Hydrochloric Acid → Palonosetron hydrochloride

HRID 419297Notes

Reaction equation

HRID 419297 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>[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

6

Reactant 3

HCID 313Hydrochloric AcidHCID 67184N-bromobutanimideHCID 6337614Palonosetron

Product 1

HCID 6918303Palonosetron hydrochloride

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 887MethanolSolvent

Conditions

Temperature
72.5 °C

Procedure

The diastereomeric palonosetron (VIII) (16.5 g) 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 (140 mg) was added at reflux. The solution was then cooled to 0 to 5° C. and 9.0 g of the precipitated crude palonosetron hydrochloride (I) were isolated by filtration. This obtained crude palonosetron hydrochloride (I) showing 95.90% of the desired (3aS,S) isomer, 3.10% of the undesired (3aR,S) isomer (Ia) and 0.04% of unreacted compound (IIa), when crystallized twice from ethanol-methanol mixture yielded 5.0 g of the title product (I) which was found to contain 99.66% of the titled compound (I), 0.29% of (3aR,S) isomer (Ia) and intermediate (IIa) below detection limit by HPLC analysis.

Workup

  1. temperatureat reflux
  2. temperatureThe solution was then cooled to 0 to 5° C.
  3. custom9.0 g of the precipitated crude palonosetron hydrochloride (I)
  4. customwere isolated by filtration
  5. customThis obtained crude palonosetron hydrochloride (I)
  6. customcrystallized twice from ethanol-methanol mixture

Sources & evidence

ORD record
ord-411a5d9ef8934038aa716576c6a45cf1
Source dataset
uspto-grants-2012_01
Patent number
US08093391B2

Reaction notes

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