1,4-Dibromobenzene → tert-Butyl N-[(3R)-1-(4-bromophenyl)-5-oxopyrrolidin-3-yl]carbamate

HRID 715922Notes

Reaction equation

HRID 715922 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][CH:3]=1.[O:9]=[C:10]1[NH:14][CH2:13][C@H:12]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:11]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+]>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.ClCCl.O1CCOCC1>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([N:14]2[C:10](=[O:9])[CH2:11][C@@H:12]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:20])([CH3:19])[CH3:21])[CH2:13]2)=[CH:3][CH:4]=1

Participants

9

Reactant 4

HCID 78041,4-DibromobenzeneHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 71301758tert-Butyl [(3R)-5-oxopyrrolidin-3-yl]carbamate

Product 1

HCID 117893470tert-Butyl N-[(3R)-1-(4-bromophenyl)-5-oxopyrrolidin-3-yl]carbamateYield 13.5%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

1,4-Dioxane (8 ml) was added to 1,4-dibromobenzene (176 mg), t-butyl N-[(3R)-5-oxopyrrolidin-3-yl]carbamate (100 mg), tris(dibenzylideneacetone)dipalladium(0) (23 mg), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (29 mg), and cesium carbonate (244 mg), and the mixture was stirred at 90° C. for 1 hour under an argon atmosphere and then further heated to reflux for 1 hour. Dichloromethane and water were added to the reaction solution to separate the aqueous and organic layers. The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (n-hexane-ethyl acetate) to obtain the title compound (24 mg).

Workup

  1. temperaturefurther heated
  2. temperatureto reflux for 1 hour
  3. customto separate the aqueous and organic layers
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (n-hexane-ethyl acetate)

Sources & evidence

ORD record
ord-47fa6811a9804c93a19622c178700d70
Source dataset
uspto-grants-2015_11
Patent number
US09187489B2

Reaction notes

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