Cesium carbonate → Methyl 4-(2-oxopyrrolidin-1-yl)benzoate

HRID 1093845Notes

Reaction equation

HRID 1093845 reaction equation
[NH:1]1[CH2:5][CH2:4][CH2:3][C:2]1=[O:6].[CH3:7][O:8][C:9](=[O:17])[C:10]1[CH:15]=[CH:14][C:13](Br)=[CH:12][CH:11]=1.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.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.[Pd].[Pd]>[CH3:7][O:8][C:9](=[O:17])[C:10]1[CH:15]=[CH:14][C:13]([N:1]2[CH2:5][CH2:4][CH2:3][C:2]2=[O:6])=[CH:12][CH:11]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 120252-PyrrolidoneHCID 12081Methyl 4-bromobenzoateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)

Product 1

HCID 757827Methyl 4-(2-oxopyrrolidin-1-yl)benzoateYield 37.89%

Reagents, catalysts & solvents 2

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

Procedure

A mixture of pyrrolidin-2-one (500 mg, 5.9 mmol), 4-bromo benzoic acid methyl ester (1.5 g, 6.97 mmol), Pd2(dba)3 (135 mg, 0.14 mmol), xantphos (256 mg, 0.44 mmol) and cesium carbonate (2.7 g, 8.28 mmol) in dioxane (2 mL) in a sealed tube was subjected to reaction in a microwave reactor (time: 20 min, temp: 105° C., power: zero). The reaction mixture was filtered through celite and the filtrate collected was concentrated under reduced pressure. The residue was diluted with cold water, extracted with ethyl acetate, dried over sodium sulfate and concentrated under reduced pressure to afford the residue. The residue obtained was purified by column chromatography (using 60-120 silica gel and 50% ethyl acetate in hexane as eluent) to afford 485 mg (37.89% Yield) of 4-(2-oxo-pyrrolidin-1-yl)-benzoic acid methyl ester. NaOH (295 mg, 7.4 mmol) was added to a stirred mixture of 4-(2-oxo-pyrrolidin-1-yl)-benzoic acid methyl ester (485 mg, 2.2 mmol) in a mixture of MeOH (5 mL) and H2O (5 mL), stirring was continued at 60° C. for 1 hr. After completion of the reaction, the reaction mixture was concentrated under reduced pressure to get the residue, which was acidified with 10% aqueous HCl solution, the precipitate was collected to afford 300 mg (66% Yield) of 4-(2-oxo-pyrrolidin-1-yl)-benzoic acid.

Workup

  1. customwas subjected to reaction in a microwave reactor (time: 20 min, temp: 105° C., power: zero)
  2. filtrationThe reaction mixture was filtered through celite
  3. customthe filtrate collected
  4. concentrationwas concentrated under reduced pressure
  5. additionThe residue was diluted with cold water
  6. extractionextracted with ethyl acetate
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customto afford the residue
  10. customThe residue obtained
  11. customwas purified by column chromatography (using 60-120 silica gel and 50% ethyl acetate in hexane as eluent)

Sources & evidence

ORD record
ord-682fa6fa7bd44eea969cc67b468c2b83
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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