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

HRID 338216

反応式

HRID 338216 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), 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).

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-aa5f4faa416d4dffb0ebe7aebee1bd64
出典データセット
uspto-grants-2014_11
特許番号
US08889730B2

関連ノート

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