Potassium Carbonate → 4,6-difluoro-5-[4-(3-hydroxyoxetan-3-yl)phenyl]-1H-indole-3-carbaldehyde

HRID 1054622ノート

反応式

HRID 1054622 の反応式
Br[C:2]1[C:3]([F:14])=[C:4]2[C:8](=[CH:9][C:10]=1[F:11])[NH:7][CH:6]=[C:5]2[CH:12]=[O:13].CC1(C)COB([C:22]2[CH:27]=[CH:26][C:25]([C:28]3([OH:32])[CH2:31][O:30][CH2:29]3)=[CH:24][CH:23]=2)OC1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(O)C.C(OCC)(=O)C.[Cl-].[NH4+].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]>[F:14][C:3]1[C:2]([C:22]2[CH:23]=[CH:24][C:25]([C:28]3([OH:32])[CH2:31][O:30][CH2:29]3)=[CH:26][CH:27]=2)=[C:10]([F:11])[CH:9]=[C:8]2[C:4]=1[C:5]([CH:12]=[O:13])=[CH:6][NH:7]2

参加物

9

反応物 3

HCID 11430Potassium CarbonateHCID 866985785-Bromo-4,6-difluoro-1H-indole-3-carbaldehydeHCID 866986243-(4-(5,5-Dimethyl-1,3,2-dioxaborinan-2-yl)phenyl)oxetan-3-ol

生成物 1

HCID 866986254,6-difluoro-5-[4-(3-hydroxyoxetan-3-yl)phenyl]-1H-indole-3-carbaldehyde収率 18%

試薬・触媒・溶媒 5

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 702Ethanol溶媒HCID 1140Toluene溶媒HCID 8857Ethyl Acetate溶媒HCID 25517Ammonium Chloride溶媒

反応条件

温度
110 °C

実験手順

A mixture of 5-bromo-4,6-difluoro-1H-indole-3-carbaldehyde (157 mg, 0.64 mmol), 3-[4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenyl]oxetan-3-ol (190 mg, 0.725 mmol), and 2 M aqueous potassium carbonate (1.2 mL, 2.4 mmol) in toluene (4 mL) and ethanol (2 mL) was degassed with nitrogen for 10 minutes, then treated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (44 mg, 0.06 mmol). The reaction mixture was sealed and heated to for 110° C. for 16 hours. The cooled reaction mixture was diluted with ethyl acetate and ammonium chloride. The layers were separated and the organic layer was washed with brine, dried over sodium sulfate, and concentrated in vacuo. The crude product was purified by flash column chromatography to give the title compound (38 mg).

後処理

  1. customwas degassed with nitrogen for 10 minutes
  2. customThe reaction mixture was sealed
  3. customThe cooled reaction mixture
  4. customThe layers were separated
  5. washthe organic layer was washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by flash column chromatography

出典と根拠

ORDレコード
ord-e4c413846fda4f08b6d1cf54c9d901b7
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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