Cesium carbonate → 4-[(2S,3S)-3-(tert-butyldimethylsilyloxy)-2-methyl-5-oxopyrrolidin-1-yl]-2-fluoro-3-methylbenzonitrile

HRID 1173547Notes

Reaction equation

HRID 1173547 reaction equation
Br[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([F:10])[C:3]=1[CH3:11].[Si:12]([O:19][C@@H:20]1[C@H:24]([CH3:25])[NH:23][C:22](=[O:26])[CH2:21]1)([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13].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>[Si:12]([O:19][C@H:20]1[CH2:21][C:22](=[O:26])[N:23]([C:2]2[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([F:10])[C:3]=2[CH3:11])[C@H:24]1[CH3:25])([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 595569134-Bromo-2-fluoro-3-methylbenzonitrileHCID 59556992HCID 59556992, compound

Product 1

HCID 595569304-[(2S,3S)-3-(tert-butyldimethylsilyloxy)-2-methyl-5-oxopyrrolidin-1-yl]-2-fluoro-3-methylbenzonitrileYield 19%

Reagents, catalysts & solvents 3

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

Procedure

To a solution of 4-bromo-2-fluoro-3-methylbenzonitrile (1.10 g), (4S,5S)-4-(tert-butyldimethylsilyloxy)-5-methylpyrrolidin-2-one (1.18 g), cesium carbonate (2.51 g), tris(dibenzylideneacetone)dipalladium(0) (235 mg) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (297 mg) in dioxane (30 mL) was stirred under an argon atmosphere at 80° C. for 8 hr. 5 The reaction mixture was added to water, 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 silica gel column chromatography to give the title compound as a colorless solid (yield: 347 mg, 19%).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-3413c2f92c2945588a66af11c12a5fd8
Source dataset
uspto-grants-2010_11
Patent number
US07834051B2

Reaction notes

Loading…