Potassium Carbonate → 1,4-Dihydro-2,6-dimethyl-4-(m-nitrophenyl)-pyridine-3,5-dicarboxylic acid 3-{2-[p-(2-amino-2-methylpropoxy)-phenoxy]-ethyl}-ester 5-methyl ester

HRID 620087Notes

Reaction equation

HRID 620087 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:10]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([N+:17]([O-:19])=[O:18])[CH:12]=2)[C:9]([C:20]([OH:22])=[O:21])=[C:8]([CH3:23])[NH:7][C:6]=1[CH3:24])=[O:4].Br[CH2:26][CH2:27][O:28][C:29]1[CH:34]=[CH:33][C:32]([O:35][CH2:36][C:37]([NH:40]C(OC(C)(C)C)=O)([CH3:39])[CH3:38])=[CH:31][CH:30]=1.C(=O)([O-])[O-].[K+].[K+]>[Cl-].C([N+](CC)(CC)CC1C=CC=CC=1)C.C(#N)C>[CH3:1][O:2][C:3]([C:5]1[CH:10]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([N+:17]([O-:19])=[O:18])[CH:12]=2)[C:9]([C:20]([O:22][CH2:26][CH2:27][O:28][C:29]2[CH:34]=[CH:33][C:32]([O:35][CH2:36][C:37]([NH2:40])([CH3:39])[CH3:38])=[CH:31][CH:30]=2)=[O:21])=[C:8]([CH3:23])[NH:7][C:6]=1[CH3:24])=[O:4]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 1733222,6-Dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid monomethyl esterHCID 212484381-(2-Bromoethoxy)-4-[2-(tertiary butoxycarbonylamino)-2-methylpropoxy]-benzene

Product 1

HCID 703937091,4-Dihydro-2,6-dimethyl-4-(m-nitrophenyl)-pyridine-3,5-dicarboxylic acid 3-{2-[p-(2-amino-2-methylpropoxy)-phenoxy]-ethyl}-ester 5-methyl ester

Reagents, catalysts & solvents 2

HCID 66133Benzyl triethylammonium chlorideCatalystHCID 6342AcetonitrileSolvent

Procedure

16.6 g (50 mmol) of 1,4-dihydro-2,6-dimethyl-4-(m-nitrophenyl)-3,5-pyridine-dicarboxylic acid monomethyl ester, 19.4 g (50 mmol) of crude 1-(2-bromoethoxy)-4-[2-(tertiary butoxycarbonylamino)-2-methylpropoxy]-benzene 13.8 g of potassium carbonate and 0.6 g of triethylbenzylammonium chloride are heated at boiling in 500 ml of acetonitrile for 16 hours while stirring and under reflux. The reaction mixture is filtered, concentrated by evaporation and dissolved in 500 ml of ethyl acetate. After washing with 100 ml of water and drying (MgSO4), the solvent is evaporated off and 50 ml of dioxan and 100 ml of formic acid are added to the crude residue without the latter being further purified, and the whole is left to stand in the dark at room temperature for 7-10 hours. After concentration by evaporation in vacuo, the residue is dissolved in 2N hydrochloric acid and the solution is extracted with toluene. The aqueous phase is rendered alkaline with 2N sodium hydroxide solution and extracted with ethyl acetate. After drying the solution (MgSO4) and concentration by evaporation, an oil is obtained from which 1,4-dihydro-2,6-dimethyl-4-(m-nitrophenyl)-pyridine-3,5-dicarboxylic acid 3-{2-[p-(2-amino-2-methylpropoxy)-phenoxy]-ethyl}-ester 5-methyl ester, which has a melting point of 141°-142°, is obtained from acetonitrile.

Workup

  1. temperatureunder reflux
  2. filtrationThe reaction mixture is filtered
  3. concentrationconcentrated by evaporation
  4. dissolutiondissolved in 500 ml of ethyl acetate
  5. washAfter washing with 100 ml of water
  6. dry with materialdrying (MgSO4)
  7. customthe solvent is evaporated off
  8. addition50 ml of dioxan and 100 ml of formic acid are added to the crude residue without the latter
  9. waitthe whole is left
  10. customdark at room temperature
  11. customfor 7-10 hours
  12. concentrationAfter concentration
  13. customby evaporation in vacuo
  14. dissolutionthe residue is dissolved in 2N hydrochloric acid
  15. extractionthe solution is extracted with toluene
  16. extractionextracted with ethyl acetate
  17. customAfter drying
  18. concentrationthe solution (MgSO4) and concentration
  19. customby evaporation

Sources & evidence

ORD record
ord-ed6fdb16a58d4e39919980147851310a
Source dataset
uspto-grants-1989_04
Patent number
US04818766

Reaction notes

Loading…