Sulfoxonium, trimethyl-, iodide (1:1) → 4-((6-((2-(2,4-Difluorophenyl)oxiran-2-yl)difluoromethyl)pyridin-3-yl)oxy)benzonitrile

HRID 63255Notes

Reaction equation

HRID 63255 reaction equation
[I-].C[S+](C)(C)=O.[CH3:7]C(C)([O-])C.[K+].[F:13][C:14]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=1[C:21](=[O:40])[C:22]([C:25]1[N:30]=[CH:29][C:28]([O:31][C:32]2[CH:39]=[CH:38][C:35]([C:36]#[N:37])=[CH:34][CH:33]=2)=[CH:27][CH:26]=1)([F:24])[F:23].C(=O)(O)[O-].[Na+]>C1COCC1.CS(C)=O.C1COCC1.[Cl-].[Na+].O>[F:13][C:14]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=1[C:21]1([C:22]([F:23])([F:24])[C:25]2[N:30]=[CH:29][C:28]([O:31][C:32]3[CH:39]=[CH:38][C:35]([C:36]#[N:37])=[CH:34][CH:33]=3)=[CH:27][CH:26]=2)[CH2:7][O:40]1

Participants

8

Reactant 4

HCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 516892Sodium BicarbonateHCID 23665647Potassium tert-butoxideHCID 900521254-((6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-oxoethyl)pyridin-3-yl)oxy)benzonitrile

Product 1

HCID 893090844-((6-((2-(2,4-Difluorophenyl)oxiran-2-yl)difluoromethyl)pyridin-3-yl)oxy)benzonitrileYield 44.2%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 21830753dimethylsulfoxide THFSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a magnetically stirred solution of trimethylsulfoxonium iodide (6.4 g, 29.42 mmol) in dry THF/DMSO (10:6) was added potassium tert-butoxide (3.302 g, 29.42 mmol) under a N2 atmosphere. The reaction mixture was stirred at room temperature for 1 h and then cooled to 0° C. 4-((6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2oxoethyl)pyridin-3-yl)oxy)benzonitrile (8.737 g, 22.63 mmol) in THF (40 mL) was added slowly to maintain the temperature below 5° C. The reaction mixture was maintained at 0° C. for 30 min and saturated sodium bicarbonate was added to quench the reaction. Brine was added and the mixture was extracted with Et2O. The combined organic phases were diluted with hexanes and washed with brine and water, dried (Na2SO4) and concentrated to give the title compound as an amber oil (4 g, 44%): 1H NMR (300 MHz, CDCl3) δ 8.46 (d, J=2.7 Hz, 1H), 7.73-7.62 (m, 2H), 7.52 (dd, J=8.6, 0.6 Hz, 1H), 7.48-7.35 (m, 2H), 7.13-7.02 (m, 2H), 6.92-6.80 (m, 1H), 6.75 (ddd, J=10.0, 8.9, 2.5 Hz, 1H), 3.46 (d, J=5.1 Hz, 1H), 3.03-2.96 (m, 1H); ESIMS m/z 401 ([M+H]+).

Workup

  1. temperaturecooled to 0° C
  2. temperatureto maintain the temperature below 5° C
  3. temperatureThe reaction mixture was maintained at 0° C. for 30 min
  4. customto quench
  5. customthe reaction
  6. extractionthe mixture was extracted with Et2O
  7. additionThe combined organic phases were diluted with hexanes
  8. washwashed with brine and water
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-c5f5dc856edd4224bf4a0766c3a10b1f
Source dataset
uspto-grants-2016_09
Patent number
US09447073B2

Reaction notes

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