Cesium carbonate → (R)-1-(4-bromo-3-methyl-phenyl)-4-hydroxy-pyrrolidin-2-one

HRID 1754938Notes

Reaction equation

HRID 1754938 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][C:3]=1[CH3:9].[OH:10][C@H:11]1[CH2:15][NH:14][C:13](=[O:16])[CH2:12]1.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.C(=O)([O-])[O-].[Cs+].[Cs+]>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.C(Cl)(Cl)Cl.[Pd].[Pd].O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:14]2[CH2:15][C@H:11]([OH:10])[CH2:12][C:13]2=[O:16])=[CH:4][C:3]=1[CH3:9]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 185505(R)-(+)-4-Hydroxy-2-pyrrolidinoneHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27355742-Bromo-5-iodotoluene

Product 1

HCID 66816684(R)-1-(4-bromo-3-methyl-phenyl)-4-hydroxy-pyrrolidin-2-oneYield 38.1%

Reagents, catalysts & solvents 3

HCID 11029508Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 2-bromo-5-iodotoluene (500 mg, 1.68 mmol), (R)-4-hydroxy-pyrrolidinone (204 mg, 2.02 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (58.5 mg, 0.101 mmol), tris(dibenzylideneacetone)-dipalladium(0)-chloroform adduct (35.0 mg, 0.034 mmol) and cesium carbonate (769 mg, 2.36 mmol) in 1,4-dioxane (degassed, 5 ml) was stirred at 110° C. overnight in a nitrogen stream. The reaction mixture was treated with H2O and extracted with AcOEt (×2). The organic layers were combined and sequentially washed with H2O and saturated brine, and then dried over Na2SO4 and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (n-hexane/AcOEt) to give (R)-1-(4-bromo-3-methyl-phenyl)-4-hydroxy-pyrrolidin-2-one as a pale brown solid (173 mg, 38%).

Workup

  1. extractionextracted with AcOEt (×2)
  2. washsequentially washed with H2O and saturated brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified by silica gel chromatography (n-hexane/AcOEt)

Sources & evidence

ORD record
ord-83cc438b785f4e858558a55f309b7fb2
Source dataset
uspto-grants-2015_10
Patent number
US09169254B2

Reaction notes

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