Dimethyl Sulfoxide → 1-tert-Butyl 2-methyl 4-oxopyrrolidine-1,2-dicarboxylate

Temperature

0 °C

To a stirred solution of (2S, 4R)-4-hydroxyproline (Aldrich) (25 g, 108 mmol) in methanol (50 mL) at 0° C. was added trimethylsilyldiazomethene (24.6 g, 216 mmol). The mixture was stirred at 0° C. for 1 hour. The residue obtained on removal of solvent and purification by column chromatography using 50% ethyl acetate in hexanes (27 g, 100%) was used in the next step. To oxalyl chloride (15 g, 118 mmol) in DCM (15 mL) at −78° C., DMSO (18.6 mL, 236 mmol) was added slowly over 15 minutes. After the completion of addition, the above product (2S, 4R)-N-Boc-4-hydroxyproline methylester (26.5 g, 108 mmol) in DCM (100 mL) was added at −78° C. dropwise over 20 minutes. Triethylamine (54.6 g, 540 mmol) was added followed by stirring at room temperature for 2 hours. The reaction mixture was then washed with 10% aq HCl (200 mL) and the organic layer was separated and dried over sodium sulfate. The crude product obtained on removal of solvent was purified on silica gel column chromatography using 50% EtoAc in hexanes to obtain 4-oxo-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (20 g, 78%).

1. customThe residue obtained on removal of solvent and purification by column chromatography
2. additionAfter the completion of addition
3. stirringby stirring at room temperature for 2 hours
4. washThe reaction mixture was then washed with 10% aq HCl (200 mL)
5. customthe organic layer was separated
6. dry with materialdried over sodium sulfate
7. customThe crude product obtained on removal of solvent
8. customwas purified on silica gel column chromatography

ORD record

ord-f34011e744c4441e8b8f6f013d6b4995

Source dataset

uspto-grants-2007_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07199105B2