Isopropanol → Nilvadipine

HRID 1721024

Reaktionsgleichung

Reaktionsgleichung von HRID 1721024
P(Cl)(Cl)(Cl)(Cl)Cl.[C:7]([C:10]1[CH:11]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([N+:29]([O-:31])=[O:30])[CH:24]=2)[C:12]([C:19]([O:21][CH3:22])=[O:20])=[C:13]([C:17]#[N:18])[NH:14][C:15]=1[CH3:16])([OH:9])=[O:8].[CH:32](O)([CH3:34])[CH3:33].C(=O)([O-])[O-].[Na+].[Na+]>C(Cl)Cl>[C:17]([C:13]1[NH:14][C:15]([CH3:16])=[C:10]([C:7]([O:9][CH:32]([CH3:34])[CH3:33])=[O:8])[CH:11]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([N+:29]([O-:31])=[O:30])[CH:24]=2)[C:12]=1[C:19]([O:21][CH3:22])=[O:20])#[N:18]

Komponenten

6

Edukt 4

HCID 3776IsopropanolHCID 10340Sodium CarbonateHCID 24819Phosphorus pentachlorideHCID 153887666-Cyano-5-methoxycarbonyl-2-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid

Produkt 1

HCID 4494NilvadipineAusbeute 95,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

Phosphorus pentachloride (2.46 g) was added to a suspension of (+)-methyl 5-carboxy-2-cyano-6-methyl-4-(3-nitrophenyl) -1,4-dihydropyridine-3-carboxylate (3.12 g) in methylene chloride (30 ml) under ice-cooling, and the mixture was stirred for 30 minutes. Then, a solution of isopropyl alcohol (1.4 g) in methylene chloride (10 ml) was added dropwise thereto over a period of 10 minutes. After being stirred for 20 minutes, 5% aqueous sodium carbonate (30 ml ) was added to the reaction solution and then stirred at ambient temperature for an hour. The organic layer was separated and the aqueous layer was extracted with methylene chloride. The combined organic layer was washed with brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by column chromatography on silica gel (75 g) using a mixture of benzene and ethyl acetate (10:1) as an eluent. The eluate was evaporated in vacuo and the residue was crystallized from diisopropyl ether to give (+)-5-isopropyl 3-methyl 2-cyano-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate (3.34 g).

Aufarbeitung

  1. temperaturecooling
  2. waitover a period of 10 minutes
  3. stirringAfter being stirred for 20 minutes
  4. stirringstirred at ambient temperature for an hour
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted with methylene chloride
  7. washThe combined organic layer was washed with brine
  8. dry with materialdried over magnesium sulfate
  9. customevaporated in vacuo
  10. customThe residue was purified by column chromatography on silica gel (75 g)
  11. additiona mixture of benzene and ethyl acetate (10:1) as an eluent
  12. customThe eluate was evaporated in vacuo
  13. customthe residue was crystallized from diisopropyl ether

Quellen und Nachweise

ORD-Eintrag
ord-8ee56fc9a443406c9f89fe63cd33a383
Quelldatensatz
uspto-grants-1996_04
Patentnummer
US05508413

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