Hydrochloric Acid → Palonosetron hydrochloride
Reaction equation
[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].BrN1C(=O)CCC1=O>CO.C(O)C.C(O)C.CO>[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]Participants
Conditions
- Temperature
- 72.5 °C
Procedure
The diastereomeric palonosetron (VIII) (96.0 g) as obtained above 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 N-bromosuccinimide (500 mg) was added at reflux. The solution was then cooled to 0 to 5° C. and 53.0 g of the precipitated crude palonosetron hydrochloride (I) were isolated by filtration. This obtained crude palonosetron hydrochloride (I) showing 93.74% of the desired (3aS,S) isomer, 6.19% of the undesired (3aR,S) isomer (Ia) and 0.2% of unreacted compound (IIa), when treated again with 200 mg of N-bromosuccinimide in ethanol-methanol mixture yielded 34.0 g of the title product (I) which was found to contain 99.63% of the titled compound (I), 0.32% of the undesired (3aR,S) isomer (Ia) and 0.05% of unreacted intermediate (IIa) by HPLC analysis.
Workup
- temperatureat reflux
- temperatureThe solution was then cooled to 0 to 5° C.
- custom53.0 g of the precipitated crude palonosetron hydrochloride (I)
- customwere isolated by filtration
- customThis obtained crude palonosetron hydrochloride (I)
Sources & evidence
- ORD record
- ord-4c12d3b7fa08477facfe7879523d5468
- Source dataset
- uspto-grants-2012_01
- Patent number
- US08093391B2
Reaction notes
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