Hydrochloric Acid → 1-((2-(2,4-Difluorophenyl)-3-methyloxiran-2-yl)methyl)-1H-1,2,4-triazole, (2R-cis)-

HRID 2099895Notes

Reaction equation

HRID 2099895 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@:9]1(O[CH2:17]1)[C@H:10](OS(C)(=O)=O)[CH3:11].[NH:19]1[CH:23]=[N:22][CH:21]=[N:20]1.[OH-:24].[Na+].Cl>CN(C=O)C.C1(C)C=CC=CC=1>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@:9]1([CH2:17][N:19]2[CH:23]=[N:22][CH:21]=[N:20]2)[C@H:10]([CH3:11])[O:24]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 92571H-1,2,4-TriazoleHCID 14798Sodium HydroxideHCID 11680698HCID 11680698, compound

Product 1

HCID 101311911-((2-(2,4-Difluorophenyl)-3-methyloxiran-2-yl)methyl)-1H-1,2,4-triazole, (2R-cis)-Yield 36%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

In DMF (130 ml), (2R,3R)-3-(2,4-difluorophenyl)-3,4-epoxy-2-methanesulfonyloxybutane (82.8 g, 0.3 mol) and 1,2,4-triazole (26.7 g, 0.39 mol) were dissolved and heated to about 60° C. with stirring. 20% aqueous sodium hydroxide solution (103.8 g, 0.37 mol) was dropped thereto over about 1.5 hours and further stirred for 7 hours at the same temperature for the reaction. After the reaction, the mixture was cooled and toluene (150 ml) was added thereto. The obtained mixture was neutralized (pH 7-8) with 35% hydrochloric acid and subjected to phase separation. The water layer was extracted with toluene (150 ml) three times. The combined toluene layer was washed with diluted hydrochloric acid, aqueous sodium hydrogen carbonate solution and water subsequently, and the solvent was distilled off under a reduced pressure. The concentrated residue was subjected to recrystallization from a mixed solvent of toluene/heptane (20/80; v/v, 400 ml) to give (2R,3S)-2-(2,4-difluorophenyl)-3-methyl-2-[(1H-1,2,4-triazol-1-yl)methyl]oxirane (27.1 g, yield 36.0%, optical purity (HPLC condition-1) 100% e.e., mp 89° C.).

Workup

  1. stirringfurther stirred for 7 hours at the same temperature for the reaction
  2. customAfter the reaction
  3. temperaturethe mixture was cooled
  4. customsubjected to phase separation
  5. extractionThe water layer was extracted with toluene (150 ml) three times
  6. washThe combined toluene layer was washed with diluted hydrochloric acid, aqueous sodium hydrogen carbonate solution and water subsequently
  7. distillationthe solvent was distilled off under a reduced pressure
  8. customThe concentrated residue was subjected to recrystallization from a mixed solvent of toluene/heptane (20/80; v/v, 400 ml)

Sources & evidence

ORD record
ord-a5903c172d0344a1aed3f1528c0345db
Source dataset
uspto-grants-2009_08
Patent number
US07569699B2

Reaction notes

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