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

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 concentrated to about 150 mL and filtered again. After addition of NaHCO3 to pH=9, the filtrate was extracted with CH2Cl2 (100 mL×3). The combined extract was washed with brine, dried over anhydrous sodium sulfate. After removing the solvent, 1N HCl in MeOH (50 mL) was added and the solvent was concentrated 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, 2 H), 7.43 (dd, J=8.0 Hz, J=1.2 Hz, 1 H), 7.71 (d, J=8.0 Hz, 2 H); 13C NMR (100 MHz, D2O): δ 42.3, 115.5, 118.0, 125.6, 128.4, 133.4, 135.5, 139.9; HPLC: retention time: 4.709 min; purity: 99.7%.

1. temperatureThe mixture was refluxed for 3 h
2. filtrationthe mixture was filtered
3. washrinsed with water (50 mL×4)
4. concentrationThe filtrate was concentrated to about 150 mL
5. filtrationfiltered again
6. additionAfter addition of NaHCO3 to pH=9
7. extractionthe filtrate was extracted with CH2Cl2 (100 mL×3)
8. extractionThe combined extract
9. washwas washed with brine
10. dry with materialdried over anhydrous sodium sulfate
11. customAfter removing the solvent, 1N HCl in MeOH (50 mL)
12. additionwas added
13. concentrationthe solvent was concentrated
14. customto afford crude material as a white solid
15. customRecrystallization from MeOH-Et2O

ORD record

ord-702a1429686d41349e61a38db8465d26

Source dataset

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08067408B2