Sodium Hydroxide → 4-(3-chloro-4-fluorophenyl)-1H-indole

HRID 1839583ノート

反応式

HRID 1839583 の反応式
CC1(C)C(C)(C)OB([C:9]2[CH:17]=[CH:16][CH:15]=[C:14]3[C:10]=2[CH:11]=[CH:12][NH:13]3)O1.Br[C:20]1[CH:25]=[CH:24][C:23]([F:26])=[C:22]([Cl:27])[CH:21]=1.[OH-].[Na+]>C1COCC1.[Pd].C(OCC)(=O)C>[Cl:27][C:22]1[CH:21]=[C:20]([C:9]2[CH:17]=[CH:16][CH:15]=[C:14]3[C:10]=2[CH:11]=[CH:12][NH:13]3)[CH:25]=[CH:24][C:23]=1[F:26]

参加物

7

反応物 3

HCID 14798Sodium HydroxideHCID 35430654-Bromo-2-chloro-1-fluorobenzeneHCID 113224711H-Indole-4-boronic acid, pinacol ester

生成物 1

HCID 225617164-(3-chloro-4-fluorophenyl)-1H-indole収率 70%

試薬・触媒・溶媒 3

HCID 23938Palladium触媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
75 °C

実験手順

To a mixture of 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-indole (3, 3.00 g, 12.34 mmol), and 4-bromo-2-chloro-fluorobenzene (2.58 g, 12.34 mmol) in THF (42 mL)) were added Palladium catalyst Pd(PPh3)4 (0.428 g, 0.37 mmol) and the freshly prepared sodium hydroxide solution (1.50 g, 37.02 mmol in 17 mL water). The system was degassed and then charged with nitrogen. The degas procedure was repeated for three times. The mixture was stirred under nitrogen at 75° C. oil bath for 15 hours. TLC showed the completion of the coupling reaction. The mixture was cooled to room temperature, diluted with ethyl acetate, and separated from water layer. The ethyl acetate solution was washed by brine, dried over Na2SO4, and concentrated. The crude product was purified by a silica gel column eluting with hexanes—EtOAc (9:1) to provide 2.11 g (70%) of the product 4-(3-chloro-4-fluoro-phenyl)-1H-indole as a white solid.

後処理

  1. customThe system was degassed
  2. additioncharged with nitrogen
  3. customthe completion of the coupling reaction
  4. temperatureThe mixture was cooled to room temperature
  5. customseparated from water layer
  6. washThe ethyl acetate solution was washed by brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customThe crude product was purified by a silica gel column
  10. washeluting with hexanes—EtOAc (9:1)

出典と根拠

ORDレコード
ord-5625c202f1af4e1089f58e45cb749c80
出典データセット
uspto-grants-2004_01
特許番号
US06677368B2

反応ノート

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