Dimethylformamide → 3,5-Pyridinedicarboxylic acid, 4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-, 3-methyl 5-((1-oxobutoxy)methyl) ester

HRID 1598796Notes

Reaction equation

HRID 1598796 reaction equation
[CH3:1][C:2]1[NH:3][C:4]([CH3:23])=[C:5]([CH2:19]C(O)=O)[CH:6]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[C:12]=2[Cl:18])[C:7]=1[C:8]([OH:10])=[O:9].[C:24](=O)(O)[O-:25].[Na+].[C:29]([O:34][CH2:35]Cl)(=[O:33])[CH2:30][CH2:31][CH3:32].CN(C=[O:41])C>>[Cl:18][C:12]1[C:13]([Cl:17])=[CH:14][CH:15]=[CH:16][C:11]=1[CH:6]1[C:5]([C:19]([O:25][CH3:24])=[O:41])=[C:4]([CH3:23])[NH:3][C:2]([CH3:1])=[C:7]1[C:8]([O:10][CH2:35][O:34][C:29](=[O:33])[CH2:30][CH2:31][CH3:32])=[O:9]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 516892Sodium BicarbonateHCID 2725008Chloromethyl butanoateHCID 668096561,4-Dihydro-2,6-dimethyl-4-(2',3'-dichorophenyl)-5-carboxymethyl-3-pyridinecarboxylic acid

Product 1

HCID 1539943,5-Pyridinedicarboxylic acid, 4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-, 3-methyl 5-((1-oxobutoxy)methyl) esterYield 66%

Conditions

Temperature
80 °C

Procedure

To a stirred mixture of 1,4-dihydro-2,6-dimethyl-4-(2',3'-dichorophenyl)-5-carboxymethyl-3-pyridinecarboxylic acid (2.62 g, 7.35 mmol) and sodium bicarbonate (1.26 g, 15 mmol) in DMF (130 ml) under nitrogen atmosphere was added chloromethyl butyrate (1.53 g, 11.21 mmol). The reaction mixture was heated at 80° C. for 24 h. Workup by filtration followed by evaporation of solvent. The crude residue was chromatographed on silica gel with 45% ethyl acetate in isooctane. Recrystallization from diisopropylether gave colorless crystals (2.20 g, 66%), mp. 136.2°-138.5° C. 1H-NMR (CDCl3): 7.30-7.03 (m, 3H); 5.89 (s, 1H); 5.74 (d, J=5.5 Hz, 1H); 5.70 (d, J=5.5 Hz, 1H); 5.46 (s, 1H); 3.60 (s, 3H); 2.33 (m, 8H); 1.65-1.55 (m, 2H); 0.90 (t, J=7.4 Hz, 3H). 13C-NMR (CDCl3): 172.25; 167.61; 165.80; 147.43; 146.59; 143.82; 132.89; 131.11; 129.82; 128.30; 126.95; 103.97; 101.99; 78.63; 50.92; 38.49; 35.79; 19.91; 19.30; 18.01; 13.50.

Workup

  1. filtrationWorkup by filtration
  2. customfollowed by evaporation of solvent
  3. customThe crude residue was chromatographed on silica gel with 45% ethyl acetate in isooctane
  4. customRecrystallization from diisopropylether

Sources & evidence

ORD record
ord-6d9b26bfe6cb46478c686d291371dbcd
Source dataset
uspto-grants-1998_04
Patent number
US05739152

Reaction notes

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