Dimethyl Sulfoxide → Posaconazole

HRID 512819ノート

反応式

HRID 512819 の反応式
C([O:8][C@H:9]([C@@H:11]([N:14]1[C:18](=[O:19])[N:17]([C:20]2[CH:25]=[CH:24][C:23]([N:26]3[CH2:31][CH2:30][N:29]([C:32]4[CH:37]=[CH:36][C:35](O)=[CH:34][CH:33]=4)[CH2:28][CH2:27]3)=[CH:22][CH:21]=2)[CH:16]=[N:15]1)[CH2:12][CH3:13])[CH3:10])C1C=CC=CC=1.CS(C)=O.[OH-].[Na+].[N:45]1([CH2:50][C@@:51]2([C:68]3[CH:73]=[CH:72][C:71]([F:74])=[CH:70][C:69]=3[F:75])[O:55][CH2:54][C@@H:53]([CH2:56][O:57]S(C3C=CC(C)=CC=3)(=O)=O)[CH2:52]2)[CH:49]=[N:48][CH:47]=[N:46]1>C(O)(C)C.O>[CH3:13][CH2:12][C@H:11]([N:14]1[N:15]=[CH:16][N:17]([C:20]2[CH:25]=[CH:24][C:23]([N:26]3[CH2:27][CH2:28][N:29]([C:32]4[CH:33]=[CH:34][C:35]([O:57][CH2:56][C@@H:53]5[CH2:54][O:55][C@:51]([C:68]6[CH:73]=[CH:72][C:71]([F:74])=[CH:70][C:69]=6[F:75])([CH2:50][N:45]6[N:46]=[CH:47][N:48]=[CH:49]6)[CH2:52]5)=[CH:36][CH:37]=4)[CH2:30][CH2:31]3)=[CH:22][CH:21]=2)[C:18]1=[O:19])[C@@H:9]([OH:8])[CH3:10]

参加物

7

反応物 4

HCID 679Dimethyl SulfoxideHCID 14798Sodium HydroxideHCID 108956292,5-Anhydro-1,3,4-trideoxy-2-C-(2,4-difluorophenyl)-4-((((4-methylphenyl)sulfonyl)oxy)methyl)-1-(1H-1,2,4-triazol-1-yl)-D-threo-pentitolHCID 462232972-((1S,2S)-1-Ethyl-2-(phenylmethoxy)propyl)-2,4-dihydro-4-(4-(4-(4-hydroxyphenyl)-1-piperazinyl)phenyl)-3H-1,2,4-triazol-3-one

生成物 1

HCID 468595Posaconazole収率 98%

試薬・触媒・溶媒 2

HCID 962Water溶媒2 回HCID 3776Isopropanol溶媒

反応条件

温度
45 °C

実験手順

Added 1-((2S,3S)-2-(benzyloxy)pentan-3-yl)-4-(4-(4-(4-hydroxyphenyl) piperazin-1-yl)phenyl)-1H-1,2,4-triazol-5(4H)-one compound of formula-20 (35 g) to a mixture of dimethylsulfoxide (350 ml) and sodium hydroxide (3.4 g) and water (7 ml) at 25-30° C. and stirred for 45 minutes at 25-30° C. ((3S,5R)-5-((1H-1,2,4-triazol-1-yl)methyl)-5-(2,4-difluorophenyl)tetrahydrofuran-3-yl)methyl-4-methylbenzenesulfonate compound of formula-10 (31.5 g) was added to the above reaction mixture at 25-30° C. and heated the reaction mixture to 45° C. and stirred for 5 hours at the same temperature. After completion of the reaction, cooled the reaction mixture to room temperature and water was added to the reaction mixture. The reaction mixture was extracted twice with ethyl acetate. Adjusted the pH of the reaction mixture with aqueous hydrochloric acid solution. The organic layers were washed with sodium chloride solution. Distilled off the solvent under reduced pressure to get the compound as residue. Dissolved the obtained residue in isopropanol (320 ml) at 45-50° C. Filtered the solid, washed with isopropanol and dried aerially to get the title compound. Yield: 98%; Purity by HPLC: 99.5%; M.R: 117° C.-119° C.

後処理

  1. additionwas added to the above reaction mixture at 25-30° C.
  2. customAfter completion of the reaction
  3. temperaturecooled the reaction mixture to room temperature
  4. extractionThe reaction mixture was extracted twice with ethyl acetate
  5. washThe organic layers were washed with sodium chloride solution
  6. distillationDistilled off the solvent under reduced pressure
  7. customto get the compound as residue
  8. filtrationFiltered the solid
  9. washwashed with isopropanol
  10. customdried aerially

出典と根拠

ORDレコード
ord-5956d92c26d74c218223b9dc558212ea
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…