Dimethyl Sulfoxide → 1-tert-butyl 2-methyl (2S)-4-oxopyrrolidine-1,2-dicarboxylate

Temperature

-78 °C

To a solution of 9.63 mL (7.2 mmol) of oxalyl chloride in 10.6 mL of CH2Cl2 stirred at −78° C. was added a solution of 0.94 mL (13.2 mmol) of methyl sulfoxide in 15 mL of CH2Cl2. The solution was stirred at −78° C. for 30 min. A solution of 1.47 g (6 mmol) of N-Boc-4-hydroxyproline methyl ester in 19 mL of CH2Cl2 was then added dropwise. The mixture was stirred at −78° C. for 1.5 h, and 3.34 mL (24 mmol) of triethylamine was added. The solution was allowed to warm up to room temperature and stirred overnight. It was then diluted with 100 mL of CH2Cl2, washed successively with 100 mL of water, 100 mL of 1N HCl, and 100 mL of brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography over silica gel (eluted with ethyl acetate/hexanes, 1:3), to afford 1.294 g (89% yield) of N-Boc-4-oxo-proline methyl ester. 1H NMR (500 MHz, CDCl3) δ 1.45 (m, 9H), 2.60 (m, 1H), 2.95 (m, 1H), 3.75 (m, 3H), 3.90 (m, 2H), 4.80 (m, 1H).

1. stirringThe mixture was stirred at −78° C. for 1.5 h
2. temperatureto warm up to room temperature
3. stirringstirred overnight
4. washwashed successively with 100 mL of water, 100 mL of 1N HCl, and 100 mL of brine
5. dry with materialdried (MgSO4)
6. concentrationconcentrated in vacuo
7. customThe residue was purified by column chromatography over silica gel (eluted with ethyl acetate/hexanes, 1:3)

ORD record

ord-3a6bc4d6c6fb4de0ba8f3845dbc56335

Source dataset

uspto-grants-2003_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06531474B1