Sodium hydride → 4-Chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-pyrrolo[3,2-c]pyridine

HRID 2278814ノート

反応式

HRID 2278814 の反応式
[Cl:1][C:2]1[C:7]2[CH:8]=[CH:9][NH:10][C:6]=2[CH:5]=[CH:4][N:3]=1.[H-].[Na+].[CH3:13][Si:14]([CH3:21])([CH3:20])[CH2:15][CH2:16][O:17][CH2:18]Cl>O1CCCC1>[Cl:1][C:2]1[C:7]2[CH:8]=[CH:9][N:10]([CH2:18][O:17][CH2:16][CH2:15][Si:14]([CH3:21])([CH3:20])[CH3:13])[C:6]=2[CH:5]=[CH:4][N:3]=1

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 141143844-chloro-1H-pyrrolo[3,2-c]pyridine

生成物 1

HCID 867178114-Chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-pyrrolo[3,2-c]pyridine

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

A mixture of 4-chloro-1H-pyrrolo[3,2-c]pyridine (98%, 2.0 g, 13 mmol) and tetrahydrofuran (20 mL) was cooled to 0° C. Sodium hydride (60% in oil, 1.03 g, 25.8 mmol) was added portion-wise over 5 minutes, and the reaction mixture was allowed to stir at 0° C. for 10 minutes. 2-(Trimethylsilyl)ethoxymethyl chloride (3.40 mL, 19.3 mmol) was then added drop-wise over 5 minutes, and stirring was continued at 0° C. for 15 minutes. The reaction mixture was quenched with saturated aqueous ammonium chloride solution; the aqueous layer was extracted twice with ethyl acetate, and the combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Silica gel chromatography (Gradient: 10% to 20% ethyl acetate in heptane) afforded the product as a colorless oil. Yield: 2.64 g, 9.33 mmol, 72%. LCMS m/z 283.0 [M+H+]. 1H NMR (400 MHz, CDCl3) δ 8.13 (d, J=5.8 Hz, 1H), 7.34 (dd, J=5.8, 0.7 Hz, 1H), 7.25 (d, J=3.3 Hz, 1H), 6.69 (dd, J=3.3, 0.7 Hz, 1H), 5.48 (s, 2H), 3.46 (dd, J=8.2, 8.1 Hz, 2H), 0.89 (dd, J=8.2, 8.1 Hz, 2H), −0.05 (s, 9H).

後処理

  1. stirringstirring
  2. waitwas continued at 0° C. for 15 minutes
  3. customThe reaction mixture was quenched with saturated aqueous ammonium chloride solution
  4. extractionthe aqueous layer was extracted twice with ethyl acetate
  5. dry with materialthe combined organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-d783b55d3206490ca22673073539a436
出典データセット
uspto-grants-2015_09
特許番号
US09133190B2

反応ノート

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