Water → Posaconazole Impurity 326

HRID 512818Notes

Reaction equation

HRID 512818 reaction equation
[OH-].[Na+].O.[CH2:4]([O:11][C@H:12]([C@@H:14]([N:17]1[C:21](=[O:22])[N:20]([C:23]2[CH:28]=[CH:27][C:26]([N:29]3[CH2:34][CH2:33][N:32]([C:35]4[CH:40]=[CH:39][C:38]([OH:41])=[CH:37][CH:36]=4)[CH2:31][CH2:30]3)=[CH:25][CH:24]=2)[CH:19]=[N:18]1)[CH2:15][CH3:16])[CH3:13])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.CC1C=CC(S(O[CH2:53][C@H:54]2[CH2:58][C@:57]([CH2:67][N:68]3[CH:72]=[N:71][CH:70]=[N:69]3)([C:59]3[CH:64]=[CH:63][C:62]([F:65])=[CH:61][C:60]=3[F:66])[O:56][CH2:55]2)(=O)=O)=CC=1>CS(C)=O>[N:68]1([CH2:67][C@@:57]2([C:59]3[CH:64]=[CH:63][C:62]([F:65])=[CH:61][C:60]=3[F:66])[O:56][CH2:55][C@@H:54]([CH2:53][O:41][C:38]3[CH:39]=[CH:40][C:35]([N:32]4[CH2:31][CH2:30][N:29]([C:26]5[CH:27]=[CH:28][C:23]([N:20]6[C:21](=[O:22])[N:17]([C@H:14]([CH2:15][CH3:16])[C@@H:12]([O:11][CH2:4][C:5]7[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=7)[CH3:13])[N:18]=[CH:19]6)=[CH:24][CH:25]=5)[CH2:34][CH2:33]4)=[CH:36][CH:37]=3)[CH2:58]2)[CH:72]=[N:71][CH:70]=[N:69]1

Participants

6

Reactant 4

HCID 962WaterHCID 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 89463936Posaconazole Impurity 326

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
52.5 °C

Procedure

A solution of sodium hydroxide (9.2 g) and water (10 ml) was cooled to 25-35° C. and added dimethyl sulfoxide (350 ml), followed by 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 (50 gms) compound of formula-20 at 25-35° C. The reaction mixture was stirred for 45 minutes at the same temperature. ((3S,5R)-5-((1H-1,2,4-triazol-1-yl)methyl)-5-(2,4-difluoro phenyl)tetrahydrofuran-3-yl)methyl 4-methylbenzenesulfonate (50 μms) compound of formula-10 was added to the above reaction mixture and heated to 45-60° C. The reaction mixture was stirred for 6 hours at the same temperature. After completion of the reaction, the reaction mixture was quenched with water and neutralized with hydrochloric acid. The reaction mixture was stirred for 1 hour at 25-35° C. Filtered the solid and washed with water. Dried the solid to get the title compound. Yield: 79 g

Workup

  1. customformula-20 at 25-35° C
  2. stirringThe reaction mixture was stirred for 6 hours at the same temperature
  3. customAfter completion of the reaction
  4. customthe reaction mixture was quenched with water and neutralized with hydrochloric acid
  5. stirringThe reaction mixture was stirred for 1 hour at 25-35° C
  6. filtrationFiltered the solid
  7. washwashed with water
  8. customDried the solid

Sources & evidence

ORD record
ord-4ec8a7fecbff4859a859f8772d40dc2a
Source dataset
uspto-grants-2015_08
Patent number
US09102664B2

Reaction notes

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