Ammonium Hydroxide → Isoquinolin-6-ol

HRID 2220328Notes

Reaction equation

HRID 2220328 reaction equation
C[O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[N:8][CH:7]=[CH:6]2.Cl.N1C=CC=CC=1.[OH-].[NH4+]>O>[CH:9]1[C:10]2[C:5](=[CH:4][C:3]([OH:2])=[CH:12][CH:11]=2)[CH:6]=[CH:7][N:8]=1

Participants

5

Reactant 3

HCID 14923Ammonium HydroxideHCID 10176127Pyridinium chlorideHCID 110409786-Methoxyisoquinoline

Product 1

HCID 135483582Isoquinolin-6-olYield 27.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Heat a mixture of 6-methoxy-isoquinoline (2.1 g, 13.2 mmol) and pyridine hydrochloride (30 g) in a heavy walled screw cap sealed tube at 160° C. overnight. Cool to room temperature, add water and concentrated ammonium hydroxide to bring the pH of the mixture to 10-11, extract with ethyl acetate (4 times), wash the combined organic extracts with water (4 times), and concentrate under reduced pressure. Purification by medium pressure liquid chromatography eluting with 0-3% of 2N NH3/MeOH in dichloromethane afford the title compound (520 mg, 27%): δH (DMSO-d6, 400 MHz): 7.09 (s, 1H), 7.19 (dd, 1H, J=9, 2Hz),7.56(d, 1H, J=6 Hz),7.94 (d, 1H, J=9 Hz), 8.29 (d, 1H, J=6 Hz), 9.05 (s, 1H), 10.36 (s, 1H).

Workup

  1. temperatureHeat
  2. customcap
  3. customsealed tube at 160° C. overnight
  4. extractionextract with ethyl acetate (4 times)
  5. washwash the combined organic extracts with water (4 times)
  6. concentrationconcentrate under reduced pressure
  7. customPurification by medium pressure liquid chromatography
  8. washeluting with 0-3% of 2N NH3/MeOH in dichloromethane

Sources & evidence

ORD record
ord-7b506bf488144e3c87c4171e1fcedf79
Source dataset
uspto-grants-2008_08
Patent number
US07417064B2

Reaction notes

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