tert-Butyl (S)-4-(Cbz-amino)-5-methyl-3-oxohexanoate

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of t-butyl-(4S)-4-(N-benzyloxycarbonylamino)-5-methyl-3-oxohexanoate (6.0 g, 17.1 mmol) in 70 ml ethanol at 0° C. was added potassium borohydride (3.23 g, 58.8 mmol). After stirring for 4 h at 0° C. and 12 h at room temperature, the reaction mixture was acidified with glacial acetic acid to pH 4 and concentrated in vacuo. The residue was dissolved in a mixture of 200 ml ethyl acetate and 200 ml water. After additional washings of the aqueous phase with ethyl acetate (3×50 ml), the combined organic extracts were dried over magnesium sulfate and concentrated in vacuo. The crude product was purified by column chromatography on silica gel using ethyl acetate-hexane (1:4) as eluent to give the alcohol as a white solid (5.31 g). concentrated in vacuo The residue was dissolved in a mixture of 200 ml ethyl acetate and 200 ml water After additional washings of the aqueous phase with ethyl acetate (3×50 ml), the combined organic extracts were dried over magnesium sulfate concentrated in vacuo The crude product was purified by column chromatography on silica gel

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

Procedure: To an ice-cooled solution of Z-Valine (5 g, 19.9 mmol) in 60 ml tetrahydrofuran was added N,N'-carbonyldiimidazole (3.55 g, 22.3 mmol) in one portion and the resulting mixture stirred for 3 h. t-Butyl acetate (13.5 ml, 100 mmol) was added dropwise to a solution of LDA (90 mmol in tetrahydrofuran (270 ml) at -78° C. After 30 min, the imidazolide solution was added dropwise via double-ended needle to the enolate. The resulting mixture was stirred for 2 h until the temperature rose to -15° C. The reaction was quenched with 400 ml saturated aqueous NH4Cl and extracted with ether (3×200 ml). The combined organic extracts were washed with 2N aqueous HCl (50 ml), saturated aqueous NaHCO3 (2×50 ml), dried over magnesium sulfate and evaporated to dryness in vacuo. The residue was purified by column chromatography on silica gel using ethyl acetate-hexane (1:4) as an eluent to give the product as a colorless oil (6.88 g). rose to -15° C The reaction was quenched with 400 ml saturated aqueous NH4Cl extracted with ether (3×200 ml) The combined organic extracts were washed with 2N aqueous HCl (50 ml), saturated aqueous NaHCO3 (2×50 ml) dried over magnesium sulfate evaporated to dryness in vacuo The residue was purified by column chromatography on silica gel

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

Procedure: To an ice-cooled solution of Z-valine (5 g, 19.9 mmol) in 60 ml tetrahydrofurane was added N,N'-cabonyldiimidazole (3.55 g, 22.3 mmol) in one portion and stirred for 3 h. At -78° C., tert-butyl acetate (13.5 ml, 100 mmol) was dropped to a solution of LDA (90 mmol) in tetrahydrofurane (270 ml). After 30', the imidazolide solution was added dropwise via double-ended needle to the enolate. The resulting mixture was stirred for 2 h until the temperature rose to -15° C. The reaction was quenched with 400 ml saturated aqueous NH4Cl and extracted with ether (3×200 ml). The combined organic extracts were washed with 2N aqueous HCl (50 ml), saturated aqueous NaHCO3 (2×50 ml), dried over magnesium sulfate and evaporated to dryness in vacuo. The residue was purified by column chromatography on silica gel using ethyl acetate-hexane (1:4) as an eluent to give the product as a colorless oil (6.88 g) The resulting mixture was stirred for 2 h until the temperature rose to -15° C The reaction was quenched with 400 ml saturated aqueous NH4Cl extracted with ether (3×200 ml) The combined organic extracts were washed with 2N aqueous HCl (50 ml), saturated aqueous NaHCO3 (2×50 ml) dried over magnesium sulfate evaporated to dryness in vacuo The residue was purified by column chromatography on silica gel