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

HRID 2358357Notes

Reaction equation

HRID 2358357 reaction equation
CS(C)=O.C(Cl)(=O)C(Cl)=O.[OH:11][C@H:12]1[CH2:16][N:15]([C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:18])[C@H:14]([C:27]([O:29][CH3:30])=[O:28])[CH2:13]1.C(N(CC)C(C)C)(C)C>C(Cl)Cl.CCCCCC.CCOC(C)=O>[O:11]=[C:12]1[CH2:16][N:15]([C:17]([O:19][CH2:20][C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)=[O:18])[C@H:14]([C:27]([O:29][CH3:30])=[O:28])[CH2:13]1

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 6884112-Methyl 1-(phenylmethyl) (2S,4R)-4-hydroxy-1,2-pyrrolidinedicarboxylate

Product 1

HCID 115942881-Benzyl 2-methyl (2S)-4-oxopyrrolidine-1,2-dicarboxylateYield 70%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 21226206Ethyl acetate hexaneSolvent

Procedure

To solution of methyl sulfoxide (23.90 ml, 337 mmol) in DCM (100 ml) at −78° C. was added oxalyl chloride (2 M in DCM, 84 ml, 168 mmol) dropwise. The formed solution was stirred at this temperature for 30 min. A solution of (2S,4R)-1-benzyl 2-methyl 4-hydroxypyrrolidine-1,2-dicarboxylate (21.38 g, 77 mmol) in DCM (100 ml) was added dropwise at −78° C. The formed slurry was stirred at −78° C. for 2 hr before addition of N,N-Diisopropylethylamine (66.7 ml, 383 mmol) dropwise. The final solution was stirred at room temperature 3 h. The mixture was washed with iced 1M HCl, 5% citric acid, and then brine, dried over MgSO4, filtered, and evaporated. The residual light brown oil was purified by silica gel column chromatography, eluted with 4:1, 3:1, then 2:1 hexane-EtOAc to afford (S)-1-benzyl 2-methyl 4-oxopyrrolidine-1,2-dicarboxylate (14.8 g, 70% yield) as light brown viscous oil.

Workup

  1. washThe mixture was washed with iced 1M HCl, 5% citric acid
  2. dry with materialbrine, dried over MgSO4
  3. filtrationfiltered
  4. customevaporated
  5. customThe residual light brown oil was purified by silica gel column chromatography
  6. washeluted with 4:1, 3:1

Sources & evidence

ORD record
ord-c3e36d8e4001417eacb675af18b1a5a1
Source dataset
uspto-grants-2010_07
Patent number
US07763584B2

Reaction notes

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