Sodium Bicarbonate → HCID 10814962, compound

HRID 1489427Notes

Reaction equation

HRID 1489427 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@:9]([OH:40])([CH2:32][Si](OC(C)C)(C)C)[C@H:10]([N:12]1[C:16](=[O:17])[N:15]([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH2:25][C:26]([F:31])([F:30])[CH:27]([F:29])[F:28])=[CH:20][CH:19]=2)[CH:14]=[N:13]1)[CH3:11].C(=O)([O-])[OH:42].[Na+]>CO.O1CCCC1.OO>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@:9]([OH:40])([CH2:32][OH:42])[C@H:10]([N:12]1[C:16](=[O:17])[N:15]([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH2:25][C:26]([F:31])([F:30])[CH:27]([F:29])[F:28])=[CH:20][CH:19]=2)[CH:14]=[N:13]1)[CH3:11]

Participants

6

Reactant 2

HCID 516892Sodium BicarbonateHCID 10674949HCID 10674949, compound

Product 1

HCID 10814962HCID 10814962, compoundYield 90.5%

Reagents, catalysts & solvents 3

HCID 784Hydrogen PeroxideSolventHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

2-[(1R,2S)-2-(2,4-Difluorophenyl)-2-hydroxy-3-(isopropoxydimethylsilyl)-1-methylpropyl]-4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-3(2H,4H)-1,2,4-triazolone (11 g) was dissolved in a mixture of methanol and tetrahydrofuran (1:1, 90 ml), to which 19.2 ml of 30% aqueous hydrogen peroxide and 1.57 g of sodium hydrogencarbonate were added. Then, the mixture was heated at 70° to 80° C. for 90 minutes. The reaction solution was cooled and extracted with a mixture of 500 ml of ethyl acetate and 100 ml of diisopropyl ether. The extract was washed with 100 ml of water, an aqueous solution of Na2S2O3 (50 ml×2) and 50 ml of an aqueous solution of sodium chloride successively, and dried over magnesium sulfate. After the solvent was distilled off under reduced pressure, the residue was recrystallized from 50 ml of diisopropyl ether to give 8.27 g of 2-[(1R,2S)-2-(2,4-difluorophenyl)-2,3-dihydroxy-1-methylpropyl]-4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-3(2H,4H)-1,2,4-triazolone as colorless prisms. The mother liquor of recrystallization was submitted to silica gel chromatography (silica gel: 40 g, eluent; hexane:ethyl acetate=1:1). The resultant was recrystallized from diisopropyl ether to give 0.33 g of the above compound (total yield: 93.7%).

Workup

  1. additionwere added
  2. temperatureThen, the mixture was heated at 70° to 80° C. for 90 minutes
  3. temperatureThe reaction solution was cooled
  4. extractionextracted with a mixture of 500 ml of ethyl acetate and 100 ml of diisopropyl ether
  5. washThe extract was washed with 100 ml of water
  6. dry with materialan aqueous solution of Na2S2O3 (50 ml×2) and 50 ml of an aqueous solution of sodium chloride successively, and dried over magnesium sulfate
  7. distillationAfter the solvent was distilled off under reduced pressure
  8. customthe residue was recrystallized from 50 ml of diisopropyl ether

Sources & evidence

ORD record
ord-17be780dbf0246b1ba87eb9e7c265990
Source dataset
uspto-grants-1997_10
Patent number
US05677464

Reaction notes

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