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

HRID 590663Notes

Reaction equation

HRID 590663 reaction equation
N1C=CC=CC=1.[OH:7][C@H:8]1[CH2:12][N:11]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C@H:10]([C:20]([O:22][CH3:23])=[O:21])[CH2:9]1>C(Cl)Cl>[O:7]=[C:8]1[CH2:12][N:11]([C:13]([O:15][C:16]([CH3:17])([CH3:18])[CH3:19])=[O:14])[C@H:10]([C:20]([O:22][CH3:23])=[O:21])[CH2:9]1

Participants

4

Reactant 2

HCID 1049PyridineHCID 2734883(2S,4R)-4-Hydroxypyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester

Product 1

HCID 109884851-tert-butyl 2-methyl (2S)-4-oxopyrrolidine-1,2-dicarboxylateYield 81.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

CrO3 (194 g, 1.94 mol) was added slowly with stirring over 30 min to a solution of pyridine (340 mL) in DCM (900 mL) at 0° C. The mixture was warmed to rt and (2S,4R)-1-tert-butyl 2-methyl 4-hydroxypyrrolidine-1,2-dicarboxylate (56 g, 0.216 mol) in DCM (700 mL) was added. The reaction was stirred vigorously for 4 hs at rt. The formed dark solid was decanted and washed with DCM. The organic phases were washed with aq. NaHCO3, 10% aqueous critic acid, and brine, and dried over anhydrous Na2SO4. The solvent was removed in vacuo and purified by silica gel column chromatography (PE: EtOAc=50:1 to 10:1) to afford (S)-1-tert-butyl 2-methyl 4-oxopyrrolidine-1,2-dicarboxylate (42.6 g, 81%) as yellow oil.

Workup

  1. customThe formed dark solid was decanted
  2. washwashed with DCM
  3. washThe organic phases were washed with aq. NaHCO3, 10% aqueous critic acid, and brine
  4. dry with materialdried over anhydrous Na2SO4
  5. customThe solvent was removed in vacuo
  6. custompurified by silica gel column chromatography (PE: EtOAc=50:1 to 10:1)

Sources & evidence

ORD record
ord-0cae69afad364ca6bd372d2d4fe13eae
Source dataset
uspto-grants-2016_01
Patent number
US09233974B2

Reaction notes

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