(S)-tert-butyl 2-(bis(tert-butoxycarbonyl)amino)-5-oxopentanoate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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)+. at −78° C. The resulting reaction mixture Then, the reaction was quenched with saturated aqueous NH4Cl (0.5 mL) solution by removing the external acetone/dry ice bath The reaction solution was diluted with ethyl acetate (20 mL) an aqueous saturated solution of NH4Cl (15 mL) was added with stirring The aqueous phase was extracted with ethyl acetate (50 mL) the combined organic layers dried concentrated under reduced pressure The resulting residue was purified on 12 g silica gel column (eluent, hexanes to 40% ethyl acetate in hexanes)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of (S)-1-tert-butyl 5-ethyl 2-(bis(tert-butoxycarbonyl)amino)pentanedioate (1.7 g, 3.93 mmol) in dry tetrahydrofuran (30 mL) was cooled to −78° C. with acetone/dry ice bath and added diisobutylaluminum hydride (1.0 M in hexanes 5.9 mL, 5.90 mmol) dropwise over the period of 5 minutes. The reaction was complete after stirring for four hours, then quenched with water (1.5 mL) and allowed to warm to room temperature by removing the external cold bath. The resulting white thick solution was filtered through celite powder and washed with diethyl ether (200 mL). The filtrate was concentrated under reduced pressure and purified on 40 g silica gel column (eluent hexanes to 20% ethyl acetate in hexanes) to afford (S)-tert-butyl 2-(bis(tert-butoxycarbonyl)amino)-5-oxopentanoate (0.90 g, 59.1% yield) as a thick oil. 1H NMR (CDCl3) δ ppm: 9.79 (s, 1H), 4.77 (dd, J=9.3, 5.2 Hz, 1H), 2.52 (m, 3H), 2.16 (m, 1H), 1.52 (s, 18H), 1.47 (s, 9H). 13C NMR (CDCl3) δ ppm: 201.2, 169.2, 152.4, 83.1, 81.5, 58.11, 40.7, 28.0, 27.9 and 21.9. MS (ESI+): 410 (M+Na)+. quenched with water (1.5 mL) by removing the external cold bath The resulting white thick solution was filtered through celite powder washed with diethyl ether (200 mL) The filtrate was concentrated under reduced pressure purified on 40 g silica gel column (eluent hexanes to 20% ethyl acetate in hexanes)