Dimethyl Sulfoxide → Posaconazole

HRID 512819Notes

Reaction equation

HRID 512819 reaction equation
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]

Participants

7

Reactant 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

Product 1

HCID 468595PosaconazoleYield 98%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 3776IsopropanolSolvent

Conditions

Temperature
45 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-5956d92c26d74c218223b9dc558212ea
Source dataset
uspto-grants-2015_08
Patent number
US09102664B2

Reaction notes

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