Ammonium formate → Amlodipine

HRID 1252

Reaktionsgleichung

Reaktionsgleichung von HRID 1252
[CH3:1][O:2][C:3]([C:5]1[CH:6]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[Cl:29])[C:7]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[C:8]([CH2:12][O:13][CH2:14][CH:15]=[N:16]O)[NH:9][C:10]=1[CH3:11])=[O:4].C([O-])=O.[NH4+]>CO.[OH-].[OH-].[Pd+2]>[CH3:1][O:2][C:3]([C:5]1[CH:6]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[Cl:29])[C:7]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[C:8]([CH2:12][O:13][CH2:14][CH2:15][NH2:16])[NH:9][C:10]=1[CH3:11])=[O:4]

Komponenten

5

Edukt 2

HCID 2723923Ammonium formateHCID 730780804-(2-Chlorophenyl)-2-(2-hydroxyimino-ethoxymethyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylic acid 3-ethyl 5-methyl ester

Produkt 1

HCID 2162AmlodipineAusbeute 60,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9942167Palladium hydroxideKatalysatorHCID 887MethanolLösungsmittel

Versuchsvorschrift

A mixture of 4-(2-chlorophenyl)-2-(2-hydroxyimino-ethoxymethyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylic acid 3-ethyl 5-methyl ester (IBa, 150 mg), palladium hydroxide on carbon (10 mg) and ammonium formate (224 mg) in methanol (10 mL) was refluxed for 5 h under a nitrogen atmosphere. On cooling to room temperature, the mixture was filtered through a pad of celite. The filtrate was concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (grade 9385, Merck, 230-400 mesh, 60 Å) using a solvent mixture of dichloromethane and methanol (9:1; 100 mL), and dichloromethane, methanol and ammonium hydroxide (90:10:1; 500 mL) as eluent afforded the title compound (IAa 88 mg).

Aufarbeitung

  1. temperaturewas refluxed for 5 h under a nitrogen atmosphere
  2. filtrationthe mixture was filtered through a pad of celite
  3. concentrationThe filtrate was concentrated in vacuo
  4. customPurification of the residue by flash chromatography on silica gel (grade 9385, Merck, 230-400 mesh, 60 Å)
  5. additiona solvent mixture of dichloromethane and methanol (9:1; 100 mL), and dichloromethane, methanol and ammonium hydroxide (90:10:1; 500 mL) as eluent

Quellen und Nachweise

ORD-Eintrag
ord-db51435d97f64dfb86f4de59e3efb185
Quelldatensatz
uspto-grants-1998_03
Patentnummer
US05723618

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