tert-butyl N-[(1S)-3-oxo-1-phenylpropyl]carbamate

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a dry, cooled (−78° C.) solution of ethyl (3S)-3-[(tert-butoxycarbonyl)amino]-3-phenylpropanoate from Step A (1.00 g, 3.41 mmol) was added a solution of DiBAl-H (6.82 mL, 6.82 mmol, 1 M in CH2Cl2) slowly over 30 min. After an additional 30 min of stirring at −78° C., the reaction was quenched by the rapid addition of saturated aqueous Rochelle's salt (32 mL). The cooling bath was then removed and the reaction was allowed to rapidly stir until a noticeable decrease in the amount of emulsion was observed. The layers were separated and the aqueous layer was extracted with CH2Cl2 (2×30 mL). Combined organics were dried over sodium sulfate, filtered and concentrated in vacuo to give an oil. This oil was purified by silica gel chromatography, eluting with a gradient of EtOAc:hexanes 5:95 to 40:60, to give the title compound. MS: m/z=150 (M−CO2C4H7). the reaction was quenched by the rapid addition of saturated aqueous Rochelle's salt (32 mL) The cooling bath was then removed to rapidly stir until a noticeable decrease in the amount of emulsion The layers were separated the aqueous layer was extracted with CH2Cl2 (2×30 mL) Combined organics were dried over sodium sulfate filtered concentrated in vacuo to give an oil This oil was purified by silica gel chromatography eluting with a gradient of EtOAc:hexanes 5:95 to 40:60

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

Procedure: To a solution of tert-butyl [(1S)-3-oxo-1-phenylpropyl]carbamate from Step B (0.820 g, 3.29 mmol) and methyl 1-aminocyclopentanecarboxylate hydrochloride (0.591 g, 3.29 mmol) in chloroform (33 mL) was added Hunig's base (0.574 mL, 3.29 mmol). After stirring at ambient temperature for 20 min, NaHB(OAc)3 (1.74 g, 8.22 mmol) was added as a solid. Upon completion of the reaction, saturated aqueous NaHCO3 (3 mL) was added and the mixture was allowed to stir for at least 2 h. Water (5 mL) and additional saturated NaHCO3 (3 mL) was then added to form two layers. The aqueous layer was extracted once with chloroform (50 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to give an oil. This oil was purified by silica gel chromatography, eluting with a gradient of MeOH:DCM 1:99 to 6:94, to give the title compound. MS: m/z=377 (M+1). was added to stir for at least 2 h to form two layers The aqueous layer was extracted once with chloroform (50 mL) The combined organic layers were dried over sodium sulfate filtered concentrated in vacuo to give an oil This oil was purified by silica gel chromatography eluting with a gradient of MeOH:DCM 1:99 to 6:94

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a dry, cooled (−78° C.) solution of ethyl (3S)-3-[(tert-butoxycarbonyl)amino]-3-phenylpropanoate from Step A (1.00 g, 3.41 mmol) was added a solution of DiBAl—H (6.82 mL, 6.82 mmol, 1 M in CH2Cl2) slowly over 30 min. After an additional 30 min of stirring at −78° C., the reaction was quenched by the rapid addition of saturated aqueous Rochelle's salt (32 mL). The cooling bath was then removed and the reaction was allowed to rapidly stir until a noticeable decrease in the amount of emulsion was observed. The layers were separated and the aqueous layer was extracted with CH2Cl2 (2×30 mL). Combined organics were dried over sodium sulfate, filtered and concentrated in vacuo to give an oil. This oil was purified by silica gel chromatography, eluting with a gradient of EtOAc:hexanes 5:95 to 40:60, to give the title compound. MS: m/z=150 (M−CO2C4H7). the reaction was quenched by the rapid addition of saturated aqueous Rochelle's salt (32 mL) The cooling bath was then removed to rapidly stir until a noticeable decrease in the amount of emulsion The layers were separated the aqueous layer was extracted with CH2Cl2 (2×30 mL) Combined organics were dried over sodium sulfate filtered concentrated in vacuo to give an oil This oil was purified by silica gel chromatography eluting with a gradient of EtOAc:hexanes 5:95 to 40:60

