2,4-Difluoroaniline → [2-Chloro-4-(2,4-difluoro-phenylamino)-phenyl]-(2-fluoro-5-hydroxy-phenyl)-methanone

HRID 1012655

반응식

HRID 1012655 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[CH:15]=[C:14]([OH:16])[CH:13]=[CH:12][C:11]=2[F:17])=[O:9])=[C:4]([Cl:18])[CH:3]=1.[F:19][C:20]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=1[NH2:27].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.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]>[Cl:18][C:4]1[CH:3]=[C:2]([NH:27][C:21]2[CH:22]=[CH:23][C:24]([F:26])=[CH:25][C:20]=2[F:19])[CH:7]=[CH:6][C:5]=1[C:8]([C:10]1[CH:15]=[C:14]([OH:16])[CH:13]=[CH:12][C:11]=1[F:17])=[O:9]

참가 물질

7

반응물 4

HCID 97092,4-DifluoroanilineHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 67314566(4-Bromo-2-chloro-phenyl)-(2-fluoro-5-hydroxy-phenyl)-methanone

생성물 1

HCID 67314403[2-Chloro-4-(2,4-difluoro-phenylamino)-phenyl]-(2-fluoro-5-hydroxy-phenyl)-methanone

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

반응 조건

온도
130 °C

실험 절차

Compound 511 (200 mg, 0.6 mmol) was dissolved in dry 1,4-dioxane (5 mL) in a reaction vial under an argon atmosphere. 2,4-Difluoro-phenylamine (78 mg, 62 μL, 0.6 mmol) was added and dissolved in the solvent. Rac-BINAP (17 mg, 0.028 mmol), Pd2(dba)3 (17 mg, 0.018 mmol) and Cs2CO3 (277 mg, 0.85 mmol) were added. The reaction vial was flushed with argon, closed and then stirred at 130° C. for 40 min. In a microwave oven. The reaction mixture was allowed to cool to RT, filtered through Celite and then purified by continuous gradient flash chromatography using EtOAc/petroleum ether (40-60)(v:v=1:7 to 1:3) as the eluent to afford the title compound as a yellow solid.

후처리

  1. dissolutiondissolved in the solvent
  2. customThe reaction
  3. customvial was flushed with argon
  4. customclosed
  5. temperatureto cool to RT
  6. filtrationfiltered through Celite
  7. custompurified by continuous gradient flash chromatography

출처 및 근거

ORD 기록
ord-f9dc97f4ae224e29868f362446c62f46
출처 데이터셋
uspto-grants-2011_07
특허 번호
US07977387B2

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