Dimethylformamide → Acetoxymethyl methyl 4-(2',3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate

HRID 1598795Notes

Reaction equation

HRID 1598795 reaction equation
[CH3:1][C:2]1[NH:3][C:4]([CH3:23])=[C:5](CC(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:27])([OH:26])[O-].[Na+].[C:29]([O:32][CH2:33]Cl)(=[O:31])[CH3:30].[CH3:35]N(C=O)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:24]([O:26][CH3:35])=[O:27])=[C:4]([CH3:23])[NH:3][C:2]([CH3:1])=[C:7]1[C:8]([O:10][CH2:33][O:32][C:29](=[O:31])[CH3:30])=[O:9]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 69366Chloromethyl acetateHCID 516892Sodium BicarbonateHCID 668096561,4-Dihydro-2,6-dimethyl-4-(2',3'-dichorophenyl)-5-carboxymethyl-3-pyridinecarboxylic acid

Product 1

HCID 70148229Acetoxymethyl methyl 4-(2',3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylateYield 48%

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 (0.3 g, 0.83 mmol) and sodium bicarbonate (0.14 g, 1.69 mmol)in DMF (15 ml) under nitrogen atmosphere was added chloromethyl acetate (0.137 g, 1.26 mmol). The reaction mixture was heated at 80° C. for 18 h. Workup by evaporation of solvent and addition of water. Extraction with dichloromethane, the extract was dried over sodium sulfate and concentrated. The resulting oil was subjected to flash chromatography [silica gel, dichloromethane--dichloromethane/methanol (9/1) gradient] to give colorless crystals (0.17 g, 48%) mp. 144.5°-147.6° C. 1H-NMR (CDCl3): 7.30-7.04 (Ar, 3H); 5.97 (s, 1H); 5.73 (d, J=5.5 Hz, 1H); 5.69 (d, J=5.5 Hz, 1H); 5.46 (s, 1H); 3.6 (s, 3H); 2.32 (s, 3H); 2.30 (s, 3H); 2.03 (s, 3H). 13 C-NMR (CDCl3): 169.64; 167.63; 165.81; 147.46; 146.77; 143.85; 132.86; 131.15; 129.83; 128.31; 126.98; 103.97; 101.89; 78.73; 50.93; 38.45; 20.80; 19.86; 19.26.

Workup

  1. customWorkup by evaporation of solvent and addition of water
  2. extractionExtraction with dichloromethane
  3. dry with materialthe extract was dried over sodium sulfate
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-cda8481865be49bfac0904d1b0ea53d9
Source dataset
uspto-grants-1998_04
Patent number
US05739152

Reaction notes

Loading…