反应详情

温度

55 °C

To a solution of 3,5-bis(trifluoromethyl)benzoic acid (3.04 g) and pyridine (0.030 ml) in tetrahydrofuran (9 ml) was added dropwise oxalyl chloride. (1.80 g) over 5 minutes, and the reaction mixture was heated at 55° C. with stirring for one hour. After cooling, the solution was added dropwise to a solution of (2R)-2-(4-methoxybenzyl)-4-benzylpiperazine (3.47 g) and triethylamine (3.55 g) in dichloromethane (35 ml) below 5C over 30 minutes under nitrogen atmosphere. The reaction mixture was stirred at room temperature for one hour, and concentrated under reduced pressure. To the residue were added ethyl acetate (40 ml) and water (20 ml) with stirring. The organic layer was separated, washed with brine, and dried over magnesium sulfate. After removal of the solvent by evaporation, the resulting residue was purified by column chromatography on silica gel (70 g) using a mixed solvent of toluene and ethyl acetate (5:1). The fractions containing the objective compound were collected and evaporated under reduced pressure to give (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(4-methoxybenzyl)-4-benzylpiperazine (5.03 g) as syrup.

1. temperatureAfter cooling
2. stirringThe reaction mixture was stirred at room temperature for one hour
3. concentrationconcentrated under reduced pressure
4. additionTo the residue were added ethyl acetate (40 ml) and water (20 ml)
5. stirringwith stirring
6. customThe organic layer was separated
7. washwashed with brine
8. dry with materialdried over magnesium sulfate
9. customAfter removal of the solvent
10. customby evaporation
11. customthe resulting residue was purified by column chromatography on silica gel (70 g)
12. additionThe fractions containing the objective compound
13. customwere collected
14. customevaporated under reduced pressure