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

Procedure: To a solution of tert-butyl [(1S)-3-oxo-1-phenylpropyl]carbamate from Step B (0.820 g, 3.29 mmol) and methyl 1-aminocyclopentanecarboxylate hydrochloride (0.591 g, 3.29 mmol) in chloroform (33 mL) was added Hunig's base (0.574 mL, 3.29 mmol). After stirring at ambient temperature for 20 min, NaHB(OAc)3 (1.74 g, 8.22 mmol) was added as a solid. Upon completion of the reaction, saturated aqueous NaHCO3 (3 mL) was added and the mixture was allowed to stir for at least 2 h. Water (5 mL) and additional saturated NaHCO3 (3 mL) was then added to form two layers. The aqueous layer was extracted once with chloroform (50 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to give an oil. This oil was purified by silica gel chromatography, eluting with a gradient of MeOH:DCM 1:99 to 6:94, to give the title compound. MS: nm/z=377 (M+1). was added to stir for at least 2 h to form two layers The aqueous layer was extracted once with chloroform (50 mL) The combined organic layers were dried over sodium sulfate filtered concentrated in vacuo to give an oil This oil was purified by silica gel chromatography eluting with a gradient of MeOH:DCM 1:99 to 6:94

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

Procedure: To a solution of tert-butyl [(1S)-3-oxo-1-phenylpropyl]carbamate from Step B (0.820 g, 3.29 mmol) and methyl 1-aminocyclopentanecarboxylate hydrochloride (0.591 g, 3.29 mmol) in chloroform (33 mL) was added Hunig's base (0.574 mL, 3.29 mmol). After stirring at ambient temperature for 20 min, NaHB(OAc)3 (1.74 g, 8.22 mmol) was added as a solid. Upon completion of the reaction, saturated aqueous NaHCO3 (3 mL) was added and the mixture was allowed to stir for at least 2 h. Water (5 mL) and additional saturated NaHCO3 (3 mL) was then added to form two layers. The aqueous layer was extracted once with chloroform (50 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to give an oil. This oil was purified by silica gel chromatography, eluting with a gradient of MeOH:DCM 1:99 to 6:94, to give the title compound. MS: m/z=377 (M+1). was added to stir for at least 2 h to form two layers The aqueous layer was extracted once with chloroform (50 mL) The combined organic layers were dried over sodium sulfate filtered concentrated in vacuo to give an oil This oil was purified by silica gel chromatography eluting with a gradient of MeOH:DCM 1:99 to 6:94

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a dry, cooled (−78° C.) solution of ethyl (3S)-3-[(tert-butoxycarbonyl)amino]-3-phenylpropanoate from Step A (1.00 g, 3.41 mmol) was added a solution of DiBAl—H (6.82 mL, 6.82 mmol, 1 M in CH2Cl2) slowly over 30 min. After an additional 30 min of stirring at −78° C., the reaction was quenched by the rapid addition of saturated aqueous Rochelle's salt (32 mL). The cooling bath was then removed and the reaction was allowed to rapidly stir until a noticeable decrease in the amount of emulsion was observed. The layers were separated and the aqueous layer was extracted with CH2Cl2 (2×30 mL). Combined organics were dried over sodium sulfate, filtered and concentrated in vacuo to give an oil. This oil was purified by silica gel chromatography, eluting with a gradient of EtOAc:hexanes 5:95 to 40:60, to give the title compound. MS: m/z=150 (M−CO2C4H7). the reaction was quenched by the rapid addition of saturated aqueous Rochelle's salt (32 mL) The cooling bath was then removed to rapidly stir until a noticeable decrease in the amount of emulsion The layers were separated the aqueous layer was extracted with CH2Cl2 (2×30 mL) Combined organics were dried over sodium sulfate filtered concentrated in vacuo to give an oil This oil was purified by silica gel chromatography eluting with a gradient of EtOAc:hexanes 5:95 to 40:60