Water → 3-Amino-5-methylpyridine-2-carbonitrile

HRID 1898258Notes

Reaction equation

HRID 1898258 reaction equation
[C:1]([C:3]1[C:8]([N+:9]([O-])=O)=[CH:7][C:6]([CH3:12])=[CH:5][N:4]=1)#[N:2].C([O-])(O)=O.[Na+].O>C(O)(=O)C.CCOC(C)=O.[Fe]>[NH2:9][C:8]1[C:3]([C:1]#[N:2])=[N:4][CH:5]=[C:6]([CH3:12])[CH:7]=1

Participants

7

Reactant 3

HCID 962WaterHCID 516892Sodium BicarbonateHCID 233836945-Methyl-3-nitropicolinonitrile

Product 1

HCID 533953753-Amino-5-methylpyridine-2-carbonitrileYield 76.4%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 176Acetic AcidSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To acetic acid (300 mL) in a 3-neck 2 liter round bottom flask equipped with mechanical stirrer and a thermometer was added Fe powder (99.6 g, 1.78 mol) with stirring at 60° C. 2-Cyano-5-methyl-3-nitropyridine (97 g, 0.59 mol) was dissolved in acetic acid (400 mL) with gentle warming and added to the above reaction mixture drop wise with efficient stirring so that the reaction temperature kept below 80° C. over 3.5 hours. The reaction mixture was further stirred for an addition 30 min, cooled, diluted with EtOAc (750 mL), filtered through celite and washed with EtOAc (1×500 mL, 3×250 mL). Combined EtOAc layers were evaporated to dryness to obtain dark brown solid which was neutralized with saturated NaHCO3 solution (850 mL), after addition of water (250 mL) to obtain homogeneous, this aqueous layer was extracted with EtOAc (1×750 mL, 2×500 mL). Combined EtOAc layers were filtered through small pad of silica gel (sand-SiO2-sand in sintered funnel), dried (Na2SO4) and evaporated to obtain 3-amino-2-cyano-5-methylpyridine (60 g) as yellow solid in 76% yield including ˜10% corresponding amide.

Workup

  1. temperaturewith gentle warming
  2. additionadded to the above reaction mixture drop wise
  3. stirringwith efficient stirring so that the reaction temperature
  4. stirringThe reaction mixture was further stirred for an addition 30 min
  5. temperaturecooled
  6. filtrationfiltered through celite
  7. washwashed with EtOAc (1×500 mL, 3×250 mL)
  8. customCombined EtOAc layers were evaporated to dryness
  9. customto obtain dark brown solid which
  10. customto obtain homogeneous
  11. extractionthis aqueous layer was extracted with EtOAc (1×750 mL, 2×500 mL)
  12. filtrationCombined EtOAc layers were filtered through small pad of silica gel (sand-SiO2-sand in sintered funnel)
  13. dry with materialdried (Na2SO4)
  14. customevaporated

Sources & evidence

ORD record
ord-0e44db0e3d63478393a5bdf09b9f1e60
Source dataset
uspto-grants-2013_08
Patent number
US08519135B2

Reaction notes

Loading…