Dimethyl Sulfoxide → Posaconazole

HRID 512819Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 512819
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]

Komponenten

7

Edukt 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

Produkt 1

HCID 468595PosaconazoleAusbeute 98 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittel2×HCID 3776IsopropanolLösungsmittel

Reaktionsbedingungen

Temperatur
45 °C

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-5956d92c26d74c218223b9dc558212ea
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09102664B2

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