Pyridine → tert-butyl (2S)-2-cyanopyrrolidine-1-carboxylate

HRID 1350242Notes

Reaction equation

HRID 1350242 reaction equation
C(Cl)(=O)C(Cl)=O.CN(C=O)C.[C:12]([NH:19]C(=O)[C@@H]1CCCN1)([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13].[N:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>CC#N.CCOC(C)=O>[C:32]([C@@H:31]1[CH2:30][CH2:29][CH2:28][N:19]1[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])#[N:27]

Participants

7

Reactant 4

HCID 1049PyridineHCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 57475027N-boc-proline amide

Product 1

HCID 6951263tert-butyl (2S)-2-cyanopyrrolidine-1-carboxylateYield 66%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of oxalyl chloride (11.0 ml, 0.126 mol) and DMF (11.4 ml, 0.138 mol) in MeCN (170 ml) was treated dropwise with a solution of N-Boc-L-proline amide (12.3 g, 0.57 mol) and pyridine (20.4 ml, 0.253 mol) in MeCN (30 ml) at 0° C. and stirred at this temperature for 15 minutes. The reaction mixture was diluted with EtOAc and washed with H2O (×3). The organic extract was dried over anhydrous MgSO4 and filtered. The solvent was removed under reduced pressure. The residue was purified on a silica column eluting with a solvent gradient of pentane:EtOAc (80:20) gradually changing to (60:40) to afford the title compound (7.40 g, 66%).

Workup

  1. washwashed with H2O (×3)
  2. extractionThe organic extract
  3. dry with materialwas dried over anhydrous MgSO4
  4. filtrationfiltered
  5. customThe solvent was removed under reduced pressure
  6. customThe residue was purified on a silica column
  7. washeluting with a solvent gradient of pentane:EtOAc (80:20)

Sources & evidence

ORD record
ord-6baf98fcde6d4ecaad08b8f9c078904f
Source dataset
uspto-grants-2007_05
Patent number
US07214694B2

Reaction notes

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