Cesium carbonate → 4-[(2S,3S)-2-ethyl-3-hydroxy-5-oxopyrrolidin-1-yl]-2-methoxybenzonitrile

HRID 1173733Notes

Reaction equation

HRID 1173733 reaction equation
[Si]([O:8][C@@H:9]1[C@H:13]([CH2:14][CH3:15])[NH:12][C:11](=[O:16])[CH2:10]1)(C(C)(C)C)(C)C.I[C:18]1[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[C:20]([O:26][CH3:27])[CH:19]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[CH2:14]([C@H:13]1[C@@H:9]([OH:8])[CH2:10][C:11](=[O:16])[N:12]1[C:18]1[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[C:20]([O:26][CH3:27])[CH:19]=1)[CH3:15]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 508791924-Iodo-2-methoxybenzonitrileHCID 67105254(4S,5S)-4-(tert-butyldimethylsilyloxy)-5-ethylpyrrolidin-2-one

Product 1

HCID 595569094-[(2S,3S)-2-ethyl-3-hydroxy-5-oxopyrrolidin-1-yl]-2-methoxybenzonitrileYield 32%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of (4S,5S)-4-(tert-butyldimethylsilyloxy)-5-ethylpyrrolidin-2-one (340 m), 4-iodo-2-methoxybenzonitrile (434 mg), cesium carbonate (683 mg), tris(dibenzylideneacetone)dipalladium(0) (64.0 mg) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (121 mg) in dioxane (10 mL) was stirred at 80° C. for 6.5 hr under an argon atmosphere. After allowing to room temperature, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (eluent: hexane-ethyl acetate=99:1→1:1). The obtained residue was dissolved in ethanol (10 mL)-tetrahydrofuran (10 mL), 6 mol/L hydrochloric acid (4.66 mL) was added, and the mixture was stirred overnight at room temperature. The mixture was neutralized with saturated aqueous sodium hydrogen carbonate solution under ice-cooling, and extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent: hexane:ethyl acetate=9:1→1:9), and recrystallized from tetrahydrofuran-hexane to give the title compound as colorless crystals (yield: 115 mg, 32%).

Workup

  1. customAfter allowing to room temperature
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe extract was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by basic silica gel column chromatography (eluent: hexane-ethyl acetate=99:1→1:1)
  7. dissolutionThe obtained residue was dissolved in ethanol (10 mL)-tetrahydrofuran (10 mL), 6 mol/L hydrochloric acid (4.66 mL)
  8. additionwas added
  9. temperaturecooling
  10. extractionextracted with ethyl acetate
  11. washThe organic layer was washed with saturated brine
  12. dry with materialdried over magnesium sulfate
  13. customthe solvent was evaporated under reduced pressure
  14. customThe obtained residue was purified by silica gel column chromatography (eluent: hexane:ethyl acetate=9:1→1:9)
  15. customrecrystallized from tetrahydrofuran-hexane

Sources & evidence

ORD record
ord-03a2a6db92c14a259638418353f07525
Source dataset
uspto-grants-2010_11
Patent number
US07834051B2

Reaction notes

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