Chlorosuccinimide → 4-Amino-3-chloro-5-fluorobenzonitrile

A solution of 4-amino-3-fluorobenzonitrile (25.13 g, 185 mmol) and NCS (24.65 g, 185 mmol) in acetonitrile (500 mL) was stirred at 86° C. (reflux) for 5 h. LCMS showed ˜17% of starting material remained. Additional NCS (0.2 eq) was added and the reaction was stirred for 1 h. The reaction was partly concentrated and the residue was partitioned between 5% NaOH (100 mL) and EtOAc. The aqueous layer was back extracted with EtOAc. The organic extracts were dried over Na2SO4 and concentrated to a pink solid. The NMR spectrum showed some of the succinimate side product still remained. The crude product was washed with H2O and air dried to give the desired product as a beige solid. This product was used in the next step without any further purification. MS (m/z) 171.1 (M+H+).

1. temperature(reflux) for 5 h
2. concentrationThe reaction was partly concentrated
3. customthe residue was partitioned between 5% NaOH (100 mL) and EtOAc
4. extractionThe aqueous layer was back extracted with EtOAc
5. dry with materialThe organic extracts were dried over Na2SO4
6. concentrationconcentrated to a pink solid
7. washThe crude product was washed with H2O and air
8. customdried

ORD record

ord-dd9f209edca948f0a9f8e3a843429da7

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09187464B2