General procedure for the synthesis of 6-cyanoisoindolin-1-one from methyl 2-(bromomethyl)-5-cyanobenzoate:
A) Synthesis of 3-oxoisoindoline-5-carbonitrile
Methyl 2-(bromomethyl)-5-cyanobenzoate (5.7 g) was dissolved in methanol (100 mL) and 28% ammonia (109 mL) was added to this solution. The reaction mixture was stirred at room temperature for 1 hour. Upon completion of the reaction, the solvent was removed by concentration under reduced pressure. Water was added to the concentrated residue and the precipitated solid was collected by filtration and washed with ethanol to give the final 6-cyanoisoindolin-1-one (3.12 g). Mass spectrometry (API+) analysis resulted in a measured value of 159.1 (M + 1).
