Trifluoroacetic acid → Ethyl 3-amino-4-cyanopyridine-2-carboxylate

HRID 1936701Notes

Reaction equation

HRID 1936701 reaction equation
[C:1]([CH:3]([NH:9][CH:10]=O)[C:4]([O:6][CH2:7][CH3:8])=[O:5])#[N:2].[C:12](#[N:15])[CH:13]=[CH2:14].FC(F)(F)C(O)=O>ClCCCl>[NH2:2][C:1]1[C:3]([C:4]([O:6][CH2:7][CH3:8])=[O:5])=[N:9][CH:10]=[CH:14][C:13]=1[C:12]#[N:15]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7855AcrylonitrileHCID 12562418Ethyl 2-cyano-2-formamidoacetate

Product 1

HCID 22462344Ethyl 3-amino-4-cyanopyridine-2-carboxylateYield 21%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A stirred solution of ethyl 2-cyano-2-(formylamino)acetate (J. Org. Chem., 1979, 44, 3835; 0.47 g, 0.003 mol), acrylonitrile (1.2 ml, 0.018 mol) and tri-fluoroacetic acid (0.02 ml, 0.0003 mol) in 1,2-dichloroethane (4 ml) was heated under reflux for 3 days. The solvent was removed by evaporation under vacuum, the residue dissolved in dichloromethane (30 ml) and the resulting solution washed with saturated aqueous sodium bicarbonate solution (30 ml). The aqueous phase was washed with dichloromethane (30 ml) and the organic solutions then combined, dried (MgSO4) and evaporated under vacuum. Chromatography of the residue on silica gel (12 g), eluting with dichloromethane:methanol (100:1), followed by crystallization from acetone:hexane, gave the title compound as a colourless solid (0.12 g, 21%), m.p. 114-116° C.

Workup

  1. temperatureunder reflux for 3 days
  2. customThe solvent was removed by evaporation under vacuum
  3. dissolutionthe residue dissolved in dichloromethane (30 ml)
  4. washthe resulting solution washed with saturated aqueous sodium bicarbonate solution (30 ml)
  5. washThe aqueous phase was washed with dichloromethane (30 ml)
  6. dry with materialdried (MgSO4)
  7. customevaporated under vacuum
  8. washChromatography of the residue on silica gel (12 g), eluting with dichloromethane:methanol (100:1)
  9. customfollowed by crystallization from acetone

Sources & evidence

ORD record
ord-b1dfdffaddcf4f9ba79ac9e9d54bf0a5
Source dataset
uspto-grants-2002_05
Patent number
US06391885B1

Reaction notes

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