Dimethyl Sulfoxide → Citalopram

HRID 585345Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 585345
[H-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][C:7]([CH:10]2[C:18]3[C:13](=[CH:14][C:15]([C:19]#[N:20])=[CH:16][CH:17]=3)[CH2:12][O:11]2)=[CH:6][CH:5]=1.[CH3:21][N:22]([CH3:27])[CH2:23][CH2:24][CH2:25]Cl.CS(C)=O>C1COCC1.C1(C)C=CC=CC=1>[CH3:21][N:22]([CH3:27])[CH2:23][CH2:24][CH2:25][C:10]1([C:7]2[CH:8]=[CH:9][C:4]([F:3])=[CH:5][CH:6]=2)[C:18]2[C:13](=[CH:14][C:15]([C:19]#[N:20])=[CH:16][CH:17]=2)[CH2:12][O:11]1

Komponenten

7

Edukt 4

HCID 679Dimethyl SulfoxideHCID 24758Sodium hydrideHCID 669603-Chloro-N,N-dimethyl-1-propanamineHCID 98561591-(4'-Fluorophenyl)-1,3-DihydroIsobenzofuran-5-Carbonitrile

Produkt 1

HCID 2771CitalopramAusbeute 51,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1140TolueneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

60% Sodium hydride (0.92 g) was dispersed in THF (30 ml). To the obtained suspension was added dropwise a solution of 1-(4′-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (4.80 g) in THF (10 ml) at 40-50° C. The mixture was stirred at the same temperature for 30 min, and a solution of 3-dimethylaminopropyl chloride (3.2 g) in toluene (20 ml) was added dropwise, which was followed by stirring for 10 min. Then, dimethyl sulfoxide (30 ml) was further added dropwise and the mixture was stirred at 65-70° C. for 3 hr. The reaction mixture was poured into ice water (200 ml) and extracted 3 times with toluene (60 ml). The organic layer was extracted twice with 20% aqueous acetic acid (60 ml). The aqueous layer was neutralized, extracted twice with toluene (60 ml) and washed with water. Anhydrous potassium carbonate (2 g) and silica gel (2 g) were added and the mixture was stirred and filtered. The solvent was evaporated to give 1-(3′-dimethylaminopropyl)-1-(4′-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (citalopram base) as a viscous oil (3.37 g, 51.6%).

Aufarbeitung

  1. stirringby stirring for 10 min
  2. stirringthe mixture was stirred at 65-70° C. for 3 hr
  3. extractionextracted 3 times with toluene (60 ml)
  4. extractionThe organic layer was extracted twice with 20% aqueous acetic acid (60 ml)
  5. extractionextracted twice with toluene (60 ml)
  6. washwashed with water
  7. additionAnhydrous potassium carbonate (2 g) and silica gel (2 g) were added
  8. stirringthe mixture was stirred
  9. filtrationfiltered
  10. customThe solvent was evaporated

Quellen und Nachweise

ORD-Eintrag
ord-c824f135f22a49f3b2845b26f249ac5f
Quelldatensatz
uspto-grants-2005_08
Patentnummer
US06930211B2

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