Ethanol → 6-fluoro-5-[4-(hydroxymethyl)phenyl]-1H-indole-3-carbaldehyde

HRID 338233노트

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HRID 338233 반응식
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[F:11])[NH:7][CH:6]=[C:5]2[CH:12]=[O:13].[OH:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19](B(O)O)=[CH:18][CH:17]=1.C(O)C.C(=O)([O-])[O-].[K+].[K+]>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].C1(C)C=CC=CC=1>[F:11][C:10]1[CH:9]=[C:8]2[C:4]([C:5]([CH:12]=[O:13])=[CH:6][NH:7]2)=[CH:3][C:2]=1[C:19]1[CH:20]=[CH:21][C:16]([CH2:15][OH:14])=[CH:17][CH:18]=1

참가 물질

7

반응물 4

HCID 702EthanolHCID 11430Potassium CarbonateHCID 27347064-(Hydroxymethyl)benzeneboronic acidHCID 735543615-Bromo-6-fluoro-1H-indole-3-carbaldehyde

생성물 1

HCID 866985806-fluoro-5-[4-(hydroxymethyl)phenyl]-1H-indole-3-carbaldehyde수율 58.4%

시약·촉매·용매 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 1140Toluene용매

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온도
90 °C

실험 절차

A mixture of 5-bromo-6-fluoro-1H-indole-3-carbaldehyde (100 mg, 0.413 mmol), [4-(hydroxymethyl)phenyl]boronic acid (69 mg, 0.454 mmol), ethanol (1.04 mL), toluene (1.0 mL) and 2M aqueous potassium carbonate (0.824 mL, 1.65 mmol) were deoxygenated with nitrogen. [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium (II) (25 mg, 0.033 mmol) was added and the reaction mixture was deoxygenated with nitrogen for 2 more minutes. The reaction mixture was sealed and heated at 90° C. for 16 hours. After cooling to room temperature, the phases were separated, and the aqueous phase was diluted with water and extracted twice with ethyl acetate. The combined organic layers were concentrated in vacuo and purified using silica gel chromatography (1:3 to 3:1 ethyl acetate/heptanes) to give the title compound (65 mg). MS (ES−) 268.2 (M−H)−.

후처리

  1. customwere deoxygenated with nitrogen
  2. customthe reaction mixture was deoxygenated with nitrogen for 2 more minutes
  3. customThe reaction mixture was sealed
  4. temperatureAfter cooling to room temperature
  5. customthe phases were separated
  6. additionthe aqueous phase was diluted with water
  7. extractionextracted twice with ethyl acetate
  8. concentrationThe combined organic layers were concentrated in vacuo
  9. custompurified

출처 및 근거

ORD 기록
ord-4432b2d3fb58470a90cd8fe59b306bee
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08889730B2

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