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

HRID 852641
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HRID 852641 반응식
[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
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참가 물질

9

반응물 4

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

생성물 1

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

시약·촉매·용매 4

HCID 9811564
Bis(dibenzylideneacetone)palladium
촉매
HCID 962Water용매
HCID 80711,2-Dimethoxyethane용매
HCID 8857Ethyl Acetate용매

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온도
100 °C

실험 절차

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

후처리

  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)

출처 및 근거

ORD 기록
ord-dac4e35d8240483683ba52e10580c318
출처 데이터셋
uspto-grants-2007_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07253198B2

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