1,1'-Carbonyldiimidazole → (S)-2-Benzyloxycarbonylamino-4-oxo-hexanedioic acid 6-tert-butyl ester 1-methyl ester

Temperature

25 °C

In a flask under argon was placed (S)-2-benzyloxycarbonylamino-succinic acid 1-methyl ester (3.0 g, 10.67 mmol) and tetrahydrofuran (50 mL). To this mixture was added carbonyldiimidazole (1.90 g, 11.74 mmol) and the resulting mixture was stirred at 25° C. for 6 h. In a separate round bottom flask was placed malonic acid mono t-butyl ester (1.98 g, 11.74 mmol), tetrahydrofuran (30 mL) and magnesium ethoxide (685 mg, 5.87 mmol) and the resulting mixture stirred at 25° C. for 1 h and then concentrated in vacuo. The residue was taken up in tetrahydrofuran (15 mL) and added to the flask containing the succinic acid and carbonyldiimidazole mixture and stirred at 25° C. for 16 h. The mixture was concentrated in vacuo and partitioned between diethyl ether (200 mL) and a 0.5N aqueous hydrochloric acid solution (200 mL). The organic layer was washed with a saturated aqueous sodium bicarbonate solution (150 mL), dried over sodium sulfate and concentrated. Purification by flash column chromatography (silica gel 60, 230-400 mesh; 40% ethyl acetate/hexanes) afforded (S)-2-benzyloxycarbonylamino-4-oxo-hexanedioic acid 6-t-butyl ester 1-methyl ester (3.04 g, 75%) as a pale yellow oil.

1. customIn a flask under argon was placed
2. customIn a separate round bottom flask was placed
3. concentrationconcentrated in vacuo
4. additionadded to the flask
5. additioncontaining the succinic acid and carbonyldiimidazole mixture
6. stirringstirred at 25° C. for 16 h
7. concentrationThe mixture was concentrated in vacuo
8. custompartitioned between diethyl ether (200 mL)
9. washThe organic layer was washed with a saturated aqueous sodium bicarbonate solution (150 mL)
10. dry with materialdried over sodium sulfate
11. concentrationconcentrated
12. customPurification by flash column chromatography (silica gel 60, 230-400 mesh; 40% ethyl acetate/hexanes)

ORD record

ord-df18b23ab4b4405da9bf1297fdc88c42

Source dataset

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07741327B2