3-Cyanopyridine → (S)-3-oxiranylpyrrolidine-1-carboxylic acid t-butyl ester

HRID 533376Notes

Reaction equation

HRID 533376 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([CH:13]=[CH2:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].N1C=CC=C(C#N)C=1.[OH:23]O>C[Re](=O)(=O)=O>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([CH:13]2[CH2:14][O:23]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 793-CyanopyridineHCID 784Hydrogen PeroxideHCID 46222798(R)-tert-Butyl 3-vinylpyrrolidine-1-carboxylate

Product 1

HCID 86650332(S)-3-oxiranylpyrrolidine-1-carboxylic acid t-butyl esterYield 63.9%

Reagents, catalysts & solvents 1

HCID 178477782HCID 178477782, compoundCatalyst2×

Procedure

To (R)-3-vinylpyrrolidine-1-carboxylic acid t-butyl ester (6.1 g, 30.8 mmol) was added 3-pyridinecarbonitrile (320 mg, 3.1 mmol) and methyltrioxorhenium(VII) (192 mg, 769 μmol). The mixture was stirred until homogeneous. The mixture was placed in an ice water bath and 30% hydrogen peroxide (33:77, hydrogen peroxide:H2O, 4.08 mL, 40.0 mmol) was added, while keeping the temperature below 35° C. The mixture was stirred for 2 hours. Additional methyltrioxorhenium(VII) (50 mg) was added and the mixture was stirred for 2 hours. The organic layer was collected and washed with a saturated sodium metabisulfite solution (10 mL) under an ice bath. The material was then washed with saturated aqueous NaCl. The organic layer was collected, dried over Na2SO4, filtered, and concentrated. The crude product was purified by column chromatography (0-100% EtOAc in hexanes) to give (S)-3-oxiranylpyrrolidine-1-carboxylic acid t-butyl ester as a yellowish oil (4.2 g).

Workup

  1. customThe mixture was placed in an ice water bath
  2. customthe temperature below 35° C
  3. stirringThe mixture was stirred for 2 hours
  4. stirringthe mixture was stirred for 2 hours
  5. customThe organic layer was collected
  6. washwashed with a saturated sodium metabisulfite solution (10 mL) under an ice bath
  7. washThe material was then washed with saturated aqueous NaCl
  8. customThe organic layer was collected
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe crude product was purified by column chromatography (0-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-f974cbea63b348529ac8b21a02bcc5c9
Source dataset
uspto-grants-2014_10
Patent number
US08853255B2

Reaction notes

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