反应详情

温度

-78 °C

In an oven-dried flask under an atmosphere of nitrogen, 1.1 g LiOH.H2O (26.25 mmol) in DMF (20 mL) was added to a stirring suspension of 4 angstrom molecular sieves. After 30 minutes of stirring at room temperature 2.8 mL (25 mmol) indoline was added dropwise. After one hour at room temperature 2.9 mL (26.25 mmol) Ethyl bromoacetate was added dropwise. After 1.5 h the solid material was filtered and the residue was washed with copious amounts of EtOAc. The organics were washed 3 times with water and the organic material was dried over MgSO4. The solvents were evaporated under reduced pressure. The crude material was then dissolved in 75 mL anhydrous THF, charged into an oven dried round bottom under an atmosphere of nitrogen, cooled to −78° C., and then treated with 26.25 mL a 1M solution of NaHMDS. The solution was allowed to stir for 30 minutes at −78° C. after which the enolate was quenched with 5.4 g (26.25 mmol) of parachlorobenzyl bromide (solution in 25 mL anhydrous THF). The reaction was allowed to warm to room temperature overnight. The next day the reaction was quenched with water. The aqueous layer was extracted with 3 large portions of EtOAc. The combined organics were dried over MgSO4. The solvents were removed under reduced pressure and the residue was purified by flash chromatography which yielded the title compound as a yellow oil. LC/MS m/e=331 (M+1). TLC Rf=0.22 (20:1 hexanes:EtOAc). 1H NMR (500 MHz, CDCl3): δ 1.11 (t, J=3.55 Hz, 3H), 2.96 (m, 2H), 3.06 (m, 1H), 3.25 (m, 1H), 3.60 (t, 2H), 4.07 (m, 2H), 4.36 (t, J=3.75 Hz, 1H).

1. additionwas added dropwise
2. filtrationAfter 1.5 h the solid material was filtered
3. washthe residue was washed with copious amounts of EtOAc
4. washThe organics were washed 3 times with water
5. dry with materialthe organic material was dried over MgSO4
6. customThe solvents were evaporated under reduced pressure
7. dissolutionThe crude material was then dissolved in 75 mL anhydrous THF
8. additioncharged into an oven
9. customdried round bottom under an atmosphere of nitrogen
10. additiontreated with 26.25 mL a 1M solution of NaHMDS
11. temperatureto warm to room temperature overnight
12. customThe next day the reaction was quenched with water
13. extractionThe aqueous layer was extracted with 3 large portions of EtOAc
14. dry with materialThe combined organics were dried over MgSO4
15. customThe solvents were removed under reduced pressure
16. customthe residue was purified by flash chromatography which