Bromobenzene → Methyl 5-oxo-1-phenylprolinate

HRID 2238519Notes

Reaction equation

HRID 2238519 reaction equation
[CH2:1]([O:3][C:4](=[O:11])[C@H:5]1[CH2:9][CH2:8][C:7](=[O:10])[NH:6]1)C.Br[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.CO.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:10]=[C:7]1[N:6]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C@H:5]([C:4]([O:3][CH3:1])=[O:11])[CH2:9][CH2:8]1

Participants

8

Reactant 4

HCID 7961BromobenzeneHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 643508ethyl (2R)-5-oxopyrrolidine-2-carboxylate

Product 1

HCID 42260998Methyl 5-oxo-1-phenylprolinateYield 28%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

D-pyroglutamic acid ethyl ester (0.200 g, 1.27 mmol) was dissolved in dioxane (5 ml) and treated with tris(dibenzylideneacetone)dipalladium (0) (0.058 g, 0.06 mmol), bromobenzene (0.351 ml, 1.53 mmol), cesium carbonate (0.621 g, 1.91 mmol) and Xantphos™ (0.110 g, 0.19 mmol). The resulting mixture was heated at reflux overnight and then allowed to cool to room temperature. The mixture was diluted with methanol and filtered. The filtrate was evaporated in vacuo and then partitioned between dichloromethane and saturated aqueous sodium hydrogen carbonate. The aqueous layer was extracted with more dichloromethane (3 aliquots) and then the combined organic layers were washed with brine and dried over magnesium sulphate. Evaporation of the solvent gave a bright yellow residue which was purified by flash silica column chromatography, eluting with a gradient of 0-50% ethyl acetate in hexane, to give methyl 5-oxo-1-phenylprolinate (0.078 g) as a yellow oil. This was used in the next step without further purification.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux overnight
  3. filtrationfiltered
  4. customThe filtrate was evaporated in vacuo
  5. custompartitioned between dichloromethane and saturated aqueous sodium hydrogen carbonate
  6. extractionThe aqueous layer was extracted with more dichloromethane (3 aliquots)
  7. washthe combined organic layers were washed with brine
  8. dry with materialdried over magnesium sulphate
  9. customEvaporation of the solvent
  10. customgave a bright yellow residue which
  11. customwas purified by flash silica column chromatography
  12. washeluting with a gradient of 0-50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-b185d7430c654be7b4c564c1422fe256
Source dataset
uspto-grants-2010_05
Patent number
US07718693B2

Reaction notes

Loading…