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

HRID 338216

반응식

HRID 338216 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].CC1(C)COB([C:21]2[CH:26]=[CH:25][C:24]([C:27]3([OH:31])[CH2:30][CH2:29][CH2:28]3)=[CH:23][CH:22]=2)OC1.C(=O)([O-])[O-].[K+].[K+].[NH4+].[Cl-]>CCO.C1(C)C=CC=CC=1.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].O>[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:21]1[CH:26]=[CH:25][C:24]([C:27]2([OH:31])[CH2:30][CH2:29][CH2:28]2)=[CH:23][CH:22]=1

참가 물질

9

반응물 4

HCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 866985665-bromo-6-chloro-1H-indole-3-carbaldehydeHCID 866985671-(4-(5,5-Dimethyl-1,3,2-dioxaborinan-2-yl)phenyl)cyclobutanol

생성물 1

HCID 866985686-Chloro-5-(4-(1-hydroxycyclobutyl)phenyl)-1H-indole-3-carbaldehyde수율 64.2%

시약·촉매·용매 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 702Ethanol용매HCID 962Water용매HCID 1140Toluene용매

반응 조건

온도
110 °C

실험 절차

A mixture of 5-bromo-6-chloro-1H-indole-3-carbaldehyde (6.15 g, 23.8 mmol), 1-[4-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)-phenyl]-cyclobutanol (8.35 g, 32.1 mmol), 2M aqueous potassium carbonate (47.5 mL, 95.0 mmol) in EtOH (33 mL) and toluene (86 mL) was degassed with N2 for 25 minutes, then treated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (1.93 g, 2.64 mmol). The reaction mixture was heated to 110° C. and stirred for 2 hours. The reaction mixture was cooled to room temperature, poured into a 3:1 mixture of saturated aqueous NH4Cl solution/water (450 mL) and extracted with EtOAc (10×150 mL), followed by 9:1 CH2Cl2/i-PrOH (4×100 mL). The combined organic layers were dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (0-100% EtOAc/heptane, with 0.03% formic acid modifier) to afford the title compound (4.98 g, 64%) as a red solid. MS (ES+) 326.5 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ 12.21 (br. s., 1H), 9.91 (s, 1H), 8.35 (s, 1H), 8.02 (s, 1H), 7.67 (s, 1H), 7.54 (d, J=8.00 Hz, 2H), 7.38 (d, J=8.20 Hz, 2H), 5.50 (s, 1H), 2.36-2.45 (m, 2H), 2.22-2.33 (m, 2H), 1.92 (m, 1H), 1.61-1.71 (m, 1H).

후처리

  1. customwas degassed with N2 for 25 minutes
  2. temperatureThe reaction mixture was cooled to room temperature
  3. extractionextracted with EtOAc (10×150 mL)
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by flash chromatography (0-100% EtOAc/heptane, with 0.03% formic acid modifier)

출처 및 근거

ORD 기록
ord-aa5f4faa416d4dffb0ebe7aebee1bd64
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08889730B2

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