1,1'-Carbonyldiimidazole → Ethyl 4-((tert-butoxycarbonyl)amino)-4-methyl-3-oxopentanoate

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Reaction Steps

To a 1-liter, 3 neck, round-bottomed flask equipped with a mechanical stirrer and internal temperature probe was added Boc-Aib-OH (Bachem) (20 g, 98 mmol) and THF (500 mL). To the mixture at RT was added 1,1′-carbonyldiimidazole (Sigma-Aldrich) (23.9 g, 148 mmol) in portions. The solution was stirred for 2.5 h at RT. To the solution was added magnesium chloride (18.7 g, 197 mmol) and ethyl potassium malonate (Sigma-Aldrich) (33.5 g, 197 mmol). The solution was stirred at 50° C. for 17 h and then the solution was cooled to RT. The solution was diluted with EtOAc (400 mL) and filtered and the filter cake was washed with EtOAc. The filtrate was concentrated and the resulting material was diluted with EtOAc and hexanes. The solution was filtered and the filtrate was concentrated onto silica. Purification by silica gel chromatography (0-20% EtOAc/hexanes) afforded the title compound as a white solid (4.65 g, 17.0 mmol, 17% yield). m/z (ESI, +ve ion) 296.1 (M+Na)+.

Provenance & Evidence