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Toluene → methyl 6-chloro-5-[4-(1-hydroxy-cyclobutyl)-3-methoxy-phenyl]-1H-indole-3-carboxylate

HRID 338369
ノート
印刷プレビュー

反応式

HRID 338369 の反応式
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([O:13][CH3:14])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1B1OCC(C)(C)CO1.Br[C:24]1[CH:29]=[CH:28][C:27]([C:30]2([OH:34])[CH2:33][CH2:32][CH2:31]2)=[CH:26][C:25]=1OC.[C:37](=O)([O-])[O-:38].[K+].[K+].C1(C)C=CC=CC=1>C(OCC)(=O)C.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].ClCCl.C(O)C>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([O:13][CH3:14])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:24]1[CH:25]=[CH:26][C:27]([C:30]2([OH:34])[CH2:31][CH2:32][CH2:33]2)=[C:28]([O:38][CH3:37])[CH:29]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

8

反応物 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 86698665methyl 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylateHCID 866987131-(4-Bromo-3-methoxyphenyl)cyclobutanol

生成物 1

HCID 86698712methyl 6-chloro-5-[4-(1-hydroxy-cyclobutyl)-3-methoxy-phenyl]-1H-indole-3-carboxylate収率 32%

試薬・触媒・溶媒 3

HCID 178418807HCID 178418807、化合物触媒HCID 702Ethanol溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
100 °C

実験手順

A mixture of methyl 6-Chloro-5-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)-1H-indole-3-carboxylate (50 mg, 0.16 mmol), 1-(4-Bromo-3-methoxy-phenyl)cyclobutanol (52 mg, 0.2 mmol), 2M aqueous potassium carbonate (0.31 mL, 0.63 mmol), toluene (3 mL), and ethanol (1 mL) was sparged with nitrogen for 10 minutes, then treated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane adduct (6 mg, 0.007 mmol). The reaction mixture was heated to 100° C. and stirred. After 2 hours the reaction was cooled to room temperature, diluted with ethyl acetate, washed with water and saturated brine, dried over magnesium sulfate, filtered and concentrated in vacuo to afford a yellow oil, which was purified by flash chromatography (12 g silica, 0-35% ethyl acetate/heptane, 24 column volumes). Product fractions were combined and concentrated in vacuo to afford the title compound as a colorless solid (19 mg, 32% yield). MS (ES−) 341.2 (M−H)−; 1H NMR (500 MHz, CD3OD) δ 8.03 (d, J=1.95 Hz, 2H), 7.60 (s, 1H), 7.38 (d, J=7.56 Hz, 1H), 7.06 (d, J=1.46 Hz, 1H), 7.01 (dd, J=7.68, 1.59 Hz, 1H), 3.89 (d, J=7.32 Hz, 6H), 2.65-2.75 (m, 2H), 2.34-2.44 (m, 2H), 2.08-2.19 (m, 1H), 1.70-1.80 (m, 1H).

後処理

  1. customwas sparged with nitrogen for 10 minutes
  2. temperatureAfter 2 hours the reaction was cooled to room temperature
  3. washwashed with water and saturated brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto afford a yellow oil, which
  8. customwas purified by flash chromatography (12 g silica, 0-35% ethyl acetate/heptane, 24 column volumes)
  9. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-ca54f1640f544d9f93178953f7c123b4
出典データセット
uspto-grants-2014_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08889730B2

反応ノート

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