tert-Butylsulfinamide, (R)-(+)- → (R)-N-((3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)(4-fluorophenyl)methylene)-2-methylpropane-2-sulfinamide

HRID 238726Notes

Reaction equation

HRID 238726 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:15]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)=O)[CH:5]=[C:6]([O:8][C:9]([F:14])([F:13])[CH:10]([F:12])[F:11])[CH:7]=1.[CH3:24][C:25]([S@:28]([NH2:30])=[O:29])([CH3:27])[CH3:26]>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([C:15]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)=[N:30][S@@:28]([C:25]([CH3:27])([CH3:26])[CH3:24])=[O:29])[CH:5]=[C:6]([O:8][C:9]([F:14])([F:13])[CH:10]([F:12])[F:11])[CH:7]=1

Participants

4

Reactant 2

HCID 10964479tert-Butylsulfinamide, (R)-(+)-HCID 59458419(3-Fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)(4-fluorophenyl)methanone

Product 1

HCID 86613040(R)-N-((3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)(4-fluorophenyl)methylene)-2-methylpropane-2-sulfinamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(3-Fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)(4-fluorophenyl)methanone (3.3 g, 9.88 mmol) was stirred in anhydrous THF (20 mL) at r.t. under N2. (R)-(+)-2-Methylpropane-2-sulfinamide (1.21 g, 10 mmol, 1.01 eq) was added as one single portion, followed by addition of Ti(OEt)4 (3.09 mL, 14.91 mmol, 1.51 eq). The resulting solution was heated at reflux for 48 hours. The cooled mixture was evaporated. H2O (100 mL) was added, followed by the addition of EtOAc (100 mL). The mixture was filtered through celite, and washed with EtOAc (200 mL). The filtrate was washed with H2O and brine, dried over Na2SO4, filtered, and concentrated to dryness. The residue was purified by silica gel flash chromatography and was eluted with hexanes and EtOAc (0-30% EtOAc in hexanes) to give (R)—N-((3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)(4-fluorophenyl)methylene)-2-methylpropane-2-sulfinamide as yellowish viscous oil which solidified after drying under vacuum as light yellow solids (3.50 g, yield: 81.0%). LC-MS ESI 437.88 (M+H), retention time=3.83 min (10-90% MeOH in H2O with 0.1% TFA in a 4-min gradient); 1H NMR (400 MHz, CDCl3) δ ppm 7.82-6.99 (br, m, 7H), 5.90 (tt, J=52, 4 Hz, 1H), 1.31 (s, 9H).

Workup

  1. temperatureThe resulting solution was heated
  2. temperatureat reflux for 48 hours
  3. customThe cooled mixture was evaporated
  4. additionH2O (100 mL) was added
  5. additionfollowed by the addition of EtOAc (100 mL)
  6. filtrationThe mixture was filtered through celite
  7. washwashed with EtOAc (200 mL)
  8. washThe filtrate was washed with H2O and brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated to dryness
  12. customThe residue was purified by silica gel flash chromatography
  13. washwas eluted with hexanes and EtOAc (0-30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-3d399451790a428aa5360eaf48de1a04
Source dataset
uspto-grants-2014_02
Patent number
US08642576B2

Reaction notes

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