Dimethylformamide → 3-Amino-4-cyanobenzoic acid

Temperature

100 °C

To a solution of 3-amino-4-bromo-benzoic acid (6.0 g, 276 mmol) in dimethyl formamide (30 ml), was added sequentially at ambient temperature zinc cyanide (11.66 g, 99.4 mmol) and tetrakis(triphenylphosphine)palladium (9.57 g, 8.28 mmol). The mixture was heated to 100° C. for 14 hours. The reaction mixture was allowed to cool to ambient temperature before the sequential addition of more zinc cyanide (0.65 g, 5.54 mmol) and tetrakis(triphenylphosphine)palladium (1.9 g, 1.64 mmol) at ambient temperature. The mixture was heated to 100° C. for 1 more hour. The reaction mixture was allowed to cool to ambient temperature and was quenched by addition of a mixture of toluene and aqueous ammonia (1M). The phases were separated and the aqueous layer was extracted with toluene. The combined organic phases were dried over sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel (eluent: ethyl acetate/cyclohexane 1:2 to 1:0) to give 3-amino-4-cyano-benzoic acid (2.94 g, 67% yield).

1. temperatureThe mixture was heated to 100° C. for 1 more hour
2. temperatureto cool to ambient temperature
3. customwas quenched by addition of a mixture of toluene and aqueous ammonia (1M)
4. customThe phases were separated
5. extractionthe aqueous layer was extracted with toluene
6. dry with materialThe combined organic phases were dried over sodium sulfate
7. concentrationconcentrated
8. customThe residue was purified by column chromatography on silica gel (eluent: ethyl acetate/cyclohexane 1:2 to 1:0)

ORD record

ord-1218ea023ea0493595503e3cb5130471

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08389767B2