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

HRID 1993623Notes

Reaction equation

HRID 1993623 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[CH:15]=[C:14]([O:16][C:17]([F:22])([F:21])[CH:18]([F:20])[F:19])[CH:13]=[C:12]([F:23])[CH:11]=2)=O)=[CH:4][C:3]=1[O:24][CH3:25].[CH3:26][C:27]([S@:30]([NH2:32])=[O:31])([CH3:29])[CH3:28]>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[CH:15]=[C:14]([O:16][C:17]([F:22])([F:21])[CH:18]([F:20])[F:19])[CH:13]=[C:12]([F:23])[CH:11]=2)=[N:32][S@@:30]([C:27]([CH3:29])([CH3:28])[CH3:26])=[O:31])=[CH:4][C:3]=1[O:24][CH3:25]

Participants

4

Reactant 2

HCID 10964479tert-Butylsulfinamide, (R)-(+)-HCID 59134716(4-Fluoro-3-methoxyphenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methanone

Product 1

HCID 86612971(R)-N-((4-fluoro-3-methoxyphenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methylene)-2-methylpropane-2-sulfinamideYield 75%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (4-fluoro-3-methoxyphenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methanone (16 g, 43 mmol) in THF (70 mL) was added Ti(OEt)4 (15 g, 65.9 mmol), followed by the addition of (R)-2-methylpropane-2-sulfinamide (5.86 g, 48.3 mmol). The reaction mixture was heated at reflux for 16 h, allowed to cool to room temperature and quenched by addition of saturated NaCl. The resulting mixture was filtered and the organic solvent was removed under reduced pressure. The residue was purified by ISCO chromatography using hexanes/EtOAc (10-50%) to afford (R)-N-((4-fluoro-3-methoxyphenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methylene)-2-methylpropane-2-sulfinamide as an oil (15 g, 75%). LCMS: RT=4.01 min, [M+H] 468.1 (Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 4 minutes containing 0.1% TFA; 4 mL/min, monitoring at 220 nm).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 16 h
  3. customquenched by addition of saturated NaCl
  4. filtrationThe resulting mixture was filtered
  5. customthe organic solvent was removed under reduced pressure
  6. customThe residue was purified by ISCO chromatography

Sources & evidence

ORD record
ord-4e8772c4901b4e3b9ca75b5adf25b814
Source dataset
uspto-grants-2010_01
Patent number
US07652023B2

Reaction notes

Loading…