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

HRID 232571Notes

Reaction equation

HRID 232571 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 trifluoroacetic 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 crystallisation from acetone: hexane, gave the title compound as a colourless solid (0.12 g, 21%), m.p. 114°-116° C. Found: C,56.89; H,4.75; N,22.08. C9H9N3O2 requires C,56.54; H,4.75; N,21.98%.

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 crystallisation from acetone

Sources & evidence

ORD record
ord-d8e5be63b5c14323a052a4bf52dfbab5
Source dataset
uspto-grants-1997_01
Patent number
US05591742

Reaction notes

Loading…