Hydrochloric Acid → Palonosetron hydrochloride

HRID 419296노트

반응식

HRID 419296 반응식
[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]

참가 물질

6

반응물 3

HCID 313Hydrochloric AcidHCID 24408BromineHCID 6337614Palonosetron

생성물 1

HCID 6918303Palonosetron hydrochloride

시약·촉매·용매 2

HCID 702Ethanol용매2회HCID 887Methanol용매

반응 조건

온도
72.5 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-f139e003afcf489ea25009e753bfc272
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08093391B2

반응 노트

불러오는 중…