反应详情

温度

2.5 °C

47.3 g (250 mmol) of (S)-2-tert.-butoxycarbonylamino-propionic acid (Fluka) were dissolved in 560 ml of ethyl acetate (Fluka) while stirring and under argon, cooled to 0-5° C. and treated with 31.0 ml (250 mmol) of pivaloyl chloride (d=98; Fluka). The light yellowish solution was treated dropwise within 30 minutes with 35.0 ml (250 mmol) of triethylamine (d=0.726; Fluka), with the temperature being held in the range of 0-5° C. A white suspension formed. The white precipitate was filtered off through a pre-cooled, sintered glass filter (G3) and the filter cake was washed with 140 ml of cold ethyl acetate (0 to 5° C.). To the combined filtrates, a light yellow solution, were added 55.9 g (17. HCl; 250 mmol) of ethyl (piperidin-4-yloxy)-acetate hydrochloride and 66.6 g of K3PO4.3H2O (250 mmol; Merck). The white suspension was treated with 500 ml of deionised water at 5 to 10° C. under argon and while stirring vigorously, with the temperature rising to 20° C. The colourless two-phase system was stirred at 20 to 25° C. for two hours. The aqueous phase was separated and the organic phase was washed with 500 ml of a 1M sodium bicarbonate solution. The organic phase was dried over about 50 g of sodium sulphate, filtered and the filter cake was washed with about 100 ml of ethyl acetate. The combined filtrates were evaporated in a rotary evaporator at 50°/20 mbar, giving 85.5 g (95 wt. %) of ethyl (S)-[1-(2-tert.-butoxycarbonylamino-propionyl)-piperidin-4-yloxy]-acetate as a crude product in the form of a clear, yellowish oil (HPLC analysis: 88.9% (area).

1. custombeing held in the range of 0-5° C
2. customA white suspension formed
3. filtrationThe white precipitate was filtered off through a pre-cooled, sintered glass
4. filtrationfilter (G3)
5. washthe filter cake was washed with 140 ml of cold ethyl acetate (0 to 5° C.)
6. stirringwhile stirring vigorously, with the temperature
7. customrising to 20° C
8. stirringThe colourless two-phase system was stirred at 20 to 25° C. for two hours
9. customThe aqueous phase was separated
10. washthe organic phase was washed with 500 ml of a 1M sodium bicarbonate solution
11. dry with materialThe organic phase was dried over about 50 g of sodium sulphate
12. filtrationfiltered
13. washthe filter cake was washed with about 100 ml of ethyl acetate
14. customThe combined filtrates were evaporated in a rotary evaporator at 50°/20 mbar