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Toluene → Methyl 6-chloro-5-(4-(1-hydroxy-2-methylpropan-2-yl)-3-methoxyphenyl)-1H-indole-3-carboxylate

HRID 338381
ノート
印刷プレビュー

反応式

HRID 338381 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:12])([CH3:11])[CH2:9][OH:10])=[C:4]([O:13][CH3:14])[CH:3]=1.[Cl:15][C:16]1[CH:24]=[C:23]2[C:19]([C:20]([C:25]([O:27][CH3:28])=[O:26])=[CH:21][NH:22]2)=[CH:18][C:17]=1B1OCC(C)(C)CO1.C(=O)([O-])[O-].[K+].[K+].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].C1COCC1.O.C(O)C>[Cl:15][C:16]1[CH:24]=[C:23]2[C:19]([C:20]([C:25]([O:27][CH3:28])=[O:26])=[CH:21][NH:22]2)=[CH:18][C:17]=1[C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:12])([CH3:11])[CH2:9][OH:10])=[C:4]([O:13][CH3:14])[CH:3]=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

9

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 866987222-(4-Bromo-2-methoxyphenyl)-2-methylpropan-1-ol2 回

生成物 1

HCID 86698724Methyl 6-chloro-5-(4-(1-hydroxy-2-methylpropan-2-yl)-3-methoxyphenyl)-1H-indole-3-carboxylate収率 56%

試薬・触媒・溶媒 4

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 702Ethanol溶媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
115 °C

実験手順

A mixture of 2-(4-bromo-2-methoxyphenyl)-2-methylpropan-1-ol (crude product from Step 4, containing 40% of the desired material, 75 mg, 0.12 mmol), methyl 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylate (45 mg, 0.14 mmol), PdCl2(dppf) (11 mg, 0.013 mmol), potassium carbonate (80 mg, 0.58 mmol), toluene (0.6 mL), ethanol (0.3 mL), water (0.3 mL), and THF (0.3 mL) was stirred at 115° C. for 2.5 hours. The reaction mixture was cooled to room temperature and extracted with ethyl acetate (4 mL) of ethyl acetate. The extract was loaded on silica gel. Chromatography on a silica gel column, eluting with a gradient from 10% to 40% of ethyl acetate in heptane gave the title compound (25 mg, 56% yield). MS (ES−) 386.2 (M−H)−. Retention time: 3.38 min. Column: Phenomenex Gemini-NX, 4.6 mm×50 mm, C18, 3 μm, 110A; Column Temperature 60° C. Mobile Phase A: 0.1% formic acid in water (v/v); Mobile Phase B: 0.1% formic acid in acetonitrile (v/v) Gradient Profile: Flow-1.5 mL/min. Initial conditions: A-95%, B-5%; Linear Ramp to A-0%, B-100% over 0.0-4.10 min; hold at A-0%, B-100% from 4.10-4.50 min; return to initial conditions 4.60-5.0 min.

後処理

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted with ethyl acetate (4 mL) of ethyl acetate
  3. washChromatography on a silica gel column, eluting with a gradient from 10% to 40% of ethyl acetate in heptane

出典と根拠

ORDレコード
ord-131eb00d5cb14089b89f4207890faca5
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

読み込み中…

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