Ammonium Hydroxide → Isoquinolin-6-ol

HRID 2218088Notes

Reaction equation

HRID 2218088 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, 2 Hz), 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-a5e30411661744dd9ceeffb9dfab735a
Source dataset
uspto-grants-2008_08
Patent number
US07410982B2

Reaction notes

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