1,1'-Carbonyldiimidazole → (R)-ethyl 5-(benzyloxy)-4-((tert-butoxycarbonyl)amino)-3-oxopentanoate

To a 250-mL round-bottomed flask was added (R)-3-(benzyloxy)-2-((tert-butoxycarbonyl)amino)propanoic acid (5.68 g, 19.2 mmol) (Sigma-Aldrich), 1,1′-carbonyldiimidazole (4.68 g, 28.8 mmol), and THF (100 mL). The reaction mixture was stirred at RT for 4 h. The reaction mixture was treated with magnesium chloride (3.66 g, 38.4 mmol) (Strem Chem.) followed by ethyl potassium malonate (6.54 g, 38.4 mmol) (Sigma-Aldrich) and heated at 50° C. for 18 h. The solvents were removed under vacuum and the residue was dissolved EtOAc (200 mL), washed sequentially with 10% sodium bisulfate (10 mL), sat NaHCO3 (2×10 mL), brine, dried over Na2SO4, and concentrated. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g), eluted with a gradient of 0-30% EtOAc in hexanes, to provide the title compound (5.73 g, 82% yield) as a white solid. ee % was not determined m/z (ESI, +ve) 388.2 (M+Na)+.

1. temperatureheated at 50° C. for 18 h
2. customThe solvents were removed under vacuum
3. dissolutionthe residue was dissolved EtOAc (200 mL)
4. washwashed sequentially with 10% sodium bisulfate (10 mL)
5. dry with materialdried over Na2SO4
6. concentrationconcentrated
7. customThe crude material was absorbed onto a plug of silica gel
8. custompurified by chromatography through a Redi-Sep pre-packed silica gel column (40 g)
9. washeluted with a gradient of 0-30% EtOAc in hexanes

ORD record

ord-c85a492754c84b0eaf9e8b69da0efcec

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09394297B2