Triacetoxyperiodinane → (R)-N-((S)-2-(6-bromo-3-fluoropyridin-2-yl)-1,1-difluoro-4-oxobutan-2-yl)-2-methylpropane-2-sulfinamide

HRID 930357Notes

Reaction equation

HRID 930357 reaction equation
[Br:1][C:2]1[N:7]=[C:6]([C@:8]([NH:15][S@@:16]([C:18]([CH3:21])([CH3:20])[CH3:19])=[O:17])([CH2:12][CH2:13][OH:14])[CH:9]([F:11])[F:10])[C:5]([F:22])=[CH:4][CH:3]=1.BrC1N=C([C@@](N[S@@](C(C)(C)C)=O)(CCO)C(F)F)C(F)=CC=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.BrC1N=C([C@](N[S@@](C(C)(C)C)=O)(CC=O)C(F)F)C(F)=CC=1>C(Cl)Cl.O>[Br:1][C:2]1[N:7]=[C:6]([C@@:8]([NH:15][S@@:16]([C:18]([CH3:20])([CH3:19])[CH3:21])=[O:17])([CH2:12][CH:13]=[O:14])[CH:9]([F:11])[F:10])[C:5]([F:22])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 159087TriacetoxyperiodinaneHCID 86732175(R)-N-((S)-2-(6-bromo-3-fluoropyridin-2-yl)-1,1-difluoro-4-hydroxybutan-2-yl)-2-methylpropane-2-sulfinamideHCID 86732176(R)-N-((R)-2-(6-bromo-3-fluoropyridin-2-yl)-1,1-difluoro-4-hydroxybutan-2-yl)-2-methylpropane-2-sulfinamideHCID 86732178(R)-N-((R)-2-(6-bromo-3-fluoropyridin-2-yl)-1,1-difluoro-4-oxobutan-2-yl)-2-methylpropane-2-sulfinamide

Product 1

HCID 86732177(R)-N-((S)-2-(6-bromo-3-fluoropyridin-2-yl)-1,1-difluoro-4-oxobutan-2-yl)-2-methylpropane-2-sulfinamideYield 70.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of the mixture of (R)-N-((R)-2-(6-bromo-3-fluoropyridin-2-yl)-1,1-difluoro-4-hydroxybutan-2-yl)-2-methylpropane-2-sulfinamide and (R)-N-((S)-2-(6-bromo-3-fluoropyridin-2-yl)-1,1-difluoro-4-hydroxybutan-2-yl)-2-methylpropane-2-sulfinamide (0.17 g, 0.422 mmol) in DCM (2.1 ml) was added Dess-Martin periodinane (0.215 g, 0.506 mmol). The reaction mixture was stirred at RT. After 1 h, the mixture was diluted with water and extracted with DCM three times. The organic layer was washed with brine, dried over Na2SO4, and concentrated in vacuo. The crude was purified by silica gel chromatography: 40 g Grace column, 0-50% EtOAc-hexane in 20 min to give a 3:1 mixture of (R)-N-((R)-2-(6-bromo-3-fluoropyridin-2-yl)-1,1-difluoro-4-oxobutan-2-yl)-2-methylpropane-2-sulfinamide and (R)-N-((S)-2-(6-bromo-3-fluoropyridin-2-yl)-1,1-difluoro-4-oxobutan-2-yl)-2-methylpropane-2-sulfinamide (0.12 g, 0.299 mmol, 70.9% yield) was obtained as a colorless oil. MS m/z=401, 403 M+, Calculated for C13H16BrF3N2O2S: 401.24. Used directly in the following step.

Workup

  1. extractionextracted with DCM three times
  2. washThe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe crude was purified by silica gel chromatography
  6. custom40 g Grace column, 0-50% EtOAc-hexane in 20 min to give

Sources & evidence

ORD record
ord-218f62e306ae42ec8df907bcbaff4743
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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