Sodium Hydroxide → 6-Bromo-2-(2-phenylpropyl)-isoquinolin-1-one

HRID 1037619Notes

Reaction equation

HRID 1037619 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([OH:12])=[N:7][CH:6]=[CH:5]2.Br[CH2:14][CH:15]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH3:16].[OH-].[Na+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1.C(OCC)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([CH2:14][CH:15]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH3:16])[CH:6]=[CH:5]2

Participants

7

Reactant 3

HCID 14798Sodium HydroxideHCID 978131-Bromo-2-phenylpropaneHCID 178517609HCID 178517609, compound

Product 1

HCID 667325006-Bromo-2-(2-phenylpropyl)-isoquinolin-1-oneYield 74%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Procedure

6-Bromo-1-hydroxyisoquinoline (150 mg, 0.67 mmol, 1.0 equiv), tetrabutylammonium bromide (25 mg, 0.07 mmol, 0.1 equiv), and 1-bromo-2-phenylpropane (160 uL, 0.8 mmol, 1.2 equiv) were combined in toluene (10 mL) and treated with 50% aq. NaOH (2 mL), and the resulting mixture was stirred rapidly at ambient temperature for 48 hours, then heated at 60° C. for 24 h. The mixture was diluted with diethyl ether and washed with water and brine. The organic phase was dried over Na2SO4. Concentration and purification of the residue using silica gel flash chromatography (2-12% EtOAc/hex.) gave white crystals of 6-bromo-2-(2-phenylpropyl)-isoquinolin-1-one (169 mg, 0.49 mmol, 74%). This isoquinolinone (169 mg, 0.49 mmol) was converted, via Methods 1 and 2, to compound 5 (65 mg, 43%) which was isolated as white solid. [M−H]−=306.1 m/z. Activity: B

Workup

  1. temperatureheated at 60° C. for 24 h
  2. washwashed with water and brine
  3. dry with materialThe organic phase was dried over Na2SO4
  4. concentrationConcentration and purification of the residue

Sources & evidence

ORD record
ord-0c266cc3311241e79160ef9ae6296e53
Source dataset
uspto-grants-2013_10
Patent number
US08546564B2

Reaction notes

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