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

HRID 411749Notes

Reaction equation

HRID 411749 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[C:11]([N:18]1[CH2:26][CH:25]([OH:27])[CH2:24][C@H:19]1[C:20]([O:22][CH3:23])=[O:21])([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12]>C(Cl)Cl>[C:11]([N:18]1[CH2:26][C:25](=[O:27])[CH2:24][C@H:19]1[C:20]([O:22][CH3:23])=[O:21])([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12]

Participants

5

Reactant 3

HCID 679Dimethyl SulfoxideHCID 65578Oxalyl chlorideHCID 121855781-(tert-butyl) 2-methyl (2S)-4-hydroxypyrrolidine-1,2-dicarboxylate

Product 1

HCID 109884851-tert-butyl 2-methyl (2S)-4-oxopyrrolidine-1,2-dicarboxylateYield 81.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 3.5 mL (40.2 mmol) of oxalyl chloride in 20 mL of CH2Cl2 was cooled in a −78° C. bath and 3.5 mL (49.3 mmol) of dry DMSO was added. After 30 min, a solution of 5.31 g (23 mmol) of N-(BOC)-4-hydroxy-(L)-proline, methyl ester was added. A precipitate developed during the addition. After 30 min at −78° C., 15 mL (107 mmol) of TEA was added. Another 30 mL of CH2Cl2 was added to the reaction mixture to facilitate stirring and cold bath was removed. After 1.5 hr the solution was partitioned between CH2Cl2 and water. The organic layer was washed with water, 1.2 N HCl, brine then dried over anydrous Na2SO4. The filtrate was concentrated in vacuo and the residue was purified by flash column chromatography on silica gel eluted with a gradient of 20-40% EtOAc/hexane to yield N-(BOC)-4-oxo-(L)-proline, methyl ester (4.56 g).

Workup

  1. additionA precipitate developed during the addition
  2. waitAfter 30 min at −78° C.
  3. customcold bath was removed
  4. customAfter 1.5 hr the solution was partitioned between CH2Cl2 and water
  5. washThe organic layer was washed with water, 1.2 N HCl, brine
  6. dry with materialthen dried over anydrous Na2SO4
  7. concentrationThe filtrate was concentrated in vacuo
  8. customthe residue was purified by flash column chromatography on silica gel
  9. washeluted with a gradient of 20-40% EtOAc/hexane

Sources & evidence

ORD record
ord-38f0679520594e8eaf4db0b89236b21b
Source dataset
uspto-grants-2003_05
Patent number
US06559174B2

Reaction notes

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