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

HRID 1054561ノート

反応式

HRID 1054561 の反応式
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

参加物

9

反応物 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

生成物 1

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

試薬・触媒・溶媒 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 702Ethanol溶媒HCID 962Water溶媒HCID 1140Toluene溶媒

反応条件

温度
110 °C

実験手順

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), 2 M 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., 1 H), 9.91 (s, 1 H), 8.35 (s, 1 H), 8.02 (s, 1 H), 7.67 (s, 1 H), 7.54 (d, J=8.00 Hz, 2 H), 7.38 (d, J=8.20 Hz, 2 H), 5.50 (s, 1 H), 2.36-2.45 (m, 2 H), 2.22-2.33 (m, 2 H), 1.92 (m, 1 H), 1.61-1.71 (m, 1 H).

後処理

  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)

出典と根拠

ORDレコード
ord-7bf00f19d43c4abb92f38d6b5a309127
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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