* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
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 <n="29"/>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 1000C 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 (IM). 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, 67percent yield).
A solution of ethyl 3-amino-4-cyano-benzoate (Step 2) (140 mg, 0.74 mmol) in THF (6 mL) was treated with a solution of lithium hydroxide monohydrate (47 mg, 1.10 mmol) in water (3ml), and the mixture stirred at ambient temperature for 2 hrs. The THF was removed in vacuo and the aqueous residue washed with EtOAc (30 mL) to remove any unreacted starting material. The aqueous was then adjusted to pH3 with citric acid solution (IM), and extracted with EtOAc (20 mL). The organic extracts were washed with brine (20 mL), dried (MgSO4), filtered and reduced in vacuo to give the title compound as a yellow solid (60 mg), 1H NMR (300.073 MHz, d6-DMSO) delta 6.27 (s, 2H), 7.04 - 7.08 (m, IH), 7.38 - 7.40 (m, IH), 7.47 (d, IH), 13.03 (s, IH), m/z 161 (M-H)".
Step 3: 3-amino-4-cyano-benzoic acidA solution of ethyl 3-amino-4-cyano-benzoate (Step 2) (140 mg, 0.74 mmol) in THF (6 mL) was treated with a solution of lithium hydroxide monohydrate (47 mg, 1.10 mmol) in water (3ml), and the mixture stirred at ambient temperature for 2 hrs. The THF was <n="150"/>removed in vacuo and the aqueous residue washed with EtOAc (30 mL) to remove any unreacted starting material. The aqueous was then adjusted to pH3 with citric acid solution (IM), and extracted with EtOAc (20 mL). The organic extracts were washed with brine (20 mL), dried (MgSO4), filtered and reduced in vacuo to give the title compound as a yellow solid (60 mg), eta NMR (300.073 MHz, DMSO-Cl6) delta 6.27 (s, 2H), 7.04 - 7.08 (m, IH),7.38 - 7.40 (m, IH), 7.47 (d, IH), 13.03 (s, IH), m/z 161 (M-Hy.
tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 20 - 100℃; for 15h;
To a solution of <strong>[2840-29-1]3-amino-4-bromo-benzoic acid</strong> (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 100C for 14 hours. The reaction mixture was allowed to cool to <n="29"/>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 1000C 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 (IM). 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).
With thionyl chloride; In toluene; for 2.0h;Heating / reflux;
Thionyl chloride (4.4 g, 37 mmol) was added to a solution of 3-amino-4-cyano- benzoic acid (2.0 g, 9.25 mmol) (Example 6.1) in toluene (12 ml). The reaction mixture was heated to reflux for 2 hours. Excess thionyl chloride and toluene were distilled off under reduced pressure. The product was used without further purification.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
