Hydrochloric Acid → 3-(Aminomethyl)-5-bromobenzonitrile

To a suspension of 3-bromo-5-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]benzonitrile (3.50 g, 10.3 mmol) in EtOH (60 mL) was added N2H4H2O (85%, 1.31 g). The mixture was refluxed for 3 h. At room temperature 2 N HCl (20 mL) was added (pH=3), and the mixture was filtered and rinsed with water (20 mL×2). The filtrate was concentrated to about 50 mL and filtered again. After addition of NaHCO3 (pH=9), the filtrate was extracted with CH2Cl2 (50 mL×3). The combined extracts were washed with brine, dried over anhydrous sodium sulfate, and concentrated to give a mixture of colorless solid and colorless oil. 2N HCl in MeOH (50 mL) was added and concentrated to afford crude material as a white solid. Recrystallization from MeOH-Et2O yielded the product 3-(aminomethyl)-5-bromobenzonitrile (1.40 g, 55%) as colorless fine needles. 1H NMR (400 MHz, D2O): δ 7.92 (m, 1 H), 7.84 (m, 1 H), 7.69 (m, 1 H), 4.11 (s, 2 H); 13C NMR (400 MHz, D2O): δ 137.1, 135.9, 135.8, 131.7, 123.0, 117.7, 113.8, 42.0; MS: m/z 209.0 (M+−HCl); HPLC: retention time: 9.313 min; purity: 98.4%.

1. temperatureThe mixture was refluxed for 3 h
2. filtrationthe mixture was filtered
3. washrinsed with water (20 mL×2)
4. concentrationThe filtrate was concentrated to about 50 mL
5. filtrationfiltered again
6. additionAfter addition of NaHCO3 (pH=9)
7. extractionthe filtrate was extracted with CH2Cl2 (50 mL×3)
8. washThe combined extracts were washed with brine
9. dry with materialdried over anhydrous sodium sulfate
10. concentrationconcentrated
11. customto give
12. additiona mixture of colorless solid and colorless oil
13. concentrationconcentrated
14. customto afford crude material as a white solid
15. customRecrystallization from MeOH-Et2O

ORD record

ord-9b1470e6489247e1935f098ec9610025

Source dataset

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08067408B2