Hydrochloric Acid → Palonosetron hydrochloride

HRID 419296ノート

反応式

HRID 419296 の反応式
[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]

参加物

6

反応物 3

HCID 313Hydrochloric AcidHCID 24408BromineHCID 6337614Palonosetron

生成物 1

HCID 6918303Palonosetron hydrochloride

試薬・触媒・溶媒 2

HCID 702Ethanol溶媒2 回HCID 887Methanol溶媒

反応条件

温度
72.5 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-f139e003afcf489ea25009e753bfc272
出典データセット
uspto-grants-2012_01
特許番号
US08093391B2

反応ノート

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