反应详情

温度

0 °C

A three necked round bottom flask fitted with a magnetic stir bar, nitrogen inlet, temperature probe and addition funnel was charged with sodium hydride (2 equiv.) and DMF. The mixture was cooled to 0° C., and a solution of methyl 1H-indol-3-ylacetate (2 equiv.) from Step 5 in DMF (1 M) was added dropwise. After the addition, the reaction was stirred for 15 min, upon which a DMF (0.5 M) solution of (2R)-2-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-1-[(4-fluorophenyl)sulfonyl]aziridine (1 equiv.) from Step 4 was added dropwise. The reaction was allowed to stir 1.5 h. Methyl iodide (5 equiv.) was then added to the reaction and stirred an additional 1 h. Aqueous 2M HCl (7.2 equiv.) was then added carefully to the reaction followed by an equal volume of EtOAc and stirring continued for 2 h. The solution was diluted with EtOAc and layers separated. The organic phase was washed with ½ saturated brine (2×), dried over Na2SO4, filtered and concentrated to an orange syrup. The syrup was diluted with MTBE upon which solid started to form. The suspension was vigorously stirred while additional MTBE was added dropwise over 15 min. The suspension was cooled to 0° C. and Heptanes was added dropwise. The reaction was stirred for 1 h, and filtered. The solid cake was washed with MTBE/Heptanes (2:1) and dried on the fit under nitrogen for 16 h to provide the title compound (75%) as a white solid.

1. customA three necked round bottom flask fitted with a magnetic stir bar, nitrogen inlet
2. additiontemperature probe and addition funnel
3. additionAfter the addition
4. additionwas added dropwise
5. stirringstirred an additional 1 h
6. stirringstirring
7. waitcontinued for 2 h
8. customseparated
9. washThe organic phase was washed with ½ saturated brine (2×)
10. dry with materialdried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated to an orange syrup
13. additionThe syrup was diluted with MTBE upon which solid
14. customto form
15. additionwas added dropwise over 15 min
16. temperatureThe suspension was cooled to 0° C.
17. stirringThe reaction was stirred for 1 h
18. filtrationfiltered
19. washThe solid cake was washed with MTBE/Heptanes (2:1)
20. customdried on the fit under nitrogen for 16 h