Sodium Hydroxide → 2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-7-hydroxy-3,4-dihydroisoquinolin-1(2H)-one

HRID 577477Notes

Reaction equation

HRID 577477 reaction equation
C(N(CC)C(=O)[O:5][C:6]1[C:15]([Cl:16])=[C:14]2[C:9]([CH2:10][CH2:11][N:12]([CH2:18][C:19]3[C:20]([O:27][CH2:28][C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[N:21][C:22]([CH3:26])=[CH:23][C:24]=3[CH3:25])[C:13]2=[O:17])=[CH:8][CH:7]=1)C.[OH-].[Na+]>CCO>[CH2:28]([O:27][C:20]1[C:19]([CH2:18][N:12]2[CH2:11][CH2:10][C:9]3[C:14](=[C:15]([Cl:16])[C:6]([OH:5])=[CH:7][CH:8]=3)[C:13]2=[O:17])=[C:24]([CH3:25])[CH:23]=[C:22]([CH3:26])[N:21]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 867237032-{[2-(Benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl diethylcarbamate

Product 1

HCID 867237042-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-7-hydroxy-3,4-dihydroisoquinolin-1(2H)-oneYield 87%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl diethylcarbamate (1g, 14.0 g, 26.8 mmol) and NaOH (10.7 g, 268 mmol) in EtOH (200 mL) was refluxed overnight. The reaction mixture was concentrated under vacuum. To the reaction mixture was added H2O (200 mL) and the solution was acidified with 1 N HCl to pH 3. The reaction mixture was extracted with EtOAc (2×200 mL). The combined organic layers were washed with brine (300 mL), dried over Na2SO4 and concentrated under vacuum. To the residue was added EtOAc (20 mL) and petroleum ether (100 mL). The mixture was filtered and the solids were dried under vacuum to give 2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-7-hydroxy-3,4-dihydroisoquinolin-1(2H)-one (1 h, 9.8 g, 87%) as an off-white solid.

Workup

  1. temperaturewas refluxed overnight
  2. concentrationThe reaction mixture was concentrated under vacuum
  3. additionTo the reaction mixture was added H2O (200 mL)
  4. extractionThe reaction mixture was extracted with EtOAc (2×200 mL)
  5. washThe combined organic layers were washed with brine (300 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under vacuum
  8. additionTo the residue was added EtOAc (20 mL) and petroleum ether (100 mL)
  9. filtrationThe mixture was filtered
  10. customthe solids were dried under vacuum

Sources & evidence

ORD record
ord-4b393e76631b49d7b5ccf3e4e2299690
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

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