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

Participants

Reaction Steps

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

Provenance & Evidence