Potassium Carbonate → 6-Chloro-5-(4-hydroxymethyl-phenyl)-1H-indole-3-carbaldehyde

HRID 338219

반응식

HRID 338219 반응식
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[Cl: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)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.CCO.CCOC(C)=O.CCOC(C)=O.CCCCCCC.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: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

9

반응물 3

HCID 11430Potassium CarbonateHCID 27347064-(Hydroxymethyl)benzeneboronic acidHCID 866985665-bromo-6-chloro-1H-indole-3-carbaldehyde

생성물 1

HCID 866985706-Chloro-5-(4-hydroxymethyl-phenyl)-1H-indole-3-carbaldehyde수율 20%

시약·촉매·용매 5

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 702Ethanol용매HCID 1140Toluene용매HCID 8857Ethyl Acetate용매HCID 21899848Ethylacetate heptane용매

반응 조건

온도
120 °C

실험 절차

A mixture of 5-bromo-6-chloro-1H-indole-3-carbaldehyde (783 mg, 3.03 mmol), 4-(hydroxymethyl)benzene boronic acid (460 mg, 3.03 mmol), 2N aqueous potassium carbonate (6.4 mL, 13 mmol) in toluene (9 mL) and EtOH (13 mL) was degassed with N2 for 5 minutes, then treated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (247 mg, 0.30 mmol). The mixture was heated in a sealed tube to 120° C. and stirred for 2.5 hours. The reaction mixture was cooled to room temperature, diluted with EtOAc (200 mL), then washed with water (50 mL) and brine (50 mL). The organic layer was dried over MgSO4 and concentrated in vacuo. The resulting brown foam was purified by flash chromatography (20-100% EtOAc/heptane) to afford a pale yellow solid. The solid was dissolved in 5:1 EtOAc/heptane (30 mL), and a colorless precipitate formed. The precipitate was collected by filtration, washed with heptane and dried under vacuum to afford the title compound (173 mg, 20% yield) as a colorless solid. MS (ES+) 286.0 (M+H)+. 1H NMR (500 MHz, CD3OD) δ 9.92 (s, 1H) 8.07 (s, 1H) 8.25 (s, 1H) 7.64 (s, 1H) 7.44 (m, 4H) 4.70 (s, 2H).

후처리

  1. customwas degassed with N2 for 5 minutes
  2. temperatureThe reaction mixture was cooled to room temperature
  3. washwashed with water (50 mL) and brine (50 mL)
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe resulting brown foam was purified by flash chromatography (20-100% EtOAc/heptane)
  7. customto afford a pale yellow solid
  8. customa colorless precipitate formed
  9. filtrationThe precipitate was collected by filtration
  10. washwashed with heptane
  11. customdried under vacuum

출처 및 근거

ORD 기록
ord-f76aa54d9f294fed941559c9d9058359
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08889730B2

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