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

HRID 1054622노트

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HRID 1054622 반응식
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

참가 물질

9

반응물 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

생성물 1

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

시약·촉매·용매 5

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 702Ethanol용매HCID 1140Toluene용매HCID 8857Ethyl Acetate용매HCID 25517Ammonium Chloride용매

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온도
110 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-e4c413846fda4f08b6d1cf54c9d901b7
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09394285B2

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