Chlorosuccinimide → 2-Amino-3-chloro-5-fluorobenzonitrile

Temperature

80 °C

To a solution of 2-amino-5-fluorobenzonitrile (15.0 g, 110 mmol) in anhydrous acetonitrile (300 mL) was added N-chlorosuccinimide (16.0 g, 120 mmol) portionwise. The reaction mixture was heated at 80° C. for 18 hours under nitrogen. The resultant mixture was allowed to cool, concentrated under reduced pressure and then partitioned between EtOAc and water. The aqueous layer was extracted with ethyl acetate and the combined organic extracts were dried, filtered and concentrated under reduced pressure. The crude residue was purified by silica gel flash chromatography (10-20% diethyl ether in pentane) to afford the title compound as an off-white solid (9.6 g, 51% yield). 1H NMR (300 MHz, CDCl3): δ 7.27 (dd, J=7.9, 2.9 Hz, 1H), 7.08 (dd, J=7.6, 2.9 Hz, 1H), 4.67 (br s, 2H).

1. temperatureto cool
2. concentrationconcentrated under reduced pressure
3. custompartitioned between EtOAc and water
4. extractionThe aqueous layer was extracted with ethyl acetate
5. customthe combined organic extracts were dried
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe crude residue was purified by silica gel flash chromatography (10-20% diethyl ether in pentane)

ORD record

ord-447a0268d635451a9f75668571e1900b

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09309240B2