tert-Butyl acetate → TERT-BUTYL (S)-4-(CBZ-AMINO)-5-METHYL-3-OXOHEXANOATE

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)

1. stirringThe resulting mixture was stirred for 2 h until the temperature
2. customrose to -15° C
3. customThe reaction was quenched with 400 ml saturated aqueous NH4Cl
4. extractionextracted with ether (3×200 ml)
5. washThe combined organic extracts were washed with 2N aqueous HCl (50 ml), saturated aqueous NaHCO3 (2×50 ml)
6. dry with materialdried over magnesium sulfate
7. customevaporated to dryness in vacuo
8. customThe residue was purified by column chromatography on silica gel

ORD record

ord-1a09c79c28e34a33bfdf04e86e126d18

Source dataset

uspto-grants-1999_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05939527