1,4-Dicyanobenzene → 4-(1-Aminocyclopropyl)benzonitrile

To a solution of 1,4-dicyanobenzene (3.30 g, 25.8 mmol) in dichloromethane was added titanium(IV) isopropoxide (7.56 mL, 25.8 mmol) followed by ethylmagnesium bromide (3M in ether, 15.5 mL, 46.4 mmol) dropwise (exothermic, gas evolution after one eq of reagent added) and the mixture was stirred at r.t. for 45 min. Borontrifluoride diethyl etherate (5.71 mL, 46.4 mmol) was added and the mixture was stirred at r.t. for 2 h, quenched with NH4Cl and HCl and separated. The aqueous phase was washed once with ether and then the pH was adjusted to 9-10 with 10N NaOH (precipitate formation). The mixture was filtered through celite and the cake washed with water/EtOAc. The phases were separated and the aqueous phase extracted with EtOAc. The organic layers were combined, washed with brine, dried over Na2SO4, filtered and concentrated in vacuo to give the desired product as a viscous oil which solidified at −20° C. The crude was used directly without further purification.

1. stirringthe mixture was stirred at r.t. for 2 h
2. customquenched with NH4Cl and HCl
3. customseparated
4. washThe aqueous phase was washed once with ether
5. filtrationThe mixture was filtered through celite
6. washthe cake washed with water/EtOAc
7. customThe phases were separated
8. extractionthe aqueous phase extracted with EtOAc
9. washwashed with brine
10. dry with materialdried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated in vacuo

ORD record

ord-9b966cc15896485baa078ea8c1bf4338

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08969394B2