Cesium carbonate → Methyl 3-bromo-5-(2-oxopyrrolidin-1-yl)benzoate

HRID 852524Notes

Reaction equation

HRID 852524 reaction equation
[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[C:8](I)[CH:7]=[C:6]([Br:11])[CH:5]=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.[NH:61]1[CH2:65][CH2:64][CH2:63][C:62]1=[O:66]>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].O1CCOCC1>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[C:8]([N:61]2[CH2:65][CH2:64][CH2:63][C:62]2=[O:66])[CH:7]=[C:6]([Br:11])[CH:5]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 120252-PyrrolidoneHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 21942573Methyl 3-bromo-5-iodobenzoate

Product 1

HCID 22253055Methyl 3-bromo-5-(2-oxopyrrolidin-1-yl)benzoateYield 387.5%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
55 °C

Procedure

A flask was charged under nitrogen with 3-bromo-5-iodo-benzoic acid methyl ester (D8a) (14.8 g, 43.4 mmol, 1 equiv), Cs2CO3 (21 g, 65 mmol, 1.5 equiv), tris(dibenzylideneacetone)dipalladium(0) (794 mg, 0.87 mmol, 0.02 equiv), Xantphos (1.5 g, 2.6 mmol, 0.06 equiv) and dioxan (150 ml). Pyrrolidin-2-one (5 ml, 5.54 mmol, 1.5 equiv) was then added via syringe and the resulting mixture was stirred at 55° C. for 5 days then cooled to room temperature and concentrated in vacuo. The residue was partitioned between H2O and AcOEt and the aqueous phase was re-extracted with AcOEt. The combined organic solutions were dried over MgSO4 and concentrated in vacuo to give a solid residue. Purification of the residue by flash chromatography on silica gel (iso-hexane/AcOEt: 4/1 to 1/1) gave 3-bromo-5-(2-oxo-pyrrolidin-1-yl)-benzoic acid methyl ester (D9a) (6.4 g, 50%) as a white solid. [M+H]+=299.9, RT=2.95 min

Workup

  1. temperaturethen cooled to room temperature
  2. concentrationconcentrated in vacuo
  3. customThe residue was partitioned between H2O and AcOEt
  4. extractionthe aqueous phase was re-extracted with AcOEt
  5. dry with materialThe combined organic solutions were dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customto give a solid residue
  8. customPurification of the residue by flash chromatography on silica gel (iso-hexane/AcOEt: 4/1 to 1/1)

Sources & evidence

ORD record
ord-77808bb923564e249f06957260fe16ab
Source dataset
uspto-grants-2007_08
Patent number
US07253198B2

Reaction notes

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