Sodium Hydroxide → 4-Amino-2,6-diethylpyridine-3-carboxylic acid

HRID 1198652Notes

Reaction equation

HRID 1198652 reaction equation
[NH2:1][C:2]([CH2:6][CH3:7])=[CH:3][C:4]#[N:5].[C:8]([CH2:12][C:13]([O:15]C)=O)(=O)[CH2:9][CH3:10].[OH-:17].[Na+]>CO>[NH2:5][C:4]1[CH:3]=[C:2]([CH2:6][CH3:7])[N:1]=[C:8]([CH2:9][CH3:10])[C:12]=1[C:13]([OH:15])=[O:17]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 121699Methyl 3-oxovalerateHCID 714097573-Amino-2-pentenenitrile

Product 1

HCID 200942464-Amino-2,6-diethylpyridine-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Methyl 4-amino-2,6-diethylpyridine-3-carboxylate (3.94 g), itself obtained using an analogous procedure to that described in Tet. Lett., 1990, 3485 but starting from 3-amino-2-pentenenitrile (obtained as described in J. Het. Chem., 1989, 26, 1575) and methyl propionylacetate, is added to a mixture of 2M sodium hydroxide solution (9.5 ml) and methanol (40 ml) and the mixture is heated at reflux for 16 hours. The solution is cooled to ambient temperature and volatile material is removed by evaporation. The residue is partitioned between ethyl acetate and a mixture of 2M hydrochloric acid (9.5 ml) and water (20 ml). The aqueous phase is separated, water is removed by evaporation and the residue is extracted with ethyl acetate/methanol (1:1 v/v). The combined organic extracts are filtered and solvent is removed from the filtrate by evaporation to give 4-amino-2,6-diethylpyridine-3-carboxylic acid (3.46 g) as a yellow-brown foam; NMR (d6 -DMSO): 1.18(m,6H), 2.64(q,2H), 3.12 (q,2H), 6.49(s,1H), 8.28(broad s,2H),; mass spectrum (chemical ionisation, ammonia): 195(M+H)+.

Workup

  1. temperaturethe mixture is heated
  2. temperatureat reflux for 16 hours
  3. customvolatile material is removed by evaporation
  4. customThe residue is partitioned between ethyl acetate
  5. additiona mixture of 2M hydrochloric acid (9.5 ml) and water (20 ml)
  6. customThe aqueous phase is separated
  7. customwater is removed by evaporation
  8. extractionthe residue is extracted with ethyl acetate/methanol (1:1 v/v)
  9. filtrationThe combined organic extracts are filtered
  10. customsolvent is removed from the filtrate by evaporation

Sources & evidence

ORD record
ord-da328fb9b15d45f2b1905fe7b9871b17
Source dataset
uspto-grants-1994_01
Patent number
US05281613

Reaction notes

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