Sodium hydride → tert-butyl (2S)-2-(oxiran-2-yl)pyrrolidine-1-carboxylate

HRID 1720527Notes

Reaction equation

HRID 1720527 reaction equation
[H-].[Na+].[I-].[CH3:4][S+](C)C.[C:8]([O:12][C:13]([N:15]1[CH2:21][CH2:20][CH2:19][C@H:16]1[CH:17]=[O:18])=[O:14])([CH3:11])([CH3:10])[CH3:9]>CS(C)=O.C1COCC1>[C:8]([O:12][C:13]([N:15]1[CH2:21][CH2:20][CH2:19][C@H:16]1[CH:17]1[O:18][CH2:4]1)=[O:14])([CH3:11])([CH3:9])[CH3:10]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 75127Trimethylsulfonium iodideHCID 2734674tert-butyl (2S)-2-formylpyrrolidine-1-carboxylate

Product 1

HCID 15297813tert-butyl (2S)-2-(oxiran-2-yl)pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
70 °C

Procedure

DMSO (20 ml) was added to sodium hydride (1.55 g, NaH content 60%), and the mixture was stirred at 70° C. for 1 hour. The reaction mixture was cooled to room temperature and THF (20 ml) was added. The mixture was cooled to -5° C., and thereto was dropwise added a solution of trimethylsulfonium iodide (7.90 g) in DMSO (30 ml) over 3 minutes. After stirring for 1 minute, a solution of tert-butoxycarbonyl-L-prolinal (5.13 g) in THF (15 ml) was added quickly, followed by stirring at room temperature for 1 hour. The reaction mixture was poured into ice-water (300 ml), and extracted with chloroform. The extract was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography (eluate: hexane-ethyl acetate) to give two diastereomers of the title compound, 3.12 g of its less polar compound and 1.28 g of its more polar compound. (Configuration of the epoxy moiety of the both has not been identified.) The less polar compound was used in the following reactions.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. temperatureThe mixture was cooled to -5° C.
  3. stirringAfter stirring for 1 minute
  4. stirringby stirring at room temperature for 1 hour
  5. extractionextracted with chloroform
  6. washThe extract was washed with saturated brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel column chromatography (eluate: hexane-ethyl acetate)

Sources & evidence

ORD record
ord-798368a7eaed46879a4fd3ff438ef6fd
Source dataset
uspto-grants-1996_04
Patent number
US05506256

Reaction notes

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