反应详情

温度

80 °C

1.40 g of 1-acetoxy-1-(3-chlorophenyl)-2-(2-methanesulfonyloxyethoxy)ethane was dissolved in 7 ml of N,N-dimethylformamide. To the solution were added 0.69 ml of N-methylpiperazine and 1.03 g of potassium carbonate. The mixture was stirred for 3 hours at 80° C. The reaction mixture was cooled and added to a mixture of 30 ml of ice water and 30 ml of diethyl ether. The organic layer was separated. The aqueous layer was extracted with 20 ml of diethyl ether. The extract was combined with the previously separated organic layer. The combined organic layer was washed with water and a saturated aqueous sodium chloride solution in this order, and dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure. The residue thus obtained was mixed with 7 ml of methanol and 45 mg of sodium methoxide. The mixture was allowed to stand overnight at room temperature. The solvent was removed by distillation under reduced pressure. To the residue thus obtained were added 20 ml of ethyl acetate and 10 ml of water. The organic layer was separated. The aqueous layer was extracted with 20 ml of ethyl acetate. The extract was combined with the previously separated organic layer. The combined organic layer was washed with a saturated aqueous sodium chloride solution and then purified by column chromatography (eluant: chloroform/methanol=10/1). To the resulting oily product were added 10 ml of ethanol and 1.2 ml of a 6N dry hydrogen chloride-ethanol solution in this order. To the resulting mixture was added 10 ml of diethyl ether. The mixture was stirred for 30 minutes. The resulting crystals were collected by filtration, washed with a mixture of 2 ml of ethanol and 2 ml of diethyl ether, and dried to obtain 770 mg of 1-(3-chlorophenyl)-2-[2-(4-methylpiperazin-1-yl)ethoxy]ethanol dihydrochloride (compound No. 158).

1. temperatureThe reaction mixture was cooled
2. customThe organic layer was separated
3. extractionThe aqueous layer was extracted with 20 ml of diethyl ether
4. washThe combined organic layer was washed with water
5. dry with materiala saturated aqueous sodium chloride solution in this order, and dried over anhydrous magnesium sulfate
6. customThe solvent was removed by distillation under reduced pressure
7. customThe residue thus obtained
8. waitto stand overnight at room temperature
9. customThe solvent was removed by distillation under reduced pressure
10. customTo the residue thus obtained
11. customThe organic layer was separated
12. extractionThe aqueous layer was extracted with 20 ml of ethyl acetate
13. washThe combined organic layer was washed with a saturated aqueous sodium chloride solution
14. custompurified by column chromatography (eluant: chloroform/methanol=10/1)
15. additionTo the resulting oily product were added 10 ml of ethanol and 1.2 ml of a 6N dry hydrogen chloride-ethanol solution in this order
16. additionTo the resulting mixture was added 10 ml of diethyl ether
17. stirringThe mixture was stirred for 30 minutes
18. filtrationThe resulting crystals were collected by filtration
19. washwashed with a mixture of 2 ml of ethanol and 2 ml of diethyl ether
20. customdried