3-(2-Fluorophenyl)propanenitrile → 2-Fluoro-benzenepropanaMine

Temperature

-15 °C

A solution of 3-(2-fluorophenyl) propionitrile (9.11 g) in tetrahydrofuran (200 mL) was heated to reflux and treated with borane-methyl sulfide complex (6 mL of ˜10 M, 60 mmol). Approximately half of the volume of the reaction was then distilled off. The mixture was then cooled in a −15° C. bath and treated dropwise with ice water (100 mL). The mixture was then concentrated to a solid. The solid was then dissolved in water (100 mL) and treated with concentrated (12 N)HCl (50 mL). The mixture was heated at reflux for 1 h, cooled to ambient temperature, and equilibrated with diethyl ether (100 mL). The organic solution was removed and the resulting aqueous mixture, cooled by the addition of ice, and then basified (pH>10) by treatment with 10 N NaOH (70 mL). The resulting solution was extracted with diethyl ether (100 mL). The diethyl ether extract was removed, dried over anhydrous MgSO4, filtered and concentrated to afford 3-(2-fluorophenyl)propylamine (3.62 g (41% from 2-fluorobenzaldehyde)). GC/MS gave: m/z (rel.int.) 153 (M+, 10), 136 (100), 109 (50), and 83 (22).

1. temperatureto reflux
2. additiontreated with borane-methyl sulfide complex (6 mL of ˜10 M, 60 mmol)
3. distillationApproximately half of the volume of the reaction was then distilled off
4. additiontreated dropwise with ice water (100 mL)
5. concentrationThe mixture was then concentrated to a solid
6. dissolutionThe solid was then dissolved in water (100 mL)
7. additiontreated
8. concentrationwith concentrated (12 N)HCl (50 mL)
9. temperatureThe mixture was heated
10. temperatureat reflux for 1 h
11. temperaturecooled to ambient temperature
12. customThe organic solution was removed
13. temperaturethe resulting aqueous mixture, cooled by the addition of ice
14. extractionThe resulting solution was extracted with diethyl ether (100 mL)
15. extractionThe diethyl ether extract
16. customwas removed
17. dry with materialdried over anhydrous MgSO4
18. filtrationfiltered
19. concentrationconcentrated

ORD record

ord-0fa2ff8e0fab46949a244d8236962e2c

Source dataset

uspto-grants-2011_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07968570B2