反应详情

温度

85 °C

To a solution of (S)-2-[tert-Butoxycarbonyl-(2-methoxycarbonyl-ethyl)-amino]-succinic acid 4-methyl ester (intermediate 12, 420 g, 1.35 mol) in THF (2 L) under nitrogen cooled to 0° C. was added NaOMe/MeOH (1.5 L, 2.7M) in half an hour. The resulting yellow solution was stirred at 85° C. for 3 hours (after 1 hour a suspension was obtained). THF (1.5 L) was distilled off under the reduced pressure and water (2 L) was added. The resulting mixture was stirred at 110° C. for 20 hours. The mixture was washed with ethyl acetate (2×1 L). The aqueous solution was cooled to 0° C. and the value of pH was adjusted to 2.5 with concentrated HCl. The product was extracted with ethyl acetate (3×1 L) and the organic extracts were combined, washed with saturated NaCl (1 L), dried (Na2SO4) and filtered. The filtrate was cooled to 0° C. and tert-butylamine (145 ml, 1.35 mol) was added with stirring. The yellow solid was collected by filtration and dried, then boiled in isopropyl alcohol (1.5 L). The suspension was cooled to 5° C. and collected by filtration to give 180 g of intermediate 3 (light white solid, yield:45%).

1. customwas obtained)
2. distillationTHF (1.5 L) was distilled off under the reduced pressure and water (2 L)
3. additionwas added
4. stirringThe resulting mixture was stirred at 110° C. for 20 hours
5. washThe mixture was washed with ethyl acetate (2×1 L)
6. temperatureThe aqueous solution was cooled to 0° C.
7. extractionThe product was extracted with ethyl acetate (3×1 L)
8. washwashed with saturated NaCl (1 L)
9. dry with materialdried (Na2SO4)
10. filtrationfiltered
11. temperatureThe filtrate was cooled to 0° C.
12. stirringwith stirring
13. filtrationThe yellow solid was collected by filtration
14. customdried
15. temperatureThe suspension was cooled to 5° C.
16. filtrationcollected by filtration