Phosphate → (2RS,3RS)-2-(2,4-difluorophenyl)-3-mercapto-1-(1H-1,2,4-triazol-1-yl)-2-butanol

HRID 273769Notes

Reaction equation

HRID 273769 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1([CH2:13][N:14]2[CH:18]=[N:17][CH:16]=[N:15]2)[CH:11]([CH3:12])[O:10]1.[SH:19]CCC(OC)=O.C[O-].[Na+].CO.C[O-].[Na+].P([O-])([O-])([O-])=O>CO.O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:10])([CH:11]([SH:19])[CH3:12])[CH2:13][N:14]1[CH:18]=[N:17][CH:16]=[N:15]1

Participants

8

Reactant 5

HCID 1061PhosphateHCID 18050Methyl 3-mercaptopropionate2×HCID 10942334Sodium MethoxideHCID 147064491-((2-(2,4-Difluorophenyl)-3-methyl-2-oxiranyl)methyl)-1H-1,2,4-triazoleHCID 23694274Sodium methanolate methanol

Product 1

HCID 9882302(2RS,3RS)-2-(2,4-difluorophenyl)-3-mercapto-1-(1H-1,2,4-triazol-1-yl)-2-butanol

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A solution of (2RS,3SR)-2-(2,4-difluorophenyl)-3-methyl-2-(1H-1,2,4-triazol-1-yl)methyloxirane (7.0 g), methyl 3-mercaptopropionate (30.8 ml) and 28% sodium methylate-methanol solution (19.6 ml) in methanol (210 ml) was refluxed for 2 hours. 28% Sodium methylate methanolic solution (9.8 ml) was added to the resultant solution and refluxed for 1 hour. Thereafter, methyl 3-mercaptopropionate (4 ml) was added to the resultant solution and refluxed for 2 hours. After ice-cooling, the reaction mixture was diluted with water (100 ml) and neutralized with 5% aqueous phosphate solution, and extracted with methylene chloride (200 ml×2). The extract was dried over anhydrous sodium sulfate and distilled off the solvent under reduced pressure. The residue was subjected to a silica gel column chromatography (4×50cm), eluting with ethyl acetate-hexane (3:1). The collected fractions of the object compound were concentrated and ethyl ether was added to the residue to obtain (2RS,3 RS)-2-(2,4-difluorophenyl)-3-mercapto-1-(1H-1,2,4-triazol-1-yl)-2butanol (5.5 g) as colorless needles.

Workup

  1. temperaturerefluxed for 1 hour
  2. temperaturerefluxed for 2 hours
  3. temperatureAfter ice-cooling
  4. extractionextracted with methylene chloride (200 ml×2)
  5. dry with materialThe extract was dried over anhydrous sodium sulfate
  6. distillationdistilled off the solvent under reduced pressure
  7. washeluting with ethyl acetate-hexane (3:1)
  8. concentrationThe collected fractions of the object compound were concentrated
  9. additionethyl ether was added to the residue

Sources & evidence

ORD record
ord-f12c5fdbdcf344cfbdc165075fdb422c
Source dataset
uspto-grants-1995_02
Patent number
US05387599

Reaction notes

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