Aniline → 3-(2-Oxo-pyrrolidin-1-yl)-5-phenylamino-benzoic acid methyl ester

HRID 852641Notes

Reaction equation

HRID 852641 reaction equation
[CH3:1][O:2][C:3](=[O:17])[C:4]1[CH:9]=[C:8]([N:10]2[CH2:14][CH2:13][CH2:12][C:11]2=[O:15])[CH:7]=[C:6](Br)[CH:5]=1.C([O-])([O-])=O.[Cs+].[Cs+].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.[NH2:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1>O.CCOC(C)=O.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].COCCOC>[CH3:1][O:2][C:3](=[O:17])[C:4]1[CH:5]=[C:6]([NH:45][C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[CH:7]=[C:8]([N:10]2[CH2:14][CH2:13][CH2:12][C:11]2=[O:15])[CH:9]=1

Participants

9

Reactant 4

HCID 6115AnilineHCID 10796Cesium carbonateHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 22253055Methyl 3-bromo-5-(2-oxopyrrolidin-1-yl)benzoate

Product 1

HCID 693601083-(2-Oxo-pyrrolidin-1-yl)-5-phenylamino-benzoic acid methyl esterYield 32.2%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A flask was charged under nitrogen with 3-bromo-5-(2-oxo-pyrrolidin-1-yl)-benzoic acid methyl ester (D9a) (298 mg, 1 mmol, 1 equiv), Cs2CO3 (488 mg, 1.5 mmol, 1.5 equiv), tris(dibenzylideneacetone)dipalladium(0) (18.3 mg, 0.02 mmol, 0.02 equiv), 2-(di-tert-butylphosphino)biphenyl (18 mg, 0.06 mmol, 0.06 equiv) and DME (8 ml). Aniline (136 μl, 1.5 mmol, 1.5 equiv) was then added via syringe and the resulting mixture was stirred at 100° C. for 16 h then cooled to room temperature, diluted with H2O and AcOEt. The layers were separated and the aqueous phase was extracted with AcOEt. The combined organic phases were dried over MgSO4 and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (iso-hexane/AcOEt: 3/1 to 1/1) gave 3-(2-oxo-pyrrolidin-1-yl)-5-phenylamino-benzoic acid methyl ester (B30) (100 mg, 32%) as a white solid. [M+H]+=311.0, RT=3.14 min

Workup

  1. temperaturethen cooled to room temperature
  2. customThe layers were separated
  3. extractionthe aqueous phase was extracted with AcOEt
  4. dry with materialThe combined organic phases were dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customPurification of the residue by flash chromatography on silica gel (iso-hexane/AcOEt: 3/1 to 1/1)

Sources & evidence

ORD record
ord-dac4e35d8240483683ba52e10580c318
Source dataset
uspto-grants-2007_08
Patent number
US07253198B2

Reaction notes

Loading…