Toluene → 6-chloro-5-[4-(3-hydroxypropoxy)phenyl]-1H-indole-3-carbaldehyde

HRID 1054645ノート

反応式

HRID 1054645 の反応式
CC1(C)COB([C:8]2[CH:18]=[CH:17][C:11]([O:12][CH2:13][CH2:14][CH2:15][OH:16])=[CH:10][CH:9]=2)OC1.Br[C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][C:29]=1[Cl:30])[NH:26][CH:25]=[C:24]2[CH:31]=[O:32].C1(C)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+]>C(O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:30][C:29]1[CH:28]=[C:27]2[C:23]([C:24]([CH:31]=[O:32])=[CH:25][NH:26]2)=[CH:22][C:21]=1[C:8]1[CH:9]=[CH:10][C:11]([O:12][CH2:13][CH2:14][CH2:15][OH:16])=[CH:17][CH:18]=1

参加物

7

反応物 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 866985665-bromo-6-chloro-1H-indole-3-carbaldehydeHCID 866986443-(4-(5,5-Dimethyl-1,3,2-dioxaborinan-2-yl)phenoxy)propan-1-ol2 回

生成物 1

HCID 866986486-chloro-5-[4-(3-hydroxypropoxy)phenyl]-1H-indole-3-carbaldehyde収率 44.5%

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 702Ethanol溶媒2 回

反応条件

温度
100 °C

実験手順

To a solution of 3-[4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenoxy]propan-1-ol (4.9 g, 18.6 mmol) in ethanol (25 ml) was added 5-bromo-6-chloro-1H-indole-3-carbaldehyde (4.0 g, 15 mmol) followed by toluene (50 ml) and 2 N aq. potassium carbonate (26.3 ml, 52.6 mmol). Nitrogen was bubbled though the solution for 15 min, then Pd(dppf)Cl2 (0.46 g, 0.62 mol) was added and reaction heated to 100° C. An additional portion of 3-[4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenoxy]propan-1-ol (1.0 g) in ethanol (4 ml) was added and heating continued for 30 min. The reaction was allowed to cool to room temperature and stirred for 3 days. The reaction was partitioned between water and EtOAc and stirred. The layers were separated and the organic layers were washed with water which resulted in a thick emulsion. The emulsion was filtered through celite to attempt to break the emulsion which had limited effect. Upon standing, emulsion was reduced. Layers were separated and organic washed with brine, dried over sodium sulfate, filtered and stripped. Residue was mostly dissolved in MeOH, filtered to remove solids then adsorbed onto silica gel then purified by silica gel chromatography (30-100% EtOAc/Heptane). The second peak was isolated to afford the title compound (2.2 g, 43%) as a yellow solid that was taken on to the next reaction without further purification.

後処理

  1. customNitrogen was bubbled though the solution for 15 min
  2. customreaction
  3. temperatureheating
  4. temperatureto cool to room temperature
  5. customThe reaction was partitioned between water and EtOAc
  6. stirringstirred
  7. customThe layers were separated
  8. washthe organic layers were washed with water which
  9. customresulted in a thick emulsion
  10. filtrationThe emulsion was filtered through celite
  11. customLayers were separated
  12. washorganic washed with brine
  13. dry with materialdried over sodium sulfate
  14. filtrationfiltered
  15. dissolutionResidue was mostly dissolved in MeOH
  16. filtrationfiltered
  17. customto remove solids
  18. customthen purified by silica gel chromatography (30-100% EtOAc/Heptane)
  19. customThe second peak was isolated

出典と根拠

ORDレコード
ord-f7e22fb9fcc54adfb7817bdca0152034
出典データセット
uspto-grants-2016_07
特許番号
US09394285B2

反応ノート

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