反应详情

To a solution of tert-butyl propiolate (42.7 mg, 0.34 mmol) in a dry THF (1.5 mL) was slowly added lithium diisopropylamide (2.0 M in THF/ethyl benzene, 0.15 mL, 0.29 mmol) at −78° C. under nitrogen atmosphere. The resulting reaction mixture was continued stirring at the same temperature for 1.0 hour (to generate lithium propiolate anion), then slowly added (S)-tert-butyl 2-(bis(tert-butoxycarbonyl)amino)-5-oxopentanoate (0.075 g, 0.193 mmol) in 1.0 mL THF solution. The mixture was stirred at the same temperature for 90 minutes (until finished by TLC). Then, the reaction was quenched with saturated aqueous NH4Cl (0.5 mL) solution and warmed to room temperature by removing the external acetone/dry ice bath. The reaction solution was diluted with ethyl acetate (20 mL) and an aqueous saturated solution of NH4Cl (15 mL) was added with stirring. The aqueous phase was extracted with ethyl acetate (50 mL) and the combined organic layers dried and concentrated under reduced pressure. The resulting residue was purified on 12 g silica gel column (eluent, hexanes to 40% ethyl acetate in hexanes) to afford (7S)-di-tert-butyl 7-(bis(tert-butoxycarbonyl)amino)-4-hydroxyoct-2-ynedioate (diastereomeric mixture, 40 mg, 40.3% yield) as an oil. 1H NMR (CDCl3) δ ppm: 4.76 (dt, J=9.2, 5.2 Hz, 1H), 4.53 (m, 1H), 2.27 (m, 1H), 2.04 (m, 1H), 1.83 (m, 2H), 1.52 (s, 18H), 1.50 (s, 9H), 1.46 (s, 9H). 13C NMR (CDCl3) δ ppm: 169.63, 169.52, 152.47, 152.40, 152.34, 84.96, 84.94, 83.63, 83.09, 83.04, 81.48, 81.46, 77.89, 77.84, 61.90, 61.37, 58.47, 58.31, 33.75, 33.70, 28.02, 27.96, 27.93, 25.13 and 24.72. MS (ESI+): 536 (M+Na)+.

1. customat −78° C.
2. customThe resulting reaction mixture
3. customThen, the reaction was quenched with saturated aqueous NH4Cl (0.5 mL) solution
4. customby removing the external acetone/dry ice bath
5. additionThe reaction solution was diluted with ethyl acetate (20 mL)
6. additionan aqueous saturated solution of NH4Cl (15 mL) was added
7. stirringwith stirring
8. extractionThe aqueous phase was extracted with ethyl acetate (50 mL)
9. customthe combined organic layers dried
10. concentrationconcentrated under reduced pressure
11. customThe resulting residue was purified on 12 g silica gel column (eluent, hexanes to 40% ethyl acetate in hexanes)