Hydrochloric Acid → (2-Chloro-3-fluorophenyl)methanamine

Temperatur

70 °C

BH3.THF in THF (1.0 M, 50.0 ml) was carefully added into the THF (40.0 ml) solution of 2-chloro-3-fluorobenzonitrile (662 mg, 4.17 mmol) at rt. The resulting mixture was heated at 70° C. under an atmosphere of nitrogen for 16 h. After cooling to ambient temperature, conc. HCl (5.18 ml, 62.5 mmol) was added slowly. The combined mixture was heated at 70° C. for 30 min. After that time, the mixture was concentrated in vacuo to remove most of solvent, water (20 ml) was added, and the mixture was extracted with Et2O (3×30 ml). The extracts were washed with water (20 ml). The combined aqueous layers were basified by saturated Na2CO3 until pH=9 and extracted with EtOAc (3×50 ml). These EtOAc extracts were washed with brine (50 ml) dried over MgSO4, filtered, and concentrated in vacuo to give the title compound as colorless oil. 1H NMR (400 MHz, CDCl3): δ=1.67 (brs, 2H), 3.97 (s, 2H), 7.03-7.09 (m, 1H), 7.17-7.26 (m, 2H). MS(ES+): m/z=160.14/162.09 (64/32) [MH+]. HPLC: tR=0.40 & 0.70 min (polar—5 min, ZQ3; peak splitting).

1. temperatureAfter cooling to ambient temperature
2. temperatureThe combined mixture was heated at 70° C. for 30 min
3. concentrationAfter that time, the mixture was concentrated in vacuo
4. customto remove most of solvent, water (20 ml)
5. additionwas added
6. extractionthe mixture was extracted with Et2O (3×30 ml)
7. washThe extracts were washed with water (20 ml)
8. extractionextracted with EtOAc (3×50 ml)
9. washThese EtOAc extracts were washed with brine (50 ml)
10. dry with materialdried over MgSO4
11. filtrationfiltered
12. concentrationconcentrated in vacuo

ORD-Eintrag

ord-f68fd13cda724ac59048d6b3d132179f

Quelldatensatz

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08178668B2