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 920166노트

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HRID 920166 반응식
[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

참가 물질

5

반응물 3

HCID 87949Lawesson's reagent3회HCID 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

생성물 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-thione수율 71.4%

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

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온도
80 °C

실험 절차

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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-a818999a138f44e4be630b200d202cbf
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09273042B2

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