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

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

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)+.