Sodium hydride → 2-(2,5-Difluorophenyl)-2-[(1R)-1-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)ethyl]oxirane

HRID 379648Notes

Reaction equation

HRID 379648 reaction equation
[H-].[Na+].[I-].[CH3:4][S+](C)(C)=O.[F:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[C:17](=[O:27])[C@H:18]([O:20][CH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][O:22]1)[CH3:19]>CS(C)=O>[F:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[C:17]1([C@H:18]([O:20][CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][O:22]2)[CH3:19])[CH2:4][O:27]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 10199306(2R)-1-(2,5-Difluorophenyl)-2-((tetrahydro-2H-pyran-2-yl)oxy)propan-1-one

Product 1

HCID 98606092-(2,5-Difluorophenyl)-2-[(1R)-1-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)ethyl]oxiraneYield 97.1%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

To a stirred mixture of NaH (60% in oil, 9.1 g, 0.228 mol) in DMSO (300ml) was added portionwise trimethylsulfoxonium iodide (53.9 g, 0.245 mol ) at the inner temperature with the range from 15° C. to 18° C. over 20 min. The ice bath was removed and the mixture was stirred at r.t. for 3 hrs. The mixture was cooled down to 10° C. To this mixture was added a solution of (2R)-2′,5′-Difluoro-2-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)-propiophenone (47.3 g, 0.175 mol) in DMSO (150 ml) dropwise over 20 min. The resulting mixture was stirred at r.t. for 4 hrs. The reaction mixture was poured into ice-water (800 ml). The whole was extracted with EtOAc (400 ml+200 ml×2). The combined organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was chromatograkkphed on silicagel (n-hexane: EtOAc=8:1˜5:1) to give 2-(2,5-Difluorophenyl)-2-[(1R)-1-(3,4,5,6,-tetrahydro-2H-pyran-2-yloxy)ethyl]oxirane (48.3 g, 97% ).

Workup

  1. customThe ice bath was removed
  2. temperatureThe mixture was cooled down to 10° C
  3. stirringThe resulting mixture was stirred at r.t. for 4 hrs
  4. extractionThe whole was extracted with EtOAc (400 ml+200 ml×2)
  5. washThe combined organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ed15dba08a224b58b9690b502df9f704
Source dataset
uspto-grants-2001_10
Patent number
US06300353B1

Reaction notes

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