Phenethyl bromide → 6-Bromo-2-phenethyl-isoquinolin-1-one

HRID 1037617Notes

Reaction equation

HRID 1037617 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.[CH2:13](Br)[CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[OH-].[Na+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1.CC(OC)(C)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH:6]=[CH:5]2

Participants

7

Reactant 3

HCID 7666Phenethyl bromideHCID 14798Sodium HydroxideHCID 178517609HCID 178517609, compound

Product 1

HCID 667328906-Bromo-2-phenethyl-isoquinolin-1-oneYield 51.5%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 1140TolueneSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

6-Bromo-1-hydroxyisoquinoline (300 mg, 1.34 mmol, 1.0 equiv), tetrabutylammonium bromide (50 mg, 0.13 mmol, 0.10 equiv), and phenethyl bromide (220 uL, 1.6 mmol, 1.2 eq) were combined in toluene (14 mL), treated with 50% aq. NaOH (3 mL) after which the resulting mixture stirred rapidly at ambient temperature. After stirring for an additional 14 hours, the mixture was diluted with MTBE and washed with water, saturated NaHCO3, and brine. The organic phase was dried over Na2SO4. Addition of silica gel, concentration, and purification of the residue using flash silica gel chromatography (gradient of 3-15% ethyl acetate/hexanes) provided 6-bromo-2-phenethyl-isoquinolin-1-one (225 mg, 0.69 mmol, 51%) as a white solid. This isoquinolinone (225 mg, 0.69 mmol) was then converted, via Methods 1 and 2, to compound 3 (95 mg, 47%) and isolated as a white solid. [M−H]−=292.1 m/z. Activity: A

Workup

  1. stirringAfter stirring for an additional 14 hours
  2. washwashed with water, saturated NaHCO3, and brine
  3. dry with materialThe organic phase was dried over Na2SO4
  4. additionAddition of silica gel, concentration, and purification of the residue

Sources & evidence

ORD record
ord-71abecf9fc52475687acbd0f5e7fb48c
Source dataset
uspto-grants-2013_10
Patent number
US08546564B2

Reaction notes

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