Potassium vinyltrifluoroborate → 1-t-Butyl 2-methyl (2S,4R)-4-{[(4-vinyl-1,3-dihydro-2H-isoindol-2-yl)carbonyl]oxy}pyrrolidine-1,2-dicarboxylate

HRID 388225Notes

Reaction equation

HRID 388225 reaction equation
Br[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][N:5]([C:11]([O:13][C@H:14]1[CH2:18][N:17]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[C@H:16]([C:26]([O:28][CH3:29])=[O:27])[CH2:15]1)=[O:12])[CH2:6]2.[CH:30]([B-](F)(F)F)=[CH2:31].[K+]>CCO.OS([O-])(=O)=O.[K+]>[CH:30]([C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][N:5]([C:11]([O:13][C@H:14]1[CH2:18][N:17]([C:19]([O:21][C:22]([CH3:24])([CH3:25])[CH3:23])=[O:20])[C@H:16]([C:26]([O:28][CH3:29])=[O:27])[CH2:15]1)=[O:12])[CH2:6]2)=[CH2:31]

Participants

5

Reactant 2

HCID 23679353Potassium vinyltrifluoroborateHCID 534655661-(1,1-Dimethylethyl) 2-methyl (2S,4R)-4-(((4-bromo-1,3-dihydro-2H-isoindol-2-yl)carbonyl)oxy)-1,2-pyrrolidinedicarboxylate

Product 1

HCID 453783721-t-Butyl 2-methyl (2S,4R)-4-{[(4-vinyl-1,3-dihydro-2H-isoindol-2-yl)carbonyl]oxy}pyrrolidine-1,2-dicarboxylate

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 516920Potassium bisulfateSolvent

Procedure

To a solution of 1-t-butyl 2-methyl (2S,4R)-4-{[(4-bromo-1,3-dihydro-2H-isoindol-2-yl)carbonyl]oxy}pyrrolidine-1,2-dicarboxylate (10.0 g, 21.3 mmol) in EtOH (200 mL) was added potassium vinyltrifluoroborate (4.28 g, 32 mmol) and Et3OH (4.5 mL, 32 mmol) followed by dichloro[1,1-bis(diphenylphosphino)ferrocene]palladium (II) chloride dichloromethane adduct (175 mg, 0.21 mmol). The reaction mixture was heated to reflux for 6 hours, cooled to RT, diluted with 10% aqueous KHSO4. The EtOH was removed by evaporation in vacuo. The aqueous residue was extracted with EtOAc, and the organic phase washed with brine, dried over Na2SO4. The solvent was evaporated, and the crude product was purified by chromatography on silica eluting with 40-60% EtOAc/hexane to give, after evaporation, the title compound (8.18 g). LRMS (ESI) m/z 417.2 [(M+H)+; calcd for C22H29N2O6: 417.2].

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 6 hours
  3. customThe EtOH was removed by evaporation in vacuo
  4. extractionThe aqueous residue was extracted with EtOAc
  5. washthe organic phase washed with brine
  6. dry with materialdried over Na2SO4
  7. customThe solvent was evaporated
  8. customthe crude product was purified by chromatography on silica eluting with 40-60% EtOAc/hexane
  9. customto give
  10. customafter evaporation

Sources & evidence

ORD record
ord-7c911949435d4d8d83d30d6c387581fb
Source dataset
uspto-grants-2013_02
Patent number
US08377873B2

Reaction notes

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