Sodium Cyanide → 1-tert-Butyl 2-methyl (2S,4R)-4-cyanopyrrolidine-1,2-dicarboxylate

HRID 399534Notes

Reaction equation

HRID 399534 reaction equation
[CH3:1][O:2][C:3](=[O:21])[C@@H:4]1[CH2:8][C@@H:7](OS(C)(=O)=O)[CH2:6][N:5]1[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15].[C-:22]#[N:23].[Na+]>CS(C)=O.C(OCC)(=O)C>[CH3:1][O:2][C:3](=[O:21])[C@@H:4]1[CH2:8][C@@H:7]([C:22]#[N:23])[CH2:6][N:5]1[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15]

Participants

5

Reactant 2

HCID 8929Sodium CyanideHCID 147726821-tert-Butyl 2-methyl (2S,4R)-4-((methanesulfonyl)oxy)pyrrolidine-1,2-dicarboxylate

Product 1

HCID 179989661-tert-Butyl 2-methyl (2S,4R)-4-cyanopyrrolidine-1,2-dicarboxylate

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
55 °C

Procedure

A mixture of (4R)-1-(tert-butyloxycarbonyl)-4-(methane-sulfonyloxy)-L-proline methyl ester (2.31 g, 7.14 mmol) and sodium cyanide (3.5 g, 71.4 mmol) in dry dimethylsulfoxide (46 mL) was stirred for 24 hours at 55° C. under a nitrogen atmosphere. The cooled reaction mixture was diluted with ethyl acetate, washed with water (2×), saturated brine solution, dried (MgSO4), and evaporated. The crude product mixture was subjected to flash silica gel chromatography eluting with 15% acetone/hexane. Fractions containing the desired nitrile were combined and evaporated to afford a colorless oil; yield 205 mg (11%).

Workup

  1. customThe cooled reaction mixture
  2. washwashed with water (2×), saturated brine solution
  3. dry with materialdried (MgSO4)
  4. customevaporated
  5. washeluting with 15% acetone/hexane
  6. additionFractions containing the desired nitrile
  7. customevaporated
  8. customto afford a colorless oil

Sources & evidence

ORD record
ord-1febc6432f9844c2a30ce34c6928f65a
Source dataset
uspto-grants-1998_10
Patent number
US05821261

Reaction notes

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