Acetic Acid → Methyl (2S,4R)-1-(tert-butoxycarbonyl)-4-methylpyroglutamate

Temperature

-78 °C

This compound is prepared as described by Gu et al, Tetrahedron Lett., 2003, 44, 3203-3205. Lithium hexamethyldisilazide in THF (1.0 M; 8.47 mL, 8.47 mmol) was added dropwise over 30 min. to a solution of 1-tert-butyl 2-methyl (2S)-5-oxopyrrolidine-1,2-dicarboxylate (2.0 g, 8.2 mmol) in THF (20 mL) at −78° C. The resulting mixture was stirred at −78° C. for 1 h. Methyl iodide (1.30 mL, 20.9 mmol) was then added dropwise over 10 min. After stirring at −78° C. for 2 h, the reaction mixture was allowed to warm to room temperature and stirred for 14 h. The reaction was then quenched with AcOH (1.00 mL, 17.6 mmol), and the reaction mixture was concentrated under reduced pressure. The residue was diluted with EtOAc (100 mL), washed with brine (100 mL), dried over Na2SO4, and concentrated under reduced pressure. The resulting residue was purified by flash chromatography on silica gel (0-50% EtOAc in hexanes) to give the sub-title compound (0.47 g, 22%). LCMS calc. for C12H19NNaO5 (M+Na)+: m/z=280.1. found 280.1. 1H NMR (CDCl3, 400 MHz) δ 4.57 (1H, dd, J=1.6 and 9.6 Hz), 3.77 (3H, s), 2.68 (1H, m), 2.27 (1H, m), 1.93 (1H, m), 1.49 (9H, s), 1.21 (3H, d, J=6.8 Hz) ppm.

1. customThis compound is prepared
2. stirringAfter stirring at −78° C. for 2 h
3. temperatureto warm to room temperature
4. stirringstirred for 14 h
5. concentrationthe reaction mixture was concentrated under reduced pressure
6. additionThe residue was diluted with EtOAc (100 mL)
7. washwashed with brine (100 mL)
8. dry with materialdried over Na2SO4
9. concentrationconcentrated under reduced pressure
10. customThe resulting residue was purified by flash chromatography on silica gel (0-50% EtOAc in hexanes)

ORD record

ord-4a7f2e625f9e4508b32c9c4f6a847df6

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09278950B2