Potassium Carbonate → 4,6-difluoro-5-{4-[1-(hydroxymethyl)cyclopropyl]phenyl}-1H-indole-3-carbaldehyde

HRID 1054627ノート

反応式

HRID 1054627 の反応式
Br[C:2]1[C:3]([F:14])=[C:4]2[C:8](=[CH:9][C:10]=1[F:11])[NH:7][CH:6]=[C:5]2[CH:12]=[O:13].CC1(C)COB([C:22]2[CH:27]=[CH:26][C:25]([C:28]3([CH2:31][OH:32])[CH2:30][CH2:29]3)=[CH:24][CH:23]=2)OC1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.CCO.O.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]>[F:14][C:3]1[C:2]([C:22]2[CH:27]=[CH:26][C:25]([C:28]3([CH2:31][OH:32])[CH2:29][CH2:30]3)=[CH:24][CH:23]=2)=[C:10]([F:11])[CH:9]=[C:8]2[C:4]=1[C:5]([CH:12]=[O:13])=[CH:6][NH:7]2

参加物

8

反応物 3

HCID 11430Potassium CarbonateHCID 866985785-Bromo-4,6-difluoro-1H-indole-3-carbaldehydeHCID 86698629(1-(4-(5,5-Dimethyl-1,3,2-dioxaborinan-2-yl)phenyl)cyclopropyl)methanol

生成物 1

HCID 866986304,6-difluoro-5-{4-[1-(hydroxymethyl)cyclopropyl]phenyl}-1H-indole-3-carbaldehyde収率 28%

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

実験手順

A solution of 5-bromo-4,6-difluoro-1H-indole-3-carbaldehyde (200 mg, 0.77 mmol) and {1-[4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenyl]cyclopropyl}methanol (200 mg, 0.77 mmol) in toluene (6 mL) and EtOH (2 mL) was added a solution of potassium carbonate (318 mg, 2.31 mmol) in water (1.0 mL) and Pd(dppf)Cl2 (31 mg, 0.04 mmol) at room temperature under N2. The reaction was cooled to room temperature, and extracted with ethyl acetate (20 mL×3). The organic layers were washed with brine (20 mL), dried over sodium sulfate, concentrated, and purified by column chromatography to give the title compound (70 mg, 28%) as a yellow solid. 1H NMR (400 MHz, CD3OD) δ 10.00 (s, 1 H), 8.12 (s, 1 H), 7.49 (d, 2 H), 7.40 (d, 2 H), 7.19 (d, 1 H), 3.69 (s, 2 H), 0.89 (s, 4 H).

後処理

  1. extractionextracted with ethyl acetate (20 mL×3)
  2. washThe organic layers were washed with brine (20 mL)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. custompurified by column chromatography

出典と根拠

ORDレコード
ord-4e9eaac2dec14627ad99f5ab60156e48
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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