Water → (-)-1-Ethoxymethyl-2,6-dimethyl-3-carbomethoxy-4-(3-nitrophenyl)-5-carboxy-1,4-dihydropyridine

HRID 34417

Reaction equation

HRID 34417 reaction equation
[Na].O.[CH2:3]([O:5][CH2:6][N:7]1[C:12]([CH3:13])=[C:11]([C:14]([O:16]C)=[O:15])[CH:10]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([N+:24]([O-:26])=[O:25])[CH:19]=2)[C:9]([C:27]([O:29][CH3:30])=[O:28])=[C:8]1[CH3:31])[CH3:4]>CN(C)CC(O)C.C1C=CC=CC=1>[CH2:3]([O:5][CH2:6][N:7]1[C:12]([CH3:13])=[C:11]([C:14]([OH:16])=[O:15])[CH:10]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([N+:24]([O-:26])=[O:25])[CH:19]=2)[C:9]([C:27]([O:29][CH3:30])=[O:28])=[C:8]1[CH3:31])[CH3:4]

Participants

6

Reactant 3

HCID 962WaterHCID 5360545Sodium2×HCID 126029671-Ethoxymethyl-2,6-dimethyl-3,5-di(carbomethoxy)-4-(3-nitrophenyl)-1,4-dihydropyridine

Product 1

HCID 12602968(-)-1-Ethoxymethyl-2,6-dimethyl-3-carbomethoxy-4-(3-nitrophenyl)-5-carboxy-1,4-dihydropyridine

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 37511DimepranolSolvent2×

Conditions

Temperature
0 °C

Procedure

Optically active dihydropyridine acid derivatives are prepared as described by T. Shibanuma, et al., Chem. Pharm. Bull., 28, 2809-2812 (1980). 2,6-Dimethyl-3,5-di(carbomethoxy)-4-(3-nitrophenyl)-1,4-dihydropyridine is prepared by the Hantzsch method (Ann. Chim., 215, 1 (1882)), then reacted with chloromethoxyethane and NaH to produce 1-ethoxymethyl-2,6-dimethyl-3,5-di(carbomethoxy)-4-(3-nitrophenyl)-1,4-dihydropyridine. Sodium (13.3 g) is added to 1-dimethylamino-2-propanol (150 mL) and the mixture stirred for 1 h. A solution of H2O (3.8 mL) in 1-dimethylamino-2-propanol (40 mL) is added dropwise, and the solution heated to dissolve any remaining sodium. A solution of 1-ethoxymethyl-2,6-dimethyl-3,5-di(carbomethoxy)-4-(3-nitrophenyl)-1,4-dihydropyridine (38 g) in benzene (190 mL) is then added with cooling to 0° C., and the mixture stirred for 3 h. The solvent is then removed by evaporation and the residue acidified to pH 2 by adding 3N HCl in a dry ice-acetone bath. The aqueous solution is then extracted with CHCl3, and the extract washed with water, dried, and concentrated to yield racemic 1-ethoxymethyl-2,6-dimethyl-3-carbomethoxy-4-(3-nitrophenyl)-5-carboxy-1,4-dihydropyridine. The product is then dissolved in methanol (200 mL) and cinchonidine and the solvent removed. The resulting salt is then dissolved in hot ethanol (150 mL) and allowed to stand at room temperature overnight. The crystals formed are recrystallized from EtOH, treated with 0.1N HCl, and extracted with CHCl3 to produce (-)-1-ethoxymethyl-2,6-dimethyl-3-carbomethoxy-4-(3-nitrophenyl)-5-carboxy-1,4-dihydropyridine (mp=134°-135°, αD22 =-16.00°). The other isomer may be recovered from the original crystallization solvent.

Workup

  1. temperaturethe solution heated
  2. stirringthe mixture stirred for 3 h
  3. customThe solvent is then removed by evaporation
  4. additionby adding 3N HCl in a dry ice-acetone bath
  5. extractionThe aqueous solution is then extracted with CHCl3
  6. washthe extract washed with water
  7. customdried
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-79a05f6e03a141d1962944f5b0a5bde7
Source dataset
uspto-grants-1988_08
Patent number
US04761420

Linked notes

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