Toluene → Methyl 4-amino-2,6-diethylpyridine-3-carboxylate

HRID 487376Notes

Reaction equation

HRID 487376 reaction equation
[Sn](Cl)(Cl)(Cl)Cl.[NH2:6][C:7]([CH2:11][CH3:12])=[CH:8][C:9]#[N:10].C(C[C:18]([O:20][CH3:21])=[O:19])(=O)CC.C(=O)([O-])[O-].[Na+].[Na+].[C:28]1(C)[CH:33]=[CH:32]C=C[CH:29]=1>CCOCC>[NH2:10][C:9]1[CH:29]=[C:28]([CH2:33][CH3:32])[N:6]=[C:7]([CH2:11][CH3:12])[C:8]=1[C:18]([O:20][CH3:21])=[O:19]

Participants

7

Reactant 5

HCID 1140Toluene2×HCID 10340Sodium CarbonateHCID 24287Tin tetrachlorideHCID 121699Methyl 3-oxovalerateHCID 714097573-Amino-2-pentenenitrile

Product 1

HCID 20094263Methyl 4-amino-2,6-diethylpyridine-3-carboxylate

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

A solution of tin tetrachloride (24 ml) in toluene (70 ml) was added to a stirred solution of 3-amino-2-pentenenitrile (10 g) (obtained as described in J. Het. Chem., 1989, 26, 1575) and methyl propionylacetate (13.4 g) in toluene (150 ml). The mixture was heated at reflux for 6 hours and then stirred at ambient temperature for 16 hours. Saturated sodium carbonate solution was added to the stirred mixture until the aqueous phase was basic (pH>9). Ether (200 ml) was added to the mixture and the precipitated tin salts removed by filtration through diatomaceous earth. The organic phase of the filtrate was separated, washed with sodium chloride solution and dried (MgSO4). Solvent was removed by evaporation and the residue was extracted with hot hexane (3×50 ml). The combined hexane extracts were evaporated and the residue was dissolved in minimum of hot hexane. The solution was then cooled at 4° C. for 16 hours when a yellow solid crystallised. The solid (7.3 g) was collected by filtration and purified by flash chromatography eluting with dichloromethane/methanol (1:19 v/v) to give methyl 4-amino-2,6-diethylpyridine-3-carboxylate (B) (6 g) as a light yellow solid, m.p. 75° C.; NMR (CDCl3): 1.25(t,6H), 2.65(q,2H), 2.95(q,2H), 3.9(s,3H), 5.65(broad s,2H), 6.25(s,1H); mass spectrum (chemical ionisation (CI), ammonia): 209(M+H)+.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 6 hours
  3. customthe precipitated tin salts removed by filtration through diatomaceous earth
  4. customThe organic phase of the filtrate was separated
  5. washwashed with sodium chloride solution
  6. dry with materialdried (MgSO4)
  7. customSolvent was removed by evaporation
  8. extractionthe residue was extracted with hot hexane (3×50 ml)
  9. customThe combined hexane extracts were evaporated
  10. dissolutionthe residue was dissolved in minimum of hot hexane
  11. temperatureThe solution was then cooled at 4° C. for 16 hours when a yellow solid
  12. customcrystallised
  13. filtrationThe solid (7.3 g) was collected by filtration
  14. custompurified by flash chromatography
  15. washeluting with dichloromethane/methanol (1:19 v/v)

Sources & evidence

ORD record
ord-12c49d46b9504d40955e3bba86a7f3dc
Source dataset
uspto-grants-1994_03
Patent number
US05294620

Reaction notes

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