920 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1.[C:9]1(C)C=CC(S(O)(=O)=O)=CC=1>C(OC=O)C.C1COCC1>[CH3:9][NH:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 6101p-Toluenesulfonic acidHCID 115683-Aminophenol

Product 1

HCID 108205133-(Methylamino)phenolYield 4,810.1%

Reagents, catalysts & solvents 2

HCID 8025Ethyl formateSolventHCID 8028TetrahydrofuranSolvent

Procedure

3-Aminophenol (5.37 g, 49.2 mmol) in ethylformate (30 mL) was treated with p-toluenesulfonic acid (50 mg) and heated at reflux. After 18 hours, the volatiles were evaporated under reduced pressure. The residue was taken up in ethyl acetate and washed with 1N HCl, saturated NaHCO3, brine, dried (Na2SO4), filtered, and the filtrate concentrated under reduced pressure. The residue was dissolved in THF (25 mL) and treated with 1M borane tetrahydofuran complex (27.2 mL, 27.2 mmol) in THF. After 18 hours at ambient temperature, the mixture was carefully quenched by addition of 1N HCl. After stirring for 30 minutes, the solution was basified and extracted with ethyl acetate. The organic layer was separated, washed with brine, dried (Na2SO4), filtered, and the filtrate concentrated under reduced pressure. The residue was purified by flash chromatography (30% ethyl acetate/hexanes) to provide the title compound as a viscous yellow oil (1.72 g, 28% yield). 1H NMR (300 MHz, CDCl3) δ 7.03 (t, 1H), 6.13-6.24 (m, 2H), 6.11 (t, 1H), 4.54 (bs, 1H), 3.72 (bs, 1H), 2.82 (s, 3H); MS (DCI/NH3) 124 (M+H)+, 141 (M+NH4)+.

Workup

  1. temperatureheated
  2. temperatureat reflux
  3. customthe volatiles were evaporated under reduced pressure
  4. washwashed with 1N HCl, saturated NaHCO3, brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationthe filtrate concentrated under reduced pressure
  8. dissolutionThe residue was dissolved in THF (25 mL)
  9. waitAfter 18 hours at ambient temperature
  10. customthe mixture was carefully quenched by addition of 1N HCl
  11. extractionextracted with ethyl acetate
  12. customThe organic layer was separated
  13. washwashed with brine
  14. dry with materialdried (Na2SO4)
  15. filtrationfiltered
  16. concentrationthe filtrate concentrated under reduced pressure
  17. customThe residue was purified by flash chromatography (30% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-9c33bf4bc06a4907ada5483558eb1471
Source dataset
uspto-grants-2004_02
Patent number
US06693136B1

Reaction notes

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