Triethylamine → 1-(((2R,3S)-2-(2,5-difluorophenyl)-3-methyloxiran-2-yl)methyl)-1H-1,2,4-triazole

HRID 379666Notes

Reaction equation

HRID 379666 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C@:9]([OH:19])([C@H:16](O)[CH3:17])[CH2:10][N:11]1[CH:15]=[N:14][CH:13]=[N:12]1.CCN(CC)CC.CS(Cl)(=O)=O.C[O-].[Na+]>C(Cl)Cl.CCOC(C)=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C@@:9]1([CH2:10][N:11]2[CH:15]=[N:14][CH:13]=[N:12]2)[C@H:16]([CH3:17])[O:19]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 10942334Sodium MethoxideHCID 54455778(2R,3R)-2-(2,5-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butane-2,3-diol

Product 1

HCID 101311921-(((2R,3S)-2-(2,5-difluorophenyl)-3-methyloxiran-2-yl)methyl)-1H-1,2,4-triazoleYield 88%

Reagents, catalysts & solvents 1

HCID 21226138Dichloromethane ethylacetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (2R,3R)-2-(2,5-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2,3-butanediol (53.0 g, 197 mmol) and Et3N (54.8 mL, 394 mmol) in CH2Cl2-EtOAc (1:3, 400 mL) cooled in an ice-bath was added MsCl (17.5 mL, 227 mmol) dropwise over a period of 15 min. After stirring for 30 min at 0° C., the mixture was warmed to room temperature and quenched with water (200 mL). EtOAc (200 mL) was added and the organic layer was washed with water and brine, dried over MgSO4 and evaporated under reduced pressure. The obtaining residue was dissolved in MeOH (500 mL) and cooled in an ice-bath. A solution of NaOMe (41.8 g, 28% in MeOH, 217 mmol) was added dropwise and after the completion of the addition, the mixture was stirred for 15 min at 0° C. MeOH was evaporated under reduced pressure and the resulting residue was dissolved in EtOAc (500 mL). The EtOAc solution was washed with water and brine, dried over MgSO4 and evaporated under reduced pressure. The obtaining solid was recrystalized from t-BuOMe-hexane to give pure (2R,3S)-2-(2,5-Difluorophenyl)-3-methyl-2-[(1H-1,2,4-triazol-1-yl)-methyl]-oxirane (43.5 g, 88%).

Workup

  1. temperaturethe mixture was warmed to room temperature
  2. customquenched with water (200 mL)
  3. additionEtOAc (200 mL) was added
  4. washthe organic layer was washed with water and brine
  5. dry with materialdried over MgSO4
  6. customevaporated under reduced pressure
  7. dissolutionThe obtaining residue was dissolved in MeOH (500 mL)
  8. temperaturecooled in an ice-bath
  9. additionafter the completion of the addition
  10. stirringthe mixture was stirred for 15 min at 0° C
  11. customMeOH was evaporated under reduced pressure
  12. dissolutionthe resulting residue was dissolved in EtOAc (500 mL)
  13. washThe EtOAc solution was washed with water and brine
  14. dry with materialdried over MgSO4
  15. customevaporated under reduced pressure
  16. customThe obtaining solid was recrystalized from t-BuOMe-hexane

Sources & evidence

ORD record
ord-25bcd3e528f8408cad77bf7c9ea3a679
Source dataset
uspto-grants-2001_10
Patent number
US06300353B1

Reaction notes

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