反应详情

To a solution of N-CBZ L-aspartic acid 1-methyl ester (1.00 g, 3.55 mmol) in dry tetrahydrofuran (17 mL) is added carbonyl diimidazole (634.1 mg, 3.91 mmol). The mixture is stirred at room temperature for 6 hr then the magnesium salt of mono-tert butyl malonate (1.339 g, 3.91 mmol) (prepared according to Angew. Chem. Int. Ed. Engl. 1979, 18(1), 72-74) is added. The mixture is stirred at room temperature for another 20 h, then concentrated in vacuum. The residue is partitioned between ether (60 mL) and 0.5 N HCl (60 mL). The organic layer is washed with saturated NaHCO3 solution (50 mL) then dried over magnesium sulfate and concentrated in vacuum. The residue is purified over 35 g of silica gel, eluted with EtOAc:Heptane (1:1) to afford (S)-2-Benzyloxycarbonylamino-4-oxo-hexanedioic acid 6-tert-butyl ester 1-methyl ester (1.17 g, 87%).

1. stirringThe mixture is stirred at room temperature for another 20 h
2. concentrationconcentrated in vacuum
3. customThe residue is partitioned between ether (60 mL) and 0.5 N HCl (60 mL)
4. washThe organic layer is washed with saturated NaHCO3 solution (50 mL)
5. dry with materialthen dried over magnesium sulfate
6. concentrationconcentrated in vacuum
7. customThe residue is purified over 35 g of silica gel
8. washeluted with EtOAc:Heptane (1:1)