1,4-Dibromobenzene → (S)-3-(4-bromophenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one

HRID 525316Notes

Reaction equation

HRID 525316 reaction equation
[CH3:1][C:2]1([CH3:14])[O:6][C:5](=[O:7])[NH:4][C@H:3]1[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[Br:15][C:16]1[CH:21]=[CH:20][C:19](Br)=[CH:18][CH:17]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CNCCNC>[Cu]I.O.O1CCOCC1>[Br:15][C:16]1[CH:21]=[CH:20][C:19]([N:4]2[C@@H:3]([C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=3)[C:2]([CH3:14])([CH3:1])[O:6][C:5]2=[O:7])=[CH:18][CH:17]=1

Participants

8

Reactant 4

HCID 78041,4-DibromobenzeneHCID 8070N,N'-DimethylethylenediamineHCID 62657Potassium Phosphate, TribasicHCID 2733820(S)-(+)-5,5-Dimethyl-4-phenyl-2-oxazolidinone

Product 1

HCID 89814002(S)-3-(4-bromophenyl)-5,5-dimethyl-4-phenyloxazolidin-2-oneYield 51.1%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a round bottom flask were added (S)-5,5-dimethyl-4-phenyloxazolidin-2-one (2.00 g, 10.46 mmol)(commercially available from Sigma-Aldrich, Milwaukee, Wis.), 1,4-dibromobenzene (commercially available from Sigma-Aldrich, Milwaukee, Wis.) (4.93 g), 1,4-dioxane (41.8 mL) and tribasic potassium phosphate (11.10 g, 52.3 mmol). The vessel was purged with nitrogen and then N,N′-dimethylethylenediamine (2.251 mL, 20.92 mmol) and copper (I) iodide (1.992 g, 10.46 mmol) were added. The vessel was heated at reflux overnight providing an orange suspension containing product along with two other major impurities according to LC-MS. To the mixture was added water, and the resulting slurry was transferred to a separatory funnel and extracted with EtOAc (2×). The combined organic layers were back extracted with water, separated, dried with Na2SO4, filtered, and dried under reduced pressure. The residue was purified twice using a 50 g SNAP column ramping EtOAc in heptane from 0-30% leading to coelution of product with impurity. Another run using DCM:MeOH:NH4OH (90:10:1) in DCM afforded (S)-3-(4-bromophenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one (1.85 g, 5.34 mmol, 51.1% yield) as a white solid. Minor amounts of (S)-5,5-dimethyl-4-phenyloxazolidin-2-one was still present after the second purification, but the material was used as is. 1H NMR (400 MHz, DMSO-d6) δ=7.50-7.41 (m, 4H), 7.40-7.34 (m, 2H), 7.33-7.28 (m, 2H), 7.26-7.20 (m, 1H), 5.46 (s, 1H), 1.62 (s, 3H), 0.89 (s, 3H).

Workup

  1. customThe vessel was purged with nitrogen
  2. temperatureThe vessel was heated
  3. temperatureat reflux overnight
  4. customproviding an orange suspension
  5. additioncontaining product along with two other major impurities
  6. customthe resulting slurry was transferred to a separatory funnel
  7. extractionextracted with EtOAc (2×)
  8. extractionThe combined organic layers were back extracted with water
  9. customseparated
  10. dry with materialdried with Na2SO4
  11. filtrationfiltered
  12. customdried under reduced pressure
  13. customThe residue was purified twice

Sources & evidence

ORD record
ord-e7d67bf6450b4d69b06880facb634728
Source dataset
uspto-grants-2016_05
Patent number
US09340549B2

Reaction notes

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