反应详情

A mixture of 4-cyano-3-methyl-benzoic acid from Example E6 (750 mg, 4.6 mmol) and thionyl chloride (1.02 ml, 14.0 mmol) in toluene (40 ml) was heated at reflux for 2 h. After cooling at room temperature, solvents were re-moved in vacuo and azeotroped with toluene. The residue was redissolved in dichloromethane (25 ml) then 4-trifluoromethylaniline hydrochloride (1.11 g, 5.6 mmol) in dichloromethane (5 ml) and triethylamine (1.95 ml, 14.0 mmol) was added. The mixture was stirred at room temperature for 2 days, washed with brine, dried and concentrated in vacuo. The residue was purified by flash chromatography on silica gel through an isolute (eluant; 20% EtOAc:80% cyclohexane) to yield the title compound (1.13 g, 80%).

1. temperaturewas heated
2. temperatureat reflux for 2 h
3. customazeotroped with toluene
4. dissolutionThe residue was redissolved in dichloromethane (25 ml)
5. washwashed with brine
6. customdried
7. concentrationconcentrated in vacuo
8. customThe residue was purified by flash chromatography on silica gel through an isolute (eluant; 20% EtOAc:80% cyclohexane)