71% |
tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 120℃; for 2h;Product distribution / selectivity; |
Example 8 2-Chloro-4-fluoro-3-methylbenzonitrile (198RL18) 3-Bromo-2-chloro-6-fluorotoluene (7.0 g, 31 mmol), zinc cyanide (3.7 g, 31 mmol) and tetrakis(triphenylphosphine)palladium(0) (1.81 g, 1.56 mmol) was added to a flask under argon atmosphere. Dry DMF (35 mL) was added and the reaction mixture was stirred under argon at 120 C. The reaction was monitored by GC-MS and full conversion was observed after 2 hours. The mixture was diluted with dichloromethane (300 mL), washed with water (100 mL) and 4% magnesium sulfate solution (100 mL), dried over magnesium sulphate, filtered, and evaporated to give a clear oil. The product was further purified by column chromatography on silica gel using n-heptane/ethyl acetate (9:1) giving a white solid (3.79 g, 71%). 1H-NMR (CDCl3) delta 7.43 (dd, 1H, J=5.6, 8.8, Ar-H), 6.87 (t, 1H, J=8.8, Ar-H), 2.36 (d, 3H, J=2.4, CH3). |
42% |
tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 200℃; for 0.0416667h;Microwave;Product distribution / selectivity; |
Example 3 2-Chloro-4-fluoro-3-methylbenzonitrile (165RL87a) 3-Bromo-2-chloro-6-fluorotoluene 165RL91 (173 mg, 0.78 mmol), zinc cyanide (91 mg, 0.78 mmol) and tetrakis(triphenylphosphine)palladium(0) (27 mg, 23 mumol) was charged in a vial, DMF (1 mL) added, and the mixture irradiated for 150 sec at 200 C. in a microwave oven. Diethyl ether (30 ml) was added and the reaction mixture washed with magnesium sulphate (4% solution, 3*20 mL) followed by brine (20 mL). The organic layer was dried and evaporated. The product was further purified by column chromatography on silica gel using n-heptane/ethyl acetate (9:1) giving a white solid (55 mg, 42%). GC/MS m/z 169 [M+H]+. 1H-NMR (CDCl3, 300 MHz) delta 7.43 (dd, 1H, J=5.6, 8.8, Ar-H), 6.87 (t, 1H, J=8.8, Ar-H), 2.36 (d, 3H, J=2.4, CH3). |