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

HRID 1712779

Reaction equation

HRID 1712779 reaction equation
[Si:1]([O:8][C:9]1[CH:10]=[C:11]([C:16]([C:18]2[CH:23]=[C:22]([O:24][C:25]([F:30])([F:29])[CH:26]([F:28])[F:27])[CH:21]=[C:20]([F:31])[CH:19]=2)=O)[CH:12]=[CH:13][C:14]=1[F:15])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH3:32][C:33]([S@:36]([NH2:38])=[O:37])([CH3:35])[CH3:34]>C1COCC1>[Si:1]([O:8][C:9]1[CH:10]=[C:11]([C:16]([C:18]2[CH:23]=[C:22]([O:24][C:25]([F:30])([F:29])[CH:26]([F:28])[F:27])[CH:21]=[C:20]([F:31])[CH:19]=2)=[N:38][S@@:36]([C:33]([CH3:35])([CH3:34])[CH3:32])=[O:37])[CH:12]=[CH:13][C:14]=1[F:15])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 10964479tert-Butylsulfinamide, (R)-(+)-HCID 59458571(3-(Tert-butyldimethylsilyloxy)-4-fluorophenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methanone

Product 1

HCID 86613059(R)-N-((3-(tert-butyldimethylsilyloxy)-4-fluorophenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methylene)-2-methylpropane-2-sulfinamideYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

A round bottom flask was charged with (3-(tert-butyldimethylsilyloxy)-4-fluorophenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methanone (2.09 g, 4.50 mmol), (R)-2-methylpropane-2-sulfinamide (653 mg, 5.4 mmol), Ti(OEt)4 (1.54 g, 6.76 mmol) and anhydrous THF (40 mL). The resulting solution was heated at 75° C. under argon for 14 h. The solvents were removed and the residue was diluted with ether (50 mL) and sat. NaCl (20 mL). The resulting mixture was filtered through a glass frit and the filtrate transferred to a separatory funnel. The organic portion was separated and the aqueous extracted with ether (2×20 mL). The combined organic portions were dried over Na2SO4, filtered and concentrated. The residue was dissolved in hexane:EtOAc and purified by ISCO chromatography (2×120 g column) using hexanes/EtOAc (0-100% over 30 min) to yield (R)—N-((3-(tert-butyldimethylsilyloxy)-4-fluorophenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methylene)-2-methylpropane-2-sulfinamide at a retention time of 14 min (2.05 g, 80% yield) LCMS: RT=2.37 min [M+H] 568.24 (Phenomenex Luna C18 column, 4.6×30 mm eluting with 10-90% MeOH/H2O over 2 minutes containing 0.1% TFA; 5 mL/min, monitoring at 220 nm). NMR: 400 MHz (CDCl3) 7.36 ppm, 1H, m; 7.11 ppm, 5H, m; 5.90 ppm, 1H, t, J=52.73 Hz; 0.97 ppm, 9H, s; 0.18 ppm, 6H, s.

Workup

  1. customThe solvents were removed
  2. additionthe residue was diluted with ether (50 mL) and sat. NaCl (20 mL)
  3. filtrationThe resulting mixture was filtered through a glass frit
  4. customthe filtrate transferred to a separatory funnel
  5. customThe organic portion was separated
  6. extractionthe aqueous extracted with ether (2×20 mL)
  7. dry with materialThe combined organic portions were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. dissolutionThe residue was dissolved in hexane
  11. customEtOAc and purified by ISCO chromatography (2×120 g column)
  12. customhexanes/EtOAc (0-100% over 30 min)

Sources & evidence

ORD record
ord-1056578a7d134b30b2f261038eef091e
Source dataset
uspto-grants-2010_09
Patent number
US07790770B2

Linked notes

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