反应详情

1.00 g (6.43 mmol) of methyl 2-amino-3-hydroxypropionate hydrochloride and 960 mg (14.1 mmol) of imidazole were dissolved in 10 ml of dichloromethane. 10 ml of a solution of 1.07 g (7.07 mmol) of t-butyldimethylchlorosilane in dichloromethane was added dropwise to the obtained solution under cooling with ice, and they were stirred at room temperature for 1 hour. After concentrating under reduced pressure, ethyl acetate was added to the residue. The reaction mixture was washed with saturated aqueous ammonium chloride solution, then dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in 10 ml of dichloromethane. 1.35 ml (9.65 mmol) of triethylamine and 0.97 ml (7.72 mmol) of 1-piperidinecarbonyl chloride were added dropwise to the obtained solution under cooling with ice, and they were stirred at room temperature overnight. 20 ml of chloroform was added to the reaction mixture, and they were stirred at 50° C. for 3 hours and then concentrated under reduced pressure. The residue was dissolved in 15 ml of methanol. 10 ml of 2 N hydrochloric acid was added dropwise to the obtained solution under cooling with ice, and they were stirred at room temperature for 2 hours. After the concentration under reduced pressure, ethyl acetate was added to the residue. The product was washed with 1 N aqueous hydrochloric acid solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue thus obtained was purified by the silica gel chromatography (dichloromethane:methanol=1:0 to 9:1) to obtain the title compound.

1. temperatureunder cooling with ice, and they
2. concentrationAfter concentrating under reduced pressure, ethyl acetate
3. additionwas added to the residue
4. washThe reaction mixture was washed with saturated aqueous ammonium chloride solution
5. dry with materialdried over anhydrous magnesium sulfate
6. concentrationconcentrated under reduced pressure
7. dissolutionThe residue was dissolved in 10 ml of dichloromethane
8. temperatureunder cooling with ice, and they
9. stirringwere stirred at room temperature overnight
10. stirringwere stirred at 50° C. for 3 hours
11. concentrationconcentrated under reduced pressure
12. dissolutionThe residue was dissolved in 15 ml of methanol
13. addition10 ml of 2 N hydrochloric acid was added dropwise to the obtained solution
14. temperatureunder cooling with ice, and they
15. stirringwere stirred at room temperature for 2 hours
16. concentrationAfter the concentration under reduced pressure, ethyl acetate
17. additionwas added to the residue
18. washThe product was washed with 1 N aqueous hydrochloric acid solution
19. dry with materialdried over anhydrous magnesium sulfate
20. concentrationconcentrated under reduced pressure
21. customThe residue thus obtained
22. customwas purified by the silica gel chromatography (dichloromethane:methanol=1:0 to 9:1)