Hydrochloric Acid → 4-(Aminomethyl)-2-bromobenzonitrile

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Reaction Steps

To a suspension of 2-bromo-4-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]benzonitrile (8.0 g, 23.5 mmol) in EtOH (150 mL) was added hydrazine hydrate (85%, 2.76 g). The mixture was refluxed for 3 h. At room temperature 2 N HCl (60 mL) was added (pH=3), and the mixture was filtered and rinsed with water (50 mL×4). The filtrate was evaporated to about 150 mL and filtered again. After addition of NaHCO3 to adjust the pH=9, the filtrate was extracted with CH2Cl2 (100 mL×3). The combined extracts were washed with brine and dried over anhydrous sodium sulfate. After removing the solvent, 1N HCl in MeOH (50 mL) was added and the solvent was evaporated to afford crude material as a white solid. Recrystallization from MeOH-Et2O yielded 4.3 g of the product, 4-(aminomethyl)-2-bromobenzonitrile (yield: 75.8%). 1H NMR (400 MHz, D2O) δ 4.21 (S, 2H), 7.43 (dd, J=8.0 Hz, J=1.2 Hz, 1H), 7.71 (d, J=8.0 Hz, 2H); 13C NMR (100 MHz, D2O): δ42.3, 115.5, 118.0, 125.6, 128.4, 133.4, 135.5, 139.9; HPLC: retention time: 4.709 min; purity: 99.7%.

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