tert-Butylsulfinamide, (S)-(-)- → (NE,S)-2-methyl-N-[2,2,2-trifluoro-1-[4-(6,6,6-trifluorohexoxy)phenyl]ethylidene]propane-2-sulfinamide

HRID 1629767Notes

Reaction equation

HRID 1629767 reaction equation
[F:1][C:2]([F:22])([F:21])[C:3]([C:5]1[CH:10]=[CH:9][C:8]([O:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][C:17]([F:20])([F:19])[F:18])=[CH:7][CH:6]=1)=O.[CH3:23][C:24]([S@@:27]([NH2:29])=[O:28])([CH3:26])[CH3:25]>C1COCC1.CCCCCC.CCOC(C)=O.C(O[Ti](OCC)(OCC)OCC)C>[CH3:23][C:24]([S@@:27](/[N:29]=[C:3](\[C:5]1[CH:10]=[CH:9][C:8]([O:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][C:17]([F:20])([F:19])[F:18])=[CH:7][CH:6]=1)/[C:2]([F:22])([F:21])[F:1])=[O:28])([CH3:26])[CH3:25]

Participants

7

Reactant 2

HCID 11355477tert-Butylsulfinamide, (S)-(-)-HCID 86685857HCID 86685857, compound

Product 1

HCID 89599581(NE,S)-2-methyl-N-[2,2,2-trifluoro-1-[4-(6,6,6-trifluorohexoxy)phenyl]ethylidene]propane-2-sulfinamideYield 66%

Reagents, catalysts & solvents 4

HCID 178477244HCID 178477244, compoundCatalystHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of Intermediate 8B (717 mg, 2.184 mmol) and (S)-2-methylpropane-2-sulfinamide (529 mg, 4.37 mmol) in THF (10 mL) was added tetraethoxytitanium (1993 mg, 8.74 mmol) in THF (20 mL). The resulting mixture was reflux for 5 h. TLC (20% EtOAc in hexane) indicated the starting ketone was completely consumed. The solvent was evaporated to afford a yellow oil. This yellow oil was dissolved in EtOAc and then washed with saturated NaHCO3 (25 mL) and a large amount of white precipitation formed which was removed by filtering through a bed of Celite®. The white precipitation was rinsed with EtOAc. The combined EtOAc solution was washed again with saturated NaHCO3, dried (MgSO4) and concentrated. The crude product was purified by silica gel chromatography (40 g silica gel, eluted with EtOAc in hexanes) to afford Intermediate 8C (620 mg, 66%).

Workup

  1. temperatureThe resulting mixture was reflux for 5 h
  2. customwas completely consumed
  3. customThe solvent was evaporated
  4. customto afford a yellow oil
  5. washwashed with saturated NaHCO3 (25 mL)
  6. customa large amount of white precipitation
  7. customformed which
  8. customwas removed
  9. filtrationby filtering through a bed of Celite®
  10. customThe white precipitation
  11. washwas rinsed with EtOAc
  12. washThe combined EtOAc solution was washed again with saturated NaHCO3
  13. dry with materialdried (MgSO4)
  14. concentrationconcentrated
  15. customThe crude product was purified by silica gel chromatography (40 g silica gel, eluted with EtOAc in hexanes)

Sources & evidence

ORD record
ord-8c3c0caf30f04112a83ad239e4f9cce8
Source dataset
uspto-grants-2014_07
Patent number
US08791091B2

Reaction notes

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