Lawesson's reagent → (R)-8-(5-bromo-2-fluoro-phenyl)-8-methyl-6,6-dioxo-6lambda6-thia-9-aza-spiro[4.5]dec-2-en-10-thione

HRID 920166Notes

Reaction equation

HRID 920166 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:22])=[C:6]([C@@:8]2([CH3:21])[NH:17][C:16](=O)[C:11]3([CH2:15][CH:14]=[CH:13][CH2:12]3)[S:10](=[O:20])(=[O:19])[CH2:9]2)[CH:7]=1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:32])=CC=1.C([O-])(O)=O.[Na+]>O1CCOCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:22])=[C:6]([C@@:8]2([CH3:21])[NH:17][C:16](=[S:32])[C:11]3([CH2:15][CH:14]=[CH:13][CH2:12]3)[S:10](=[O:20])(=[O:19])[CH2:9]2)[CH:7]=1

Participants

5

Reactant 3

HCID 87949Lawesson's reagent3×HCID 516892Sodium BicarbonateHCID 90025282(R)-8-(5-bromo-2-fluoro-phenyl)-8-methyl-6,6-dioxo-6lambda6-thia-9-aza-spiro[4.5]dec-2-en-10-one

Product 1

HCID 90025491(R)-8-(5-bromo-2-fluoro-phenyl)-8-methyl-6,6-dioxo-6lambda6-thia-9-aza-spiro[4.5]dec-2-en-10-thioneYield 71.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of (R)-8-(5-bromo-2-fluoro-phenyl)-8-methyl-6,6-dioxo-6λ6-thia-9-aza-spiro[4.5]dec-2-en-10-one (410 mg, 1.06 mmol, Eq: 1.00) and Lawesson's reagent (427 mg, 1.06 mmol, Eq: 1.00) in dioxane (10 ml) was stirred at 80° C. for 2 hours. More Lawesson's reagent (427 mg, 1.06 mmol, Eq: 1.00) was added and stirring continued at 85° C. for 16 hours. More Lawesson's reagent (427 mg, 1.06 mmol, Eq: 1.00) was added and stirring continued at 95° C. for 6 hours. The reaction mixture was poured into sat. NaHCO3-solution and extracted twice with ethyl acetate. The organic layers were washed with brine, dried over Na2SO4, filtered and evaporated to give light yellow oil. The residue was chromatographed on 20 g silica gel with dichloromethane/heptane to give (R)-8-(5-bromo-2-fluoro-phenyl)-8-methyl-6,6-dioxo-6λ6-thia-9-aza-spiro[4.5]dec-2-en-10-thione (305 mg, 754 μmol, 71.4% yield) as a light yellow foam. MS (ISP): m/z=404.1 [M+H]+ and 406.2 [M+2+H]+.

Workup

  1. stirringstirring
  2. waitcontinued at 85° C. for 16 hours
  3. stirringstirring
  4. waitcontinued at 95° C. for 6 hours
  5. extractionextracted twice with ethyl acetate
  6. washThe organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customevaporated
  10. customto give light yellow oil
  11. customThe residue was chromatographed on 20 g silica gel with dichloromethane/heptane

Sources & evidence

ORD record
ord-a818999a138f44e4be630b200d202cbf
Source dataset
uspto-grants-2016_03
Patent number
US09273042B2

Reaction notes

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