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

Temperature

100 °C

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

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)

ORD record

ord-dac4e35d8240483683ba52e10580c318

Source dataset

uspto-grants-2007_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07253198B2