tert-Butylsulfinamide, (R)-(+)- → (NE,R)-N-[1-(6-bromo-3-fluoro-4-triethylsilylpyridin-2-yl)-2,2-difluoroethylidene]-2-methylpropane-2-sulfinamide

HRID 930353

Reaction equation

HRID 930353 reaction equation
[Br:1][C:2]1[N:7]=[C:6]([C:8](=O)[CH:9]([F:11])[F:10])[C:5]([F:13])=[C:4]([Si:14]([CH2:19][CH3:20])([CH2:17][CH3:18])[CH2:15][CH3:16])[CH:3]=1.[CH3:21][C:22]([S@:25]([NH2:27])=[O:26])([CH3:24])[CH3:23]>C1COCC1.C(O[Ti](OCC)(OCC)OCC)C>[Br:1][C:2]1[N:7]=[C:6](/[C:8](=[N:27]\[S@@:25]([C:22]([CH3:24])([CH3:23])[CH3:21])=[O:26])/[CH:9]([F:11])[F:10])[C:5]([F:13])=[C:4]([Si:14]([CH2:19][CH3:20])([CH2:17][CH3:18])[CH2:15][CH3:16])[CH:3]=1

Participants

5

Reactant 2

HCID 10964479tert-Butylsulfinamide, (R)-(+)-HCID 866680831-(6-Bromo-3-fluoro-4-(triethylsilyl)pyridin-2-yl)-2,2-difluoroethanone

Product 1

HCID 90373072(NE,R)-N-[1-(6-bromo-3-fluoro-4-triethylsilylpyridin-2-yl)-2,2-difluoroethylidene]-2-methylpropane-2-sulfinamideYield 56.4%

Reagents, catalysts & solvents 2

HCID 178477244HCID 178477244, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 1-(6-bromo-3-fluoro-4-(triethylsilyl)pyridin-2-yl)-2,2-difluoroethanone (0.666 g, 1.808 mmol), (R)-2-methylpropane-2-sulfinamide (0.219 g, 1.808 mmol) and tetraethoxytitanium (0.758 ml, 3.62 mmol) in THF (4.52 ml) in a sealed microwave vial was stirred at 80° C. for 3 h. After cooling to RT, the reaction mixture was poured into an ice-cold saturated NaCl solution, stirred for 10 min, and the precipitate was filtered through a pad of celite and washed with EtOAc. The aqueous layer was back extracted with EtOAc (2×) and the combined EtOAc layers were dried (MgSO4) and concentrated. The crude material was purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 0% to 30% EtOAc in hexane, to provide (R,E)-N-(1-(6-bromo-3-fluoro-4-(triethylsilyl)pyridin-2-yl)-2,2-difluoroethylidene)-2-methylpropane-2-sulfinamide (0.481 g, 1.020 mmol, 56.4% yield) as dark-brown oil.

Workup

  1. temperatureAfter cooling to RT
  2. stirringstirred for 10 min
  3. filtrationthe precipitate was filtered through a pad of celite
  4. washwashed with EtOAc
  5. extractionThe aqueous layer was back extracted with EtOAc (2×)
  6. dry with materialthe combined EtOAc layers were dried (MgSO4)
  7. concentrationconcentrated
  8. customThe crude material was purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g)
  9. washeluting with a gradient of 0% to 30% EtOAc in hexane

Sources & evidence

ORD record
ord-e979165153a44e79b914a6f7c7a35d56
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Linked notes

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