Hydrochloric Acid → Palonosetron hydrochloride

HRID 419296Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 419296
[CH:1]1[CH:6]=[C:5]2[C:7]([N:9]([C@H:15]3[CH:20]4[CH2:21][CH2:22][N:17]([CH2:18][CH2:19]4)[CH2:16]3)[CH2:10][C@H:11]3[CH2:12][CH2:13][CH2:14][C:3](=[C:4]23)[CH:2]=1)=[O:8].[ClH:23].BrBr>CO.C(O)C>[CH:1]1[CH:6]=[C:5]2[C:7]([N:9]([C@H:15]3[CH:20]4[CH2:21][CH2:22][N:17]([CH2:18][CH2:19]4)[CH2:16]3)[CH2:10][C@H:11]3[CH2:12][CH2:13][CH2:14][C:3](=[C:4]23)[CH:2]=1)=[O:8].[ClH:23]

Komponenten

6

Edukt 3

HCID 313Hydrochloric AcidHCID 24408BromineHCID 6337614Palonosetron

Produkt 1

HCID 6918303Palonosetron hydrochloride

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 702EthanolLösungsmittel2×HCID 887MethanolLösungsmittel

Reaktionsbedingungen

Temperatur
72.5 °C

Versuchsvorschrift

The diastereomeric palonosetron (VIII) (5.0 g) showing 54.06% of the desired (S, S) isomer, 42.13% of the undesired (3aR, S) isomer (Ia) and 1.04% of unreacted compound (IIa) was dissolved in 5% methanol in ethanol mixture (4.2 volumes). To it hydrochloric acid in ethanol was added and was heated to 70-75° C. Then neat liquid bromine (100 mg) was added at reflux. The solution was then cooled to 0 to 5° C. and 2.2 g of the precipitated crude palonosetron hydrochloride (I) was isolated by filtration. This obtained crude palonosetron hydrochloride (I) showing 96.41% of the desired (3aS, S) isomer, 3.59% of the undesired (3aR, S) isomer (Ia) and no unreacted compound (IIa) on HPLC, was then crystallized twice from ethanol-methanol mixture to give 1.5 g of the title product (I) which was found to contain 99.62% of the titled compound (I) and 0.38% (3aR, S) isomer (Ia) while no unreacted intermediate (IIa) could be detected by HPLC analysis.

Aufarbeitung

  1. temperatureat reflux
  2. temperatureThe solution was then cooled to 0 to 5° C.
  3. custom2.2 g of the precipitated crude palonosetron hydrochloride (I)
  4. customwas isolated by filtration
  5. customThis obtained crude palonosetron hydrochloride (I)
  6. customno unreacted compound (IIa) on HPLC, was then crystallized twice from ethanol-methanol mixture

Quellen und Nachweise

ORD-Eintrag
ord-f139e003afcf489ea25009e753bfc272
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08093391B2

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