tert-Butylsulfinamide, (R)-(+)- → (NZ,R)-N-[1-(5-bromo-2-fluorophenyl)-2-fluoroethylidene]-2-methylpropane-2-sulfinamide

HRID 627636Notes

Reaction equation

HRID 627636 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:12])=[C:6]([C:8](=O)[CH2:9][F:10])[CH:7]=1.[CH3:13][C:14]([S@:17]([NH2:19])=[O:18])([CH3:16])[CH3:15].O.CCOC(C)=O>O1CCCC1.[O-]CC.[Ti+4].[O-]CC.[O-]CC.[O-]CC>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:12])=[C:6](/[C:8](=[N:19]/[S@@:17]([C:14]([CH3:16])([CH3:15])[CH3:13])=[O:18])/[CH2:9][F:10])[CH:7]=1

Participants

6

Reactant 3

HCID 10964479tert-Butylsulfinamide, (R)-(+)-HCID 22728543Water ethylacetateHCID 867157171-(5-Bromo-2-fluorophenyl)-2-fluoroethanone

Product 1

HCID 90301236(NZ,R)-N-[1-(5-bromo-2-fluorophenyl)-2-fluoroethylidene]-2-methylpropane-2-sulfinamideYield 85%

Reagents, catalysts & solvents 2

HCID 76524Titanium tetraethoxideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Titanium (IV) ethoxide (4.05 mL, 19.6 mmol) was added via syringe to a solution of 1-(5-bromo-2-fluorophenyl)-2-fluoroethanone (2.3 g, 9.79 mmol) and (R)-(+)-2-methyl-2-propanesulfinamide (2.37 g, 19.57 mmol) in tetrahydrofuran (20 ml) at RT. The reaction was stirred for 18 hours and then the reaction was slowly poured into a vigorously stirred water/EtOAc mixture. After stirring 15 minutes, the mixture was filtered through a Celite pad, which was rinsed with ethyl acetate, and the phases were separated. The aqueous layer was extracted with ethyl acetate; the combined organic extracts were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by silica-gel chromatography, eluting with 10% EtOAc in hexanes, to provide the title compound (2.81 g, 8.31 mmol, 85% yield) as a yellow oil. LC/MS (ESI+) m/z=338, 340 (M+H; 2 bromine isotopes).

Workup

  1. stirringAfter stirring 15 minutes
  2. filtrationthe mixture was filtered through a Celite pad, which
  3. washwas rinsed with ethyl acetate
  4. customthe phases were separated
  5. extractionThe aqueous layer was extracted with ethyl acetate
  6. washthe combined organic extracts were washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by silica-gel chromatography
  11. washeluting with 10% EtOAc in hexanes

Sources & evidence

ORD record
ord-099aed5539964d5aa9b77e0bbc77048c
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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