Phthalimide → 4-(2-Aminoethyl)benzonitrile

A mixture of phthalimide (20.0 g) and triphenylphosphine (35.65 g) was added dropwise to a mixture of 4-(2-hydroxyethyl)benzonitrile (20.0 g) and diethylazodicarboxylate (21.4 ml) in THF (650 ml) with stirring over one hour. The mixture was stirred at ambient temperature for 4 days. The solvent was removed under reduced pressure. Methanol (500 ml) and hydrazine hydrate (13 ml) were added to the residue and the mixture was boiled under reflux with stirring for 5 hours. The solvent was removed under reduced pressure and aqueous acetic acid (420 ml of glacial acetic acid in 1030 ml of water) was added to the residue. This mixture was stirred for 1 hour and then filtered. The filtrate was added to ice and basified with solid potassium hydroxide. The mixture was extracted with dichloromethane to give an oil which was purified by flash column chromatography to give 4-(2-aminoethyl)benzonitrile, as an oil. A sample was dissolved in ethereal hydrogen chloride to give the hydrochloride salt, m.p. 211-213° C.

1. stirringThe mixture was stirred at ambient temperature for 4 days
2. customThe solvent was removed under reduced pressure
3. additionMethanol (500 ml) and hydrazine hydrate (13 ml) were added to the residue
4. temperatureunder reflux
5. stirringwith stirring for 5 hours
6. customThe solvent was removed under reduced pressure and aqueous acetic acid (420 ml of glacial acetic acid in 1030 ml of water)
7. additionwas added to the residue
8. stirringThis mixture was stirred for 1 hour
9. filtrationfiltered
10. additionThe filtrate was added to ice and basified with solid potassium hydroxide
11. extractionThe mixture was extracted with dichloromethane
12. customto give an oil which
13. customwas purified by flash column chromatography

ORD record

ord-21a3e633aa0540f0bc099c8d1f091fc9

Source dataset

uspto-grants-2001_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06326500B1