反应详情

温度

-78 °C

To a solution of LDA (1.8M in THF, 3.04 mL, 5.47 mmol,) and THF (40 mL) at about −78° C. was added ethyl 4-(dibenzylamino)-2-ethylcyclopentanecarboxylate (1.0 g, 2.7 mmol, Preparation #EE.1) in THF (4 mL). The reaction mixture was stirred at about −78° C. for about 1 h. MeI (2.57 mL, 41.0 mmol) was added and reaction mixture was stirred at about −78° C. for about 1 h and was then warmed to about −40° C. DCM (150 mL) was added followed by saturated aqueous NH4Cl solution (50 mL). The layers were separated and the aqueous layer was extracted with DCM (2×30 mL). The combined organic layers were washed with brine, dried over anhydrous MgSO4, filtered, and concentrated to dryness under reduced pressure. The residue was purified by flash silica gel chromatography eluting with a gradient of 0-10% EtOAc in DCM to give (2R,4S)-ethyl 4-(dibenzylamino)-2-ethyl-1-methylcyclopentanecarboxylate and (2S,4R)-ethyl 4-(dibenzylamino)-2-ethyl-1-methylcyclopentanecarboxylate (0.864 g, 84%). LC/MS (Table 2, Method a) Rt=2.25 min; MS m/z: 380 (M+H)+.

1. customreaction mixture
2. stirringwas stirred at about −78° C. for about 1 h
3. temperaturewas then warmed to about −40° C
4. customThe layers were separated
5. extractionthe aqueous layer was extracted with DCM (2×30 mL)
6. washThe combined organic layers were washed with brine
7. dry with materialdried over anhydrous MgSO4
8. filtrationfiltered
9. concentrationconcentrated to dryness under reduced pressure
10. customThe residue was purified by flash silica gel chromatography
11. washeluting with a gradient of 0-10% EtOAc in DCM