反应详情

Oxalyl chloride (0.36 ml, 3.3 mmol) was added to a solution of 4-carboxymethyl-3-methyl-benzoic acid methyl ester from Example E32 (687 mg, 3.3 mmol) in dichloromethane (20 ml) and few drops of DMF. The mixture was stirred for 3 h at room temperature, concentrated in vacuo and azeotroped with toluene. The residue was dissolved in dichloromethane (10 ml) and added to a solution of 1-cyclobutylmethyl-piperazine dihydrochloride (750 mg, 3.3 mmol) in dichloromethane (10 ml) and DIEA (1.73 ml, 9.9 mmol) at 0° C. The mixture was stirred for 20 h at room temperature and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (eluant; 3% methanol:97% dichloromethane) to yield the title compound (528 mg, 46%).

1. concentrationconcentrated in vacuo
2. customazeotroped with toluene
3. dissolutionThe residue was dissolved in dichloromethane (10 ml)
4. stirringThe mixture was stirred for 20 h at room temperature
5. concentrationconcentrated in vacuo
6. customThe residue was purified by flash chromatography on silica gel (eluant; 3% methanol:97% dichloromethane)