反应详情

温度

110 °C

A mixture of 2-(difluoro-methyl)-6-methyl-4-morpholin-4-yl-benzoic acid ethyl ester (0.30 g, 1.00 mmol), 4-chlorobenzylamine (1.42 g, 10.0 mmol) and trimethylaluminium (2M in toluene) (3.50 ml, 7.00 mmol) in toluene (10 ml) is heated at 110° C. for 18 h. After completion of the reaction (monitored by TLC), a 2M aqueous solution of sodium hydroxide is carefully added and the mixture is extracted with ethyl acetate (2×15 ml). The combined organic layers are washed with 2M aqueous solution of sodium hydroxide (10 ml), brine (10 ml) and dried over sodium sulfate. The solvent is evaporated to get the crude product, which is purified by column chromatography (silica gel, 30% ethyl acetate/cyclohexane) to afford N-[(4-chlorophenyl)-methyl]-2-(difluoro-methyl)-6-methyl-4-morpholin-4-yl-benzamide (example 20) (0.05 g, 0.13 mmol, 13%). [M+H]+ 395.1.

1. customAfter completion of the reaction (monitored by TLC)
2. extractionthe mixture is extracted with ethyl acetate (2×15 ml)
3. washThe combined organic layers are washed with 2M aqueous solution of sodium hydroxide (10 ml), brine (10 ml)
4. dry with materialdried over sodium sulfate
5. customThe solvent is evaporated
6. customto get the crude product, which
7. customis purified by column chromatography (silica gel, 30% ethyl acetate/cyclohexane)