Hydrochloric Acid → Posaconazole

HRID 512817노트

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HRID 512817 반응식
Cl.[N:2]1([CH2:7][C@@:8]2([C:52]3[CH:57]=[CH:56][C:55]([F:58])=[CH:54][C:53]=3[F:59])[O:12][CH2:11][C@@H:10]([CH2:13][O:14][C:15]3[CH:20]=[CH:19][C:18]([N:21]4[CH2:26][CH2:25][N:24]([C:27]5[CH:32]=[CH:31][C:30]([N:33]6[C:37](=[O:38])[N:36]([C@H:39]([CH2:50][CH3:51])[C@@H:40]([O:42]CC7C=CC=CC=7)[CH3:41])[N:35]=[CH:34]6)=[CH:29][CH:28]=5)[CH2:23][CH2:22]4)=[CH:17][CH:16]=3)[CH2:9]2)[CH:6]=[N:5][CH:4]=[N:3]1>CO.[Pd]>[CH3:51][CH2:50][C@H:39]([N:36]1[N:35]=[CH:34][N:33]([C:30]2[CH:31]=[CH:32][C:27]([N:24]3[CH2:23][CH2:22][N:21]([C:18]4[CH:17]=[CH:16][C:15]([O:14][CH2:13][C@@H:10]5[CH2:11][O:12][C@:8]([C:52]6[CH:57]=[CH:56][C:55]([F:58])=[CH:54][C:53]=6[F:59])([CH2:7][N:2]6[N:3]=[CH:4][N:5]=[CH:6]6)[CH2:9]5)=[CH:20][CH:19]=4)[CH2:26][CH2:25]3)=[CH:28][CH:29]=2)[C:37]1=[O:38])[C@@H:40]([OH:42])[CH3:41]

참가 물질

5

반응물 2

HCID 313Hydrochloric AcidHCID 89463936Posaconazole Impurity 326

생성물 1

HCID 468595Posaconazole수율 75%

시약·촉매·용매 2

HCID 23938Palladium촉매HCID 887Methanol용매

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온도
30 °C

실험 절차

5N hydrochloric acid (72 ml) and 10% Pd—C(10 g) were added to a solution of 4-(4-(4-(4-(((3R,5R)-5-((1H-1,2,4-triazol-1-yl)methyl)-5-(2,4-difluorophenyl)tetrahydro furan-3-yl)methoxy)phenyl)piperazin-1-yl)phenyl)-1-((2S,3R)-2-(benzyloxy)pentan-3-yl)-1H-1,2,4-triazol-5(4H)-one compound of formula-21 (42 g) in methanol (420 ml). The reaction mixture was hydrogenated for 5 hours under a hydrogen gas pressure of 4-5 kg/cm2 at 50°. After completion of reaction, the catalyst was filtered off and washed with methanol. pH of the filtrate was adjusted to ˜7.0 using 4N sodium hydroxide. Water was added to the reaction mixture and stirred for 2 hours at 25-35° C. Filtered the separated solid and washed with water. The obtained solid was dissolved in acetone (320 ml) and stirred at reflux temperature for 30 minutes. Filtered the undissolved product and added water to the filtrate and stirred the reaction mixture for 4 hours at 25-35° C. Filtered the separated solid and washed with water. Further the solid was recrystallized from isopropyl alcohol to get the title compound. Purity by HPLC: 99.85%; Yield: 75.0%: Chiral purity by HPLC: 99.82%.

후처리

  1. customat 50°
  2. customAfter completion of reaction
  3. filtrationthe catalyst was filtered off
  4. washwashed with methanol
  5. additionWater was added to the reaction mixture
  6. filtrationFiltered the separated solid
  7. washwashed with water
  8. dissolutionThe obtained solid was dissolved in acetone (320 ml)
  9. stirringstirred
  10. temperatureat reflux temperature for 30 minutes
  11. filtrationFiltered the undissolved product
  12. additionadded water to the filtrate
  13. stirringstirred the reaction mixture for 4 hours at 25-35° C
  14. filtrationFiltered the separated solid
  15. washwashed with water
  16. customFurther the solid was recrystallized from isopropyl alcohol

출처 및 근거

ORD 기록
ord-131035304ff74c4db19ea6adf7a94ddf
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09102664B2

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