反应详情

温度

90 °C

A mixture of 3,3-dimethyl-4-(2-propynyl)morpholine hydrochloride (0.24 g), 37% aqueous formaldehyde (0.16 ml), (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)piperazine (0.57 g), copper(II) sulfate pentahydrate (5 mg) and potassium iodide (20 mg) in 1,4-dioxane (0.7 ml) was stirred at 90° C. for 1 hour. After being cooled to room temperature, the mixture was poured into ice-water and the aqueous mixture was made alkaline with saturated aqueous sodium hydrogen carbonate solution. The resulting mixture was extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel using a mixed solvent of dichloromethane and methanol (40:1). The fractions containing the objective compound was collected and evaporated under reduced pressure and treated with 4N hydrogen chloride in ethyl acetate solution. The resulting mixture was evaporated under reduced pressure and the residue was recrystallized from a mixture of acetone and water to give colorless crystals of (2R)-1-[3,5-bis(trifluoromethyl) benzoyl]-2-(3,4-dimethylbenzyl)-4-[4-(3,3-dimethyl-morpholino)-2-butynyl]piperazine dihydrochloride (0.64 g).

1. temperatureAfter being cooled to room temperature
2. extractionThe resulting mixture was extracted with ethyl acetate
3. washThe extract was washed with brine
4. dry with materialdried over magnesium sulfate
5. customevaporated under reduced pressure
6. customThe residue was purified by column chromatography on silica gel using a mixed solvent of dichloromethane and methanol (40:1)
7. additionThe fractions containing the objective compound
8. customwas collected
9. customevaporated under reduced pressure
10. additiontreated with 4N hydrogen chloride in ethyl acetate solution
11. customThe resulting mixture was evaporated under reduced pressure
12. customthe residue was recrystallized from a mixture of acetone and water