Hydrochloric Acid → Posaconazole

HRID 512817ノート

反応式

HRID 512817 の反応式
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]

参加物

5

反応物 2

HCID 313Hydrochloric AcidHCID 89463936Posaconazole Impurity 326

生成物 1

HCID 468595Posaconazole収率 75%

試薬・触媒・溶媒 2

HCID 23938Palladium触媒HCID 887Methanol溶媒

反応条件

温度
30 °C

実験手順

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%.

後処理

  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

出典と根拠

ORDレコード
ord-131035304ff74c4db19ea6adf7a94ddf
出典データセット
uspto-grants-2015_08
特許番号
US09102664B2

反応ノート

読み込み中…