Sodium hydride → 7-bromo-5-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indole-3-carbonitrile

HRID 913966

反応式

HRID 913966 の反応式
[H-].[Na+].[Br:3][C:4]1[CH:5]=[C:6]([Cl:15])[CH:7]=[C:8]2[C:12]=1[NH:11][CH:10]=[C:9]2[C:13]#[N:14].[CH3:16][Si:17]([CH3:24])([CH3:23])[CH2:18][CH2:19][O:20][CH2:21]Cl>C1COCC1>[Br:3][C:4]1[CH:5]=[C:6]([Cl:15])[CH:7]=[C:8]2[C:12]=1[N:11]([CH2:21][O:20][CH2:19][CH2:18][Si:17]([CH3:24])([CH3:23])[CH3:16])[CH:10]=[C:9]2[C:13]#[N:14]

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 575462207-bromo-5-chloro-1H-indole-3-carbonitrile

生成物 1

HCID 575460027-bromo-5-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indole-3-carbonitrile収率 95.5%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

Sodium hydride (0.081 g, 2.020 mmol) (60% in oil) was added slowly to a 0° C. solution of 7-bromo-5-chloro-1H-indole-3-carbonitrile (0.43 g, 1.683 mmol) in THF (10 mL). Bubbling occurred, and the reaction was stirred at 0° C. for 30 min, then 2-(Trimethylsilyl)ethoxymethyl chloride (0.418 mL, 2.356 mmol) was added. After stirring 30 min at ambient temperature, the reaction was quenched with aqueous sodium bicarbonate (10 mL) and extracted with ethyl acetate (2×20 mL). The organic layer was dried with MgSO4 and evaporated, and the residue was purified by chromatography on SiO2 with 5% ethyl acetate/hexanes to give 7-bromo-5-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indole-3-carbonitrile (620 mg, 1.607 mmol, 95% yield) as a yellow solid. 1H-NMR (CDCl3, 400 MHz) δ 7.71 (s, 1H), 7.69 (d, J=2.0 Hz, 1H), 7.53 (d, J=2.0 Hz, 1H), 5.82 (s, 2H), 3.52 (app T, J=8.1 Hz, 2H), 0.90 (app t, J=8.2 Hz, 2H), −0.05 (s, 9H). LC/MS (HPLC method 4): tR=4.07 min, 385.4(MH)+.

後処理

  1. customBubbling
  2. stirringAfter stirring 30 min at ambient temperature
  3. customthe reaction was quenched with aqueous sodium bicarbonate (10 mL)
  4. extractionextracted with ethyl acetate (2×20 mL)
  5. dry with materialThe organic layer was dried with MgSO4
  6. customevaporated
  7. customthe residue was purified by chromatography on SiO2 with 5% ethyl acetate/hexanes

出典と根拠

ORDレコード
ord-c1399958c54a4df4916a36b288e0bdbf
出典データセット
uspto-grants-2011_09
特許番号
US08026257B2

関連ノート

